Immunogenicity of the 23-Valent Polysaccharide Pneumococcal Vaccine in Children with Idiopathic Nephrotic Syndrome

Immunogenicity of the 23-Valent Polysaccharide Pneumococcal Vaccine in Children with Idiopathic Nephrotic Syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Immunogenicity of the 23-Valent Polysaccharide Pneumococcal Vaccine in Children with Idiopathic Nephrotic Syndrome Ersin Ulu, Salim Calışkan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6933268/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Nov, 2025 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Background Due to secondary immunodeficiency, idiopathic nephrotic syndrome in children increases the risk of invasive pneumococcal disease. This study compares pneumococcal vaccine antibody responses in children with idiopathic nephrotic syndrome to healthy controls. We also investigated the effects of relapse frequency and corticosteroid dose on antibody levels in children with idiopathic nephrotic syndrome. Methods The study included 30 children with corticosteroid-responsive minimal change nephrotic syndrome and 24 healthy children. All children participating in the study were vaccinated with the 23-valent pneumococcal polysaccharide vaccine. Results Positive vaccine response (at least a 2-fold increase in polysaccharide anti-pneumococcal IgG titers) rates and the titer change rates were similar between patients and healthy subjects. Moreover, the rates of a four-fold increase were comparable between the two groups. Additionally, relapse rate and corticosteroid doses in patients did not impact pre- and post-vaccination antibody titers. No adverse events were observed during the study. Conclusions The 23-valent pneumococcal polysaccharide vaccine is safe and elicits a robust immune response in children with idiopathic nephrotic syndrome, comparable to that of healthy children. The response also was unaffected by disease relapses or cumulative corticosteroid dose. Larger cohorts and antibody protection duration are needed for the vaccine response investigation. Children Idiopathic nephrotic syndrome Pneumococcal infection Vaccination Immunogenicity Figures Figure 1 Introduction Idiopathic nephrotic syndrome (INS) is the most common chronic kidney disease in pediatric populations. Immune dysregulation plays a significant role in its pathophysiology. Thanks to the effective use of antibiotics and corticosteroids, the mortality rate of children with nephrotic syndrome (NS) has decreased to less than 5% in recent years. The most common subtype of INS in childhood, known as steroid-responsive/sensitive nephrotic syndrome (SSNS), responds well to corticosteroid treatment. However, SSNS is a recurrent disease in a significant number of patients, with two-thirds of cases relapsing after initial treatment. Recurrent relapses are associated with higher morbidity. Infections, particularly invasive pneumococcal disease (IPD), could play a role in triggering the relapse [1] An acquired immune deficiency in INS predisposes individuals to IPD. Many factors have been demonstrated to exert a deleterious effect on the immune system in INS, and these may be present concurrently at different stages of the disease. Previously, it was thought that T cell-dependent immune dysregulation was the primary cause of the disease. Recent evidence indicates that podocyte-related disorders and even B-cell disorders may also play a significant role [2,3]. A notable depletion of immunoglobulins in the urine is observed during the initial stages of the disease and the recurring relapses [4]. Corticosteroid usage in the treatment may also contribute to the immunosuppression related to disease per se. As a result, the decreased immunoglobulin levels, widespread protein deficiency, impaired opsonization, and reduced spleen function observed in NS patients make them susceptible to infections. Additionally, components of the alternative complement pathway, such as factors B and D, are lost in the urine. This loss causes a lack of opsonization of encapsulated microorganisms, including Pneumococci and Escherichia coli . Peritonitis, cellulitis, and sepsis caused by encapsulated microorganisms, particularly Pneumococci, are more common in these patients [5,6,7]. Children with INS are at an elevated risk for developing invasive pneumococcal disease (IPD). Vaccinating INS patients with the polysaccharide pneumococcal vaccine has been recommended for several years to protect them from IPD [8,9]. However, the acquired immunodeficiency in INS has elicited concerns on the immunogenicity of the patients to this vaccine. Consequently, antibody responses to pneumococcal vaccines have been investigated in children with INS [10]. Previously, antibody responses to 14-valent and lower-valent PPV in children with INS were as satisfactory as it was in the healthy control group[11,12]. Following the extensive implementation of the 14-valent vaccine, epidemiological investigations in the general population have demonstrated a reduction in the incidence of IPD attributable to the serotypes included in this vaccine. In contrast, the number of IPD associated with the serotypes not included in this vaccine has increased over time. Nevertheless, the number of serotypes responsible for IPD has increased over time, reaching over 100 capsular serotypes of Streptococcus Pneumoniae [13,14]. A novel PPV vaccine comprising 23 pneumococcal serotypes, the most prevalent cause of IPD, was introduced in 1983. However, polysaccharide pneumococcal vaccines (PPV) were only capable of eliciting an immune response after the age of two. Although conjugate pneumococcal vaccines are effective in children under 2 years of age, they contain fewer serotypes than the 23-valent PPV. Since the conjugate vaccines administered during infancy provide partial protection, the current guidelines recommend at least one dose of PPV23 after 2 years of age for high-risk groups. The objective of this study is to evaluate the immunogenicity of PPV23 in children with SSNS in comparison to healthy controls. Furthermore, the study aims to investigate the influence of the frequency of disease relapse and cumulative corticosteroid doses on antibody levels at the baseline and the 6 th week of vaccination in children with SSNS. Methods Study Design and Subjects : The study was approved by the local ethics committee of Istanbul University-Cerrahpaşa (formerly Istanbul University), Cerrahpaşa Faculty of Medicine (No: 3248). Only those who provided informed consent were included in the study. Individuals with a history of hypersensitivity to any vaccine were excluded. None of the participants had received any pneumococcal vaccine before the study. Patients with a diagnosis of minimal change nephrotic syndrome who were regularly followed up in the department of pediatric nephrology and who were responsive to corticosteroid therapy were enrolled in the study. A total of 30 children, comprising 10 boys and 20 girls, were included in the SSNS group. The subjects were all older than two years of age, ranging from 2.7 years to 15.5 years (mean age: 8.40 ± 3.51 years). No patients had any chronic infection or systemic disease other than nephrotic syndrome. All children in the SSNS group were in remission for at least three months before vaccination. Patients who ever required any immunosuppressive drug therapy other than corticosteroids were excluded from the study. The healthy group consisted of 24 healthy children (17 boys, 7 girls), all of whom were older than 2 years of age, ranging from 4.5 to 14.2 years of age (mean age: 8.55 ± 2.90 years). The children in the healthy group were selected from the general population who had experienced IPD before the study. None of the healthy subjects had a chronic infection or systemic disease. Vaccine All children participating in the study were administered intramuscular 0.5 cc Pneumo23 Ò (Sanofi, Aventis Pasteur; 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F,18C, 19A, 19F, 20, 22F, 23F and 33F) to the deltoid muscle by the same investigator [EU]. Clinical Assessment Parents were advised to observe any local or systemic adverse events including local swelling or erythema, abscess formation, fever, and other signs of a systemic disease. Clinical Exacerbation No relapse was observed in any child in the SSNS group over 6 months of follow-up after vaccination. Side effects No side effects related to the vaccine were observed throughout the study. Immune Response Assessment All subjects underwent blood sampling for IgG antibodies to pneumococcal capsular polysaccharide antigen (PCP) before and 6 weeks after vaccination, and serum samples were stored at -20°C until analysis. Anti-pneumococcal capsular polysaccharide titers (Anti-PCP IgG) levels were measured by ELISA [15,16] using the Anti-PCP IgG kit (enzyme immunoassay Kit, MK012, Binding Site, Ltd, UK) [17] and interpreted as µg/ml. A two-fold or greater increase in antibody titer after vaccination was considered seroconversion and positive vaccine response. Statistical Analysis SPSS 29.0 (IBM Corp, Armonk, NY, USA) was used for all statistical evaluations. The data were analyzed using the Shapiro-Wilk test. Since all continuous data were not normally distributed, non-parametric tests were applied. The Mann-Whitney U test was used to compare the groups. The chi-square test was used to analyze differences in frequencies between categorical data. The Spearman rank correlation test was used to investigate the relationships between continuous variables. A p-value of less than 0.05 was considered as significant. Results Demographic data of the groups The mean age and female: male ratio of the SSNS group were comparable to those of the children in the healthy group (Table 1) Table 1: Demographic data of the Steroid-sensitive nephrotic and healthy groups Steroid-Sensitive Nephrotic Syndrome Group Healthy Group p value Number of cases N( F/M) 30 (10 / 20) 24 (7/17) 0.743 a Age mean± SD (min-max) 8.40±3.51 (2.7- 15.5 years) 8.55±2.9 (4.5-14.1 years) 0.728 b Number of relapses mean± SD (min-max) 1.2 ± 1.3 (0–5 ) ---- ---- Cumulative corticosteroid dose mean± SD (min-max) 4540 ± 2900 (1448-13324 mg) ------ ------ (%95 confidence interval), SD: standard deviation, a : Chi-Square test, b : Man-Whitney U test. The level of antibody (Anti-PCP IgG) titers and the frequency of positive response after vaccination No statistically significant difference was found between males and females regarding positive vaccine response rates (p = 0.079) and the change in anti-PCP IgG titers (p = 0.183). In addition, age was not correlated to anti-PCP IgG titers both at baseline visit before vaccination (n = 54, r = 0.158; p:0.253) and in 6 th week after vaccination (n = 54, r = -0.126, p:0.362). (Table 2) Table 2: Correlation between the vaccine response and the factors affecting PPV23 vaccine response Age (All children) Number of relapses (SSNS group) Cumulative corticosteroid dose (SSNS group) Anti-PCP IgG-I r = 0,158 (p=0,253) a r=0,084 (p=0,658) c r=0.220 (p=0,243) e DeltaAnti-PCP IgG-I levels r=-0,126 (p=0,362) b r=0.044 (p= 0,818) d r=-0,053 (p=0,779) f Data represent the correlation test results: a: correlation between the age and pre-vaccination antibody titers in all children, b: correlation between the age and post-vaccination antibody increase rate in all children, c: correlation between the number of relapses and pre-vaccination antibody titers in the SSNS group. d: correlation between the number of relapses and post-vaccination antibody titers increase rates in the SSNS group, e: correlation between the cumulative corticosteroid doses and pre-vaccination antibody titers in the SSNS group, f: correlation between the cumulative corticosteroid doses and post-vaccination antibody titers increase rates in the SSNS group. At baseline, no statistically significant differences were observed between the SSNS group and the healthy group in terms of the geometric mean of anti-pneumococcal capsular polysaccharide titers ( GM of Anti-PCP IgG) (p=0.205). Similarly, there was no difference in post-vaccination GM of anti-PCP IgG titers between the SSNS group and the healthy group (p= 0.280). Furthermore, the change in antibody titers from baseline to week 6 after vaccination did not differ between the two groups (p= 0.393) (Table 3). Table 3: Geometric mean of antibody concentration to the pneumococcal capsular polysaccharide and Positive vaccine response rates of subjects in the main groups Steroid Sensitive Nephrotic Syndrome Group (n:30) Healthy Group (n:24) p value Pre-Vaccination Ab. titers (GM of Anti-PCP IgG-I) mean±SD (min-max) 31.96±24.10 µg/l (4.00–85.85) 44.35±45.59 µg/l (2.95–168.34) p:0.205 a Post-Vaccination Ab. titers (GM of Anti-PCP IgG-II) mean±SD (min-max) 213.06±96.19 µg/l (55,87–360.54) 247.16±133.04 µg/l (29.39–431.52) p:0.280 b Delta anti-PCP IgG titers (GM of Ab. Increase Rates) 11,14 ±9,21 (1.96-34.56) 14,78 ±20,75 (1.56-95.48) p:0.393 c Positive vaccine response-I (Two-Fold Increase) %93,3 (n:28) %95,8 (n:23) p:0.690 d Positive vaccine response-II (Four-Fold Increase) %56,6 (n:17) %58,3 (n:14) p: 0.902 e Data represent geometric mean antibody concentration (%95 confidence interval), a : b : c : Mann Whitney U test, d : e : Chi-Square. GM: geometric mean, Ab: antibody, Anti-PCP IgG-I: pre-vaccination antibody levels[μg/ml], Anti-PCP IgG-II: post-vaccination antibody levels[μg/ml], Increase Rates: the increase rates of the antibody titers after vaccination with PPV23. Twenty-eight children (93.3%) in the SSNS group(n=30) and 23 children (95.8%) in the healthy group (n=24) showed a positive immune response to the vaccine, as indicated by a two-fold increase in anti-PCP Ig G titers with vaccination. This vaccine response was not statistically different between the two groups (p= 0.609). If the positive immune response is accepted as a four-fold increase in anti-PCP IgG titers, 17 children in the SSNS group and 14 children in the healthy group exhibited a positive immune vaccine response. No statistically significant difference was detected between the two groups in terms of vaccine response (p= 0.769). Effect of corticosteroid dose on vaccine response: The median cumulative corticosteroid dose in the SSNS group was 3500 mg (range 1448-13324 mg). The cumulative corticosteroid dose in the SSNS group was not correlated with the pre-vaccination natural anti-PCP IgG-I titer (r: 0.220, p:0.243) and also with the change in antibody titers after vaccination (r: 0.053; p:0,779). (Table 2) The impact of relapses on vaccine response: Out of the 30 children in the SSNS group, 18 (60.0%) had relapsed before the vaccination. The mean number of relapses was 1.2 ± 1.3 (0–5 )and their distribution was as follows: 7 cases had one relapse, 4 cases had two relapses, 4 cases had three relapses, 2 cases had four relapses, and one case had five relapses. There was no relapse in 12 children in the SSNS group. There was no association between the number of relapses and the pre-vaccination natural-baseline Anti-PCP IgG titer s in the SSNS group (r: 0.084; p:0.658). No association was also found between the number of relapses and the change in antibody titers with vaccination in the SSNS group (r: 0.044; p: 0.818). (Table 2) Discussion This study represents one of the first comprehensive evaluations of the immune response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in children with steroid-sensitive nephrotic syndrome (SSNS), thereby addressing a critical gap in the existing literature on this topic. Prior research has indicated that children with INS elicit antibody responses that are comparable to those observed in healthy controls following vaccination with the 14-valent or lower-valent PPVs, both of which are no longer in use. Although these studies reported high rates of positive vaccine responses in both groups [10,11,12], the use of radioimmunoassay (RIA) as the primary method for measuring antibody titers limited the accuracy of these findings due to the low sensitivity of the method in detecting the pneumococcal antibody responses [16]. Our study, which employed the more reliable enzyme-linked immunosorbent assay (ELISA), provides clear evidence that children with SSNS exhibit a robust immune response to PPV23, with at least a two-fold increase in anti-pneumococcal antibody titers in the majority of the group (Figure 1). The rate of positive immune responses, defined as at least a two-fold increase in antibody titers, was 93.3% (28/30) in the SSNS group and 95.8% (23/24) in the healthy group, with no statistically significant difference between the two groups (p > 0.05). Even when the threshold for a positive response was set to a four-fold increase in antibody titers, the response rates remained comparable between 2 groups with a 56.6% (17/30) immunogenicity in the SSNS group and 58.3% (14/24) in the healthy group. These results highlight that children with SSNS can achieve an adequate immune response to PPV23 despite their acquired immune deficiency status. These results point out an important step in understanding the efficacy of the vaccine among this vulnerable population. In a previous study comparing the antibody response to 23-value PPV in high-risk groups for IPD, the rates of seropositivity were somewhat lower both in the patient group (68.7 %) and in the healthy group (66.0 %) [18]. In contrast, we demonstrated higher rates of antibody response both in children with INS and in healthy children. On the other hand, our results are consistent with the studies of Güven et al. [19], and Ulinski et al. [20], in which only children with INS were included, and all subjects developed an adequate response to the 23-valent PPV. All cases included in our study were more than 2 years of age because pneumococcal polysaccharide vaccines (PPVs) are licensed for administration to these children. The antigenic effects of pneumococcal polysaccharides are T-cell independent. They have limited immunogenicity for major pneumococcal serotypes during infancy [21]. In addition, there is limited data on the association of immunogenicity of PPVs with increasing age. We found no correlation between age and the deltaPCP-IgG titers after the vaccination (n=54, r=0.126). The antibody responses to the 23-valent pneumococcal vaccine in children were age-independent. In our study, pre-vaccination GM of anti-PCP IgG titers in both groups were similar. Similarly, no statistically significant difference was found between the GM of anti-PCP IgG levels after 23-valent PPV in the INS and healthy groups (p > 0.05). Our results showed that the positive response to the 23-valent PPV vaccine in the SSNS group was almost similar to that in healthy children (Figure 1). Our high positive antibody response rates with vaccination may be related to the fact that we vaccinated them while they were in remission. In contrast, it is known that the immunologic problems in INS may be exacerbated during active disease and treatment periods with immunosuppressive drugs. Although it was thought that administering vaccines during a relapse or while receiving corticosteroid therapy would adversely affect vaccine responses in children with SSNS, it has been reported that the immune response to 13-valued PPV was not affected by the stage of the INS in children [11]. Also, Wilkes reported that corticosteroid treatment did not affect the immune response to 14-valent PPV in children with INS [22]. Subsequent studies showed that although children with INS had adequate antibody responses to the 14- or lower-valent PPVs, post-vaccination anti-pneumococcal antibody titers in children with INS were lower than those in healthy children [12,23]and in healthy adults [24]. Moreover, a study showed that children with INS who were in remission had a positive antibody response to the Hepatitis B vaccine. Still, the response rate in active disease and during corticosteroid therapy was very low compared to healthy children [25]. On the contrary, Güven et al . [19] and Ulinski et al . [20] demonstrated a very high immune response to the 23-valent vaccine in children with INS even during active disease. In our study, the similar pre-vaccination natural pneumococcal antibody levels in children with INS and the healthy group suggest that antibody-related immune functions are largely restored during the recovery phase of the disease. These positive antibody responses were not associated with cumulative corticosteroid dose and relapse rates. Contrary to this finding, pre -vaccination anti-PCP antibody levels to the 23-valent PPV were considerably lower in 3 high-risk patient groups for IPD, including NS and asthmatic and splenectomized children [18]. The colonization and previous pneumococcal infections in healthy individuals cause a certain level of IgG-type antibodies in serum [26]. In children with INS, pre-vaccination natural anti-pneumococcal antibody levels are expected to be low due to the loss of immunoglobulins in urine during relapses and immunosuppressive effects of corticosteroid usage in treatment. Children with NS may lose the ability to develop an immune response during the active phase of the disease. Kemper reported that IgG-1–3 against pneumococcal antigen decreased during relapse in NS in children and increased after relapse. However, it was shown that the course of this increase was also variable among IgG subtypes [27]. Heslan et al. reported that decreased IgG production and serum Ig G levels in INS children were reversible after remission [28]. Our study is limited by the lack of long-term follow-up and the global IgG measurement with ELISA, which lacks serotype-specific testing [15,16]. Although a good correlation has been demonstrated between anti-pneumococcal antibodies measured by the global ELISA test and those measured by the serotype-specific test [29], WHO recommends serotype-specific testing as the gold standard in the evaluation of response to new pneumococcal conjugate vaccines [26,29,30,31]. In conclusion, the 23-valent pneumococcal polysaccharide vaccine (PPV23) can be safely administered to children with steroid-sensitive nephrotic syndrome (SSNS) without any associated adverse effects. The 23-valent pneumococcal polysaccharide vaccine is safe and elicits a robust immune response in children with idiopathic nephrotic syndrome similar to healthy children. The number of disease relapses and the cumulative prednisolone dose does not appear to exert any influence either on the pre-vaccination or on the post-vaccination antibody levels in patients with steroid-sensitive nephrotic syndrome (SSNS). Nevertheless, the longevity of the protective antibody response remains unclear and requires further investigation. Declarations Contributions Conceptualization/design and methodology: SÇ. Data acquisition: EU and SÇ. Data analysis and interpretation: EU, SÇ. Manuscript preparation: All authors. Study accountability: EU. All authors approved the final manuscript and accepted full responsibility for the work. Competing Interests and Funding Competing interests The authors declare that they have no competing interests. Funding Istanbul University Scientific Research Projects supported the study (grant No: T-626) Ethics approval and consent to participate Consent statement Written consent was obtained from all subjects. Ethics declarations This study followed the ethical principles of the Declaration of Helsinki. The Ethics Committee of the Istanbul University-Cerrahpaşa (formerly Istanbul University) approved the study (approval No. 3248). Acknowledgments The authors would like to thank the patients and parents who voluntarily participated in this study. This research has been presented as an oral presentation at the 11 th Europaediatrics Congress in 2024 (https://doi.org/10.1136/bmjpo-2024-EPAC.51) References Noone DG, Iijima K, Parekh R (2018). Idiopathic nephrotic syndrome in children. The Lancet, 392, 61–74. https://doi.org/10.1016/S0140-6736(18)30536-1 Kaneko K, Tsuji S, Kimata T, Kitao T, Yamanouchi S, Kato S (2015). 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IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with The Binding Site reagents. Clinical Chemistry, 49(11), 1924–1929. https://doi.org/10.1373/clinchem.2003.022350 Siber GR, Chang I, Baker S, Fernsten P, O'Brien KL, Santosham M, Reid GR, Thompson C, Madore D, Kohberger R, Hackell J, Paradiso PR (2007). Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine, 25(19), 3816–3826. https://doi.org/10.1016/j.vaccine.2007.01.119 Cite Share Download PDF Status: Published Journal Publication published 19 Nov, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Major Revisions Needed 28 Jul, 2025 Reviewers agreed at journal 21 Jun, 2025 Reviewers invited by journal 20 Jun, 2025 Editor assigned by journal 20 Jun, 2025 First submitted to journal 19 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6933268","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":474129308,"identity":"204d9179-5030-441e-b09b-5210a429b584","order_by":0,"name":"Ersin Ulu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArUlEQVRIiWNgGAWjYDCCA0D8gMGGgUGCJC0JDGmkazlMgha+24ePSSS2nU/sn9188AFDjU00QS2S59LSgFpuJ864cyzZgOFYWm4DIS0GZ3jMwFoabuSYSTA2HCZGC/83oJZzifNJ0MLDBtRyIHED0Vokz7AZWyScSzbeeCMt2SCBGL/wnWF+eONDmZ3svBvJBx98qLEhrAUGHMEqE4hVDgL2pCgeBaNgFIyCEQYAA8VDLVmd02sAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-9798-2367","institution":"Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine: Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi","correspondingAuthor":true,"prefix":"","firstName":"Ersin","middleName":"","lastName":"Ulu","suffix":""},{"id":474129309,"identity":"46fe5797-8027-4519-a221-07ce1990836f","order_by":1,"name":"Salim Calışkan","email":"","orcid":"","institution":"Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine: Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Salim","middleName":"","lastName":"Calışkan","suffix":""}],"badges":[],"createdAt":"2025-06-19 17:23:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6933268/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6933268/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-07026-3","type":"published","date":"2025-11-19T15:57:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85305608,"identity":"8e6e4ebd-91df-4185-952c-2feeacbbadbe","added_by":"auto","created_at":"2025-06-24 12:40:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":46291,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePPV23 antibody (\u003c/strong\u003eAnti-PCP IgG)\u003cstrong\u003e titers before and after vaccination and change rates in antibody titers after vaccination (delta \u003c/strong\u003eAnti-PCP IgG\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSSNS: Steroid-sensitive nephrotic syndrome. Anti-PCP IgG-I: pre-vaccination antibody levels[μg/ml], Anti-PCP IgG-II: post-vaccination antibody levels[μg/ml], delta anti-PCP IgG titers: post-vaccination antibody titers increase rates.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6933268/v1/1b6c43abd6d99d8a0fb28265.png"},{"id":96649992,"identity":"b6845543-b7bb-42e2-908c-080994697132","added_by":"auto","created_at":"2025-11-24 16:03:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1048498,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6933268/v1/97e468fc-1734-4058-99e1-749ecd030c39.pdf"}],"financialInterests":"","formattedTitle":"Immunogenicity of the 23-Valent Polysaccharide Pneumococcal Vaccine in Children with Idiopathic Nephrotic Syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIdiopathic nephrotic syndrome (INS) is the most common chronic kidney disease in pediatric populations. Immune dysregulation plays a significant role in its pathophysiology. Thanks to the effective use of antibiotics and corticosteroids, the mortality rate of children with nephrotic syndrome (NS) has decreased to less than 5% in recent years. The most common subtype of INS in childhood, known as steroid-responsive/sensitive nephrotic syndrome (SSNS), responds well to corticosteroid treatment. However, SSNS is a recurrent disease in a significant number of patients, with two-thirds of cases relapsing after initial treatment. Recurrent relapses are associated with higher morbidity. Infections, particularly invasive pneumococcal disease (IPD), could play a role in triggering the relapse [1]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn acquired immune deficiency in INS predisposes individuals to IPD. Many factors have been demonstrated to exert a deleterious effect on the immune system in INS, and these may be present concurrently at different stages of the disease. Previously, it was thought that T cell-dependent immune dysregulation was the primary cause of the disease. Recent evidence indicates that podocyte-related disorders and even B-cell disorders may also play a significant role [2,3]. A notable depletion of immunoglobulins in the urine is observed during the initial stages of the disease and the recurring relapses [4]. Corticosteroid usage in the treatment may also contribute to the immunosuppression related to disease per se.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs a result, the decreased immunoglobulin levels, widespread protein deficiency, impaired opsonization, and reduced spleen function observed in NS patients make them susceptible to infections. Additionally, components of the alternative complement pathway, such as factors B and D, are lost in the urine. This loss causes a lack of opsonization of encapsulated microorganisms, including Pneumococci and \u003cem\u003eEscherichia coli\u003c/em\u003e. Peritonitis, cellulitis, and sepsis caused by encapsulated microorganisms, particularly Pneumococci, are more common in these patients [5,6,7].\u003c/p\u003e\n\u003cp\u003eChildren with INS are at an elevated risk for developing invasive pneumococcal disease (IPD). Vaccinating INS patients with the polysaccharide pneumococcal vaccine has been recommended for several years to protect them from IPD [8,9]. However, the acquired immunodeficiency in INS has elicited concerns on the immunogenicity of the patients to this vaccine. Consequently, antibody responses to pneumococcal vaccines have been investigated in children with INS [10]. Previously, antibody responses to 14-valent and lower-valent PPV in children with INS were as satisfactory as it was in the healthy control group[11,12].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFollowing the extensive implementation of the 14-valent vaccine, epidemiological investigations in the general population have demonstrated a reduction in the incidence of IPD attributable to the serotypes included in this vaccine. In contrast, the number of IPD associated with the serotypes not included in this vaccine has increased over time. \u0026nbsp; Nevertheless, the number of serotypes responsible for IPD has increased over time, reaching over 100 capsular serotypes of Streptococcus Pneumoniae [13,14]. A novel PPV vaccine comprising 23 pneumococcal serotypes, the most prevalent cause of IPD, was introduced in 1983. However, polysaccharide pneumococcal vaccines (PPV) were only capable of eliciting an immune response after the age of two. Although conjugate pneumococcal vaccines are effective in children under 2 years of age, they contain fewer serotypes than the 23-valent PPV.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSince the conjugate vaccines administered during infancy provide partial protection, the current guidelines recommend at least one dose of \u0026nbsp; PPV23 after 2 years of age for high-risk groups. The objective of this study is to evaluate the immunogenicity of PPV23 in children with SSNS in comparison to healthy controls. Furthermore, the study aims to investigate the influence of the frequency of disease relapse and cumulative corticosteroid doses on antibody levels at the baseline and the 6\u003csup\u003eth\u0026nbsp;\u003c/sup\u003eweek of vaccination in children with SSNS.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Design and Subjects\u003c/em\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the local ethics committee of Istanbul University-Cerrahpaşa (formerly Istanbul University), Cerrahpaşa Faculty of Medicine (No: 3248). Only those who provided informed consent were included in the study. Individuals with a history of hypersensitivity to any vaccine were excluded. None of the participants had received any pneumococcal vaccine before the study.\u003c/p\u003e\n\u003cp\u003ePatients with a diagnosis of minimal change nephrotic syndrome who were regularly followed up in the department of pediatric nephrology and who were responsive to corticosteroid therapy were enrolled in the study. A total of 30 children, comprising 10 boys and 20 girls, were included in the SSNS group. The subjects were all older than two years of age, ranging from 2.7 years to 15.5 years (mean age: 8.40 ± 3.51 years). No patients had any chronic infection or systemic disease other than nephrotic syndrome. All children in the SSNS group were in remission for at least three months before vaccination. Patients who ever required any immunosuppressive drug therapy other than corticosteroids were excluded from the study.\u003c/p\u003e\n\u003cp\u003eThe healthy group consisted of 24 healthy children (17 boys, 7 girls), all of whom were older than 2 years of age, ranging from 4.5 to 14.2 years of age (mean age: 8.55 ± 2.90 years). The children in the healthy group were selected from the general population who had experienced IPD before the study. None of the healthy subjects had a chronic infection or systemic disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eVaccine\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll children participating in the study were administered intramuscular 0.5 cc Pneumo23\u003csup\u003eÒ\u003c/sup\u003e (Sanofi, Aventis Pasteur; 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F,18C, 19A, 19F, 20, 22F, 23F and 33F) to the deltoid muscle by the same investigator [EU].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical Assessment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParents were advised to observe any local or systemic adverse events including local swelling or erythema, abscess formation, fever, and other signs of a systemic disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical Exacerbation\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo relapse was observed in any child in the SSNS group over 6 months of follow-up after vaccination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSide effects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo side effects related to the vaccine were observed throughout the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eImmune Response Assessment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll subjects underwent blood sampling for IgG antibodies to pneumococcal capsular polysaccharide antigen (PCP) before and 6 weeks after vaccination, and serum samples were stored at -20°C until analysis. Anti-pneumococcal capsular polysaccharide titers (Anti-PCP IgG) levels were measured by ELISA [15,16] using the Anti-PCP IgG kit (enzyme immunoassay Kit, MK012, Binding Site, Ltd, UK) [17] \u0026nbsp;and interpreted as µg/ml. A two-fold or greater increase in antibody titer after vaccination was considered seroconversion and positive vaccine response.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS 29.0 (IBM Corp, Armonk, NY, USA) was used for all statistical evaluations. The data were analyzed using the Shapiro-Wilk test. Since all continuous data were not normally distributed, non-parametric tests were applied. The Mann-Whitney U test was used to compare the groups. The chi-square test was used to analyze differences in frequencies between categorical data. The Spearman rank correlation test was used to investigate the relationships between continuous variables. A p-value of less than 0.05 was considered as significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDemographic data of the groups\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean age and female: male ratio of the SSNS group were comparable to those of the children in the healthy group (Table 1)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Demographic data of the Steroid-sensitive nephrotic and healthy groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSteroid-Sensitive Nephrotic Syndrome Group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy Group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of cases\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN( F/M)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e30 (10 / 20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e24 (7/17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.743\u003cstrong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003emean\u0026plusmn; SD\u003c/p\u003e\n \u003cp\u003e(min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e8.40\u0026plusmn;3.51\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(2.7- 15.5 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e8.55\u0026plusmn;2.9\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(4.5-14.1 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e0.728\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of relapses\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003emean\u0026plusmn; SD\u003c/p\u003e\n \u003cp\u003e(min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e1.2 \u0026plusmn; 1.3\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0\u0026ndash;5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e----\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e----\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative corticosteroid dose\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003emean\u0026plusmn; SD\u003c/p\u003e\n \u003cp\u003e(min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e4540 \u0026plusmn; 2900\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(1448-13324 mg)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e------\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e------\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e(%95 confidence interval), SD: standard deviation, \u003csup\u003ea\u003c/sup\u003e:\u003csup\u003e\u0026nbsp;\u003c/sup\u003eChi-Square test, \u003csup\u003eb\u003c/sup\u003e: Man-Whitney U test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eThe level of antibody\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;(Anti-PCP IgG) titers and\u0026nbsp;\u003c/em\u003e\u003cem\u003ethe frequency of positive response after vaccination\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo statistically significant difference was found between males and females regarding positive vaccine response rates (p = 0.079) and the change in anti-PCP IgG titers (p = 0.183). \u0026nbsp;In addition, age was not correlated to anti-PCP IgG titers both at baseline visit before vaccination (n = 54, r = 0.158; p:0.253) and in 6\u003csup\u003eth\u0026nbsp;\u003c/sup\u003eweek after vaccination (n = 54, r = -0.126, p:0.362). (Table 2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Correlation between the vaccine response and the factors affecting PPV23 vaccine response\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (All children)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of relapses (SSNS group)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative corticosteroid dose (SSNS group)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eAnti-PCP IgG-I\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003er = 0,158 (p=0,253)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003er=0,084 (p=0,658)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003er=0.220 (p=0,243)\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eDeltaAnti-PCP IgG-I levels\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003er=-0,126 (p=0,362)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003er=0.044 (p= 0,818)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003er=-0,053 (p=0,779)\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eData represent the correlation test results: a:\u003c/em\u003e correlation between the age and \u003cem\u003epre-vaccination antibody titers in all children, b:\u0026nbsp;\u003c/em\u003ecorrelation between the age and \u003cem\u003epost-vaccination antibody increase rate in all children, c:\u003c/em\u003e correlation between the number of relapses and \u003cem\u003epre-vaccination antibody titers in the SSNS group. d:\u0026nbsp;\u003c/em\u003ecorrelation between the number of relapses and \u003cem\u003epost-vaccination antibody titers increase rates in the SSNS group, e:\u003c/em\u003e correlation between the cumulative corticosteroid doses and \u003cem\u003epre-vaccination antibody titers in the SSNS group, f:\u0026nbsp;\u003c/em\u003ecorrelation between the cumulative corticosteroid doses and \u003cem\u003epost-vaccination antibody titers increase rates in the SSNS group.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt baseline, no statistically significant differences were observed between the SSNS group and the healthy group in terms of the geometric mean of anti-pneumococcal capsular polysaccharide titers (\u003cstrong\u003eGM of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eAnti-PCP IgG)\u003c/em\u003e\u003c/strong\u003e (p=0.205). Similarly, there was no difference in post-vaccination GM of anti-PCP IgG titers between the SSNS group and the healthy group (p= 0.280). Furthermore, the change in antibody titers from baseline to week 6 after vaccination did not differ between the two groups (p= 0.393) (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 3: Geometric mean of antibody concentration to the pneumococcal capsular polysaccharide and Positive vaccine response rates of subjects in the main groups\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 162px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSteroid Sensitive Nephrotic Syndrome Group (n:30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy Group (n:24)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;p value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-Vaccination Ab. titers\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(GM of Anti-PCP IgG-I)\u003c/p\u003e\n \u003cp\u003emean\u0026plusmn;SD\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31.96\u0026plusmn;24.10 \u0026micro;g/l\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(4.00\u0026ndash;85.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003e44.35\u0026plusmn;45.59 \u0026micro;g/l\u003c/p\u003e\n \u003cp\u003e(2.95\u0026ndash;168.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003ep:0.205\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-Vaccination Ab. titers\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(GM of Anti-PCP IgG-II)\u003c/p\u003e\n \u003cp\u003emean\u0026plusmn;SD\u003c/p\u003e\n \u003cp\u003e(min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e213.06\u0026plusmn;96.19 \u0026micro;g/l\u003c/p\u003e\n \u003cp\u003e(55,87\u0026ndash;360.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003e247.16\u0026plusmn;133.04 \u0026micro;g/l\u003c/p\u003e\n \u003cp\u003e(29.39\u0026ndash;431.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003ep:0.280\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelta anti-PCP IgG titers\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(GM of \u0026nbsp;Ab. Increase Rates)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11,14 \u0026plusmn;9,21\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(1.96-34.56)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003e14,78 \u0026plusmn;20,75\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(1.56-95.48)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003ep:0.393\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive vaccine response-I\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(Two-Fold Increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e%93,3\u003c/p\u003e\n \u003cp\u003e(n:28) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003e\u0026nbsp;%95,8\u003c/p\u003e\n \u003cp\u003e(n:23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003ep:0.690\u003csup\u003e\u0026nbsp;d\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive vaccine response-II\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(Four-Fold Increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026nbsp;%56,6\u003c/p\u003e\n \u003cp\u003e(n:17)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003e\u0026nbsp;%58,3\u003c/p\u003e\n \u003cp\u003e(n:14)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003ep: 0.902\u003csup\u003e\u0026nbsp;e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData represent geometric mean antibody concentration (%95 confidence interval), \u003csup\u003ea\u003c/sup\u003e: \u003csup\u003eb\u003c/sup\u003e: \u003csup\u003ec\u003c/sup\u003e: Mann Whitney U test, \u003csup\u003ed\u003c/sup\u003e: \u003csup\u003ee\u003c/sup\u003e: Chi-Square. GM: geometric mean, Ab: antibody, Anti-PCP IgG-I: pre-vaccination antibody levels[\u0026mu;g/ml], Anti-PCP IgG-II: post-vaccination antibody levels[\u0026mu;g/ml], Increase Rates: the increase rates of the antibody titers after vaccination with PPV23.\u003c/p\u003e\n\u003cp\u003eTwenty-eight children (93.3%) in the SSNS group(n=30) and 23 children (95.8%) in the healthy group (n=24) showed a positive immune response to the vaccine, as indicated by a two-fold increase in \u003cem\u003eanti-PCP Ig G\u003c/em\u003e titers with vaccination. This vaccine response was not statistically different between the two groups (p= 0.609). If the positive immune response is accepted as a four-fold increase in \u003cem\u003eanti-PCP IgG\u003c/em\u003e titers, 17 children in the SSNS group and 14 children in the healthy group exhibited a positive immune vaccine response. No statistically significant difference was detected between the two groups in terms of vaccine response (p= 0.769).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEffect of corticosteroid dose on vaccine response:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median cumulative corticosteroid dose in the SSNS group was 3500 mg (range 1448-13324 mg).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe cumulative corticosteroid dose in the SSNS group was not correlated with the pre-vaccination natural \u003cem\u003eanti-PCP IgG-I\u003c/em\u003e titer (r: 0.220, p:0.243) and also with the change in antibody titers after vaccination (r: 0.053; p:0,779). (Table 2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eThe impact of relapses on vaccine response:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of the 30 children in the SSNS group, 18 (60.0%) had relapsed before the vaccination. The mean number of relapses was 1.2 \u0026plusmn; 1.3 (0\u0026ndash;5 )and their distribution was as follows: 7 cases had one relapse, 4 cases had two relapses, 4 cases had three relapses, 2 cases had four relapses, and one case had five relapses. There was no relapse in 12 children in the SSNS group.\u003c/p\u003e\n\u003cp\u003eThere was no association between the number of relapses and the pre-vaccination natural-baseline \u003cem\u003eAnti-PCP IgG titer\u003c/em\u003es in the SSNS group (r: 0.084; p:0.658). No association was also found between the number of relapses and the change in antibody titers with vaccination in the SSNS group (r: 0.044; p: 0.818). (Table 2)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study represents one of the first comprehensive evaluations of the immune response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in children with steroid-sensitive nephrotic syndrome (SSNS), thereby addressing a critical gap in the existing literature on this topic. Prior research has indicated that children with INS elicit antibody responses that are comparable to those observed in healthy controls following vaccination with the 14-valent or lower-valent PPVs, both of which are no longer in use. Although these studies reported high rates of positive vaccine responses in both groups [10,11,12], the use of radioimmunoassay (RIA) as the primary method for measuring antibody titers limited the accuracy of these findings due to the low sensitivity of the method in detecting the pneumococcal antibody responses [16]. Our study, which employed the more reliable enzyme-linked immunosorbent assay (ELISA), provides clear evidence that children with SSNS exhibit a robust immune response to PPV23, with at least a two-fold increase in anti-pneumococcal antibody titers in the majority of the group (Figure 1).\u003c/p\u003e\n\u003cp\u003eThe rate of positive immune responses, defined as at least a two-fold increase in antibody titers, was 93.3% (28/30) in the SSNS group and 95.8% (23/24) in the healthy group, with no statistically significant difference between the two groups (p \u0026gt; 0.05). Even when the threshold for a positive response was set to a four-fold increase in antibody titers, the response rates remained comparable between 2 groups with a 56.6% (17/30) immunogenicity in the SSNS group and 58.3% (14/24) in the healthy group. These results highlight that children with SSNS can achieve an adequate immune response to PPV23 despite their acquired immune deficiency status. These results point out an important step in understanding the efficacy of the vaccine among this vulnerable population.\u003c/p\u003e\n\u003cp\u003eIn a previous study comparing the antibody response to 23-value PPV in high-risk groups for IPD, the rates of seropositivity were somewhat lower both in the patient group (68.7 %) and in the healthy group (66.0 %) [18]. In contrast, we demonstrated higher rates of antibody response both in children with INS and in healthy children. On the other hand, our results are consistent with the studies of Güven et al. [19], and Ulinski et al. [20], in which only children with INS were included, and all subjects developed an adequate response to the 23-valent PPV.\u003c/p\u003e\n\u003cp\u003eAll cases included in our study were more than 2 years of age because pneumococcal polysaccharide vaccines (PPVs) are licensed for administration to these children. The antigenic effects of pneumococcal polysaccharides are T-cell independent. They have limited immunogenicity for major pneumococcal serotypes during infancy [21]. In addition, there is limited data on the association of immunogenicity of PPVs with increasing age. We found no correlation between age and the deltaPCP-IgG titers\u0026nbsp;after the vaccination (n=54, r=0.126). \u0026nbsp;The antibody responses to the 23-valent pneumococcal vaccine in children were age-independent.\u003c/p\u003e\n\u003cp\u003eIn our study, pre-vaccination GM of anti-PCP IgG titers in both groups were similar. Similarly, no statistically significant difference was found between the GM of anti-PCP IgG levels after 23-valent PPV in the INS and healthy groups (p \u0026gt; 0.05). \u0026nbsp;Our results showed that the positive response to the 23-valent PPV vaccine in the\u0026nbsp;SSNS group was almost similar to that in healthy children (Figure 1). Our high positive antibody response rates with vaccination may be related to the fact that we vaccinated them while they were in remission.\u0026nbsp;In contrast,\u0026nbsp;it is known that the immunologic problems in INS may be exacerbated during active disease and treatment periods with immunosuppressive drugs. Although it was thought that administering vaccines during a relapse or while receiving corticosteroid therapy would adversely affect vaccine responses in children with SSNS, it has been reported that the immune response to 13-valued PPV was not affected by the stage of the INS in children [11]. Also, Wilkes reported that corticosteroid treatment did not affect the immune response to 14-valent PPV in children with INS [22]. Subsequent studies showed that although children with INS had adequate antibody responses to the 14- or lower-valent PPVs, post-vaccination anti-pneumococcal antibody titers in children with INS were lower than those in healthy children [12,23]and in healthy adults [24]. Moreover, a study showed that children with INS who were in remission had a positive antibody response to the Hepatitis B vaccine. Still, the response rate in active disease and during corticosteroid therapy was very low compared to healthy children [25]. On the contrary, Güven \u003cem\u003eet al\u003c/em\u003e. [19] and Ulinski \u003cem\u003eet al\u003c/em\u003e. [20] demonstrated a very high immune response to the 23-valent vaccine in children with INS even during active disease.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, the similar pre-vaccination natural pneumococcal antibody levels in children with INS and the healthy group suggest that antibody-related immune functions are largely restored during the recovery phase of the disease. These positive antibody responses were not associated with cumulative corticosteroid dose and relapse rates. Contrary to this finding, \u003cstrong\u003epre\u003c/strong\u003e-vaccination anti-PCP antibody levels to the 23-valent PPV were considerably lower in 3 high-risk patient groups for IPD, including NS and asthmatic and splenectomized children [18]. The colonization and previous pneumococcal infections in healthy individuals cause a certain level of IgG-type antibodies in serum [26]. In children with INS, pre-vaccination natural anti-pneumococcal antibody levels are expected to be low due to the loss of immunoglobulins in urine during relapses and immunosuppressive effects of corticosteroid usage in treatment. Children with NS may lose the ability to develop an immune response during the active phase of the disease. Kemper reported that IgG-1–3 against pneumococcal antigen decreased during relapse in NS in children and increased after relapse. However, it was shown that the course of this increase was also variable among IgG subtypes [27]. Heslan et al. reported that decreased IgG production and serum Ig G levels in INS children were reversible after remission [28].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study is limited by the lack of long-term follow-up and the global IgG measurement with ELISA, which lacks serotype-specific testing [15,16]. \u0026nbsp;Although a good correlation has been demonstrated between anti-pneumococcal antibodies measured by the global ELISA test and those measured by the serotype-specific test [29], WHO recommends serotype-specific testing as the gold standard in the evaluation of response to new pneumococcal conjugate vaccines [26,29,30,31].\u003c/p\u003e\n\u003cp\u003eIn conclusion, the 23-valent pneumococcal polysaccharide vaccine (PPV23) can be safely administered to children with steroid-sensitive nephrotic syndrome (SSNS) without any associated adverse effects. The 23-valent pneumococcal polysaccharide vaccine is safe and elicits a robust immune response in children with idiopathic nephrotic syndrome similar to healthy children. The number of disease relapses and the cumulative prednisolone dose does not appear to exert any influence either on the pre-vaccination or on the post-vaccination antibody levels in patients with steroid-sensitive nephrotic syndrome (SSNS). Nevertheless, the longevity of the protective antibody response remains unclear and requires further investigation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eContributions\u0026nbsp;\u003c/strong\u003eConceptualization/design and methodology: S\u0026Ccedil;. Data acquisition: EU and S\u0026Ccedil;. Data analysis and interpretation: EU, S\u0026Ccedil;. Manuscript preparation: All authors. Study accountability: EU. All authors approved the final manuscript and accepted full responsibility for the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests and Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIstanbul University Scientific Research Projects supported\u0026nbsp;the study (grant No: T-626)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent was obtained from all subjects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study followed the ethical principles of the Declaration of Helsinki. The Ethics Committee of the Istanbul University-Cerrahpaşa (formerly Istanbul University) \u0026nbsp;approved the study (approval No. 3248).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e The authors would like to thank the patients and parents who voluntarily participated in this study. This research has been presented as an oral presentation at the 11\u003csup\u003eth\u003c/sup\u003e Europaediatrics Congress in 2024 (https://doi.org/10.1136/bmjpo-2024-EPAC.51)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNoone DG, Iijima K, Parekh R (2018). Idiopathic nephrotic syndrome in children. The Lancet, 392, 61\u0026ndash;74. https://doi.org/10.1016/S0140-6736(18)30536-1\u003c/li\u003e\n\u003cli\u003eKaneko K, Tsuji S, Kimata T, Kitao T, Yamanouchi S, Kato S (2015). Pathogenesis of childhood idiopathic nephrotic syndrome: a paradigm shift from T-cells to podocytes. World Journal of Pediatrics, 11(1), 21\u0026ndash;28. https://doi.org/10.1007/s12519-015-0003-9\u003c/li\u003e\n\u003cli\u003eChen J, Qiao XH, Mao JH (2021). Immunopathogenesis of idiopathic nephrotic syndrome in children: two sides of the coin. World Journal of Pediatrics, 17, 115\u0026ndash;122. https://doi.org/10.1007/s12519-020-00400-1\u003c/li\u003e\n\u003cli\u003eHan JW, Lee KY, Hwang JY, Koh DK, Lee JS (2010). Antibody status in children with steroid-sensitive nephrotic syndrome. Yonsei Medical Journal, 51(2), 239\u0026ndash;243. https://doi.org/10.3349/ymj.2010.51.2.239\u003c/li\u003e\n\u003cli\u003eCameron JS (1987). The nephrotic syndrome and its complications. American Journal of Kidney Diseases, 10(3), 157\u0026ndash;171. https://doi.org/10.1016/S0272-6386(87)80170-1\u003c/li\u003e\n\u003cli\u003eGorensek MJ, Lebel MH, Nelson JD (1988). Peritonitis in children with nephrotic syndrome. Pediatrics, 81(6), 849\u0026ndash;856.\u003c/li\u003e\n\u003cli\u003eWu HM, Tang JL, Cao L, Sha ZH, Li Y (2012). Interventions for preventing infection in nephrotic syndrome. Cochrane Database of Systematic Reviews, Issue 4, CD003964. https://doi.org/10.1002/14651858.CD003964.pub3\u003c/li\u003e\n\u003cli\u003eGrabenstein JD, Klugman KP (2012). A century of pneumococcal vaccination research in humans. Clinical Microbiology and Infection, 18(Suppl 5), 15\u0026ndash;24. https://doi.org/10.1111/j.1469-0691.2012.03943.x\u003c/li\u003e\n\u003cli\u003eOrange JS, Ballow M, Stiehm ER, Ballas ZK, Chinen J, De La Morena M, Hossny EM, Lederman HM, Levy J, Shearer WT (2012). Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma \u0026amp; Immunology. Journal of Allergy and Clinical Immunology, 130(3 Suppl), S1\u0026ndash;S24. https://doi.org/10.1016/j.jaci.2012.07.002\u003c/li\u003e\n\u003cli\u003eGoonewardene ST, Tang C, Tan LT-H, Chan K-G, Lingham P, Lee L-H, Goh B-H, Pusparajah P (2019). Safety and efficacy of pneumococcal vaccination in pediatric nephrotic syndrome. Frontiers in Pediatrics, 7, 339. https://doi.org/10.3389/fped.2019.00339\u003c/li\u003e\n\u003cli\u003eFikrig SM, Schiffman G, Phillipp JC, Moel DI (1978). Antibody response to capsular polysaccharide vaccine of Streptococcus pneumoniae in patients with nephrotic syndrome. Journal of Infectious Diseases, 137(6), 818\u0026ndash;821. https://doi.org/10.1093/infdis/137.6.818\u003c/li\u003e\n\u003cli\u003eSpika JS, Halsey NA, Schiffman G, Wald ER, McCracken GH Jr, Nelson JD (1986). Decline of vaccine-induced antipneumococcal antibody in children with nephrotic syndrome. American Journal of Kidney Diseases, 7(6), 466\u0026ndash;470. https://doi.org/10.1016/S0272-6386(86)80186-X\u003c/li\u003e\n\u003cli\u003eButler JC, Hofmann J, Cetron MS, Elliott JA, Facklam RR, Breiman RF (2004). Epidemiology of pneumococcal disease. In: Tuomanen E, Mitchell T, Morrison D, Spratt B, editors. The pneumococcus. 1st ed. Washington, DC: American Society for Microbiology, pp. 148\u0026ndash;168. https://doi.org/10.1128/9781555816537.ch10\u003c/li\u003e\n\u003cli\u003eLadhani SN, Collins S, Djennad A, Sheppard CL, Borrow R, Fry NK, Andrews NJ, Ramsay ME (2018). Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000\u0026ndash;17: a prospective national observational cohort study. The Lancet Infectious Diseases, 18(4), 441\u0026ndash;451. https://doi.org/10.1016/S1473-3099(18)30052-5\u003c/li\u003e\n\u003cli\u003eMusher DM, Luchi MJ, Watson DA, Hamilton R, Baughn RE (1990). Pneumococcal polysaccharide vaccine in young adults and older bronchitics: determination of IgG responses by ELISA and the effect of adsorption of serum with non-type-specific cell wall polysaccharide. Journal of Infectious Diseases, 161(4), 728\u0026ndash;735. https://doi.org/10.1093/infdis/161.4.728\u003c/li\u003e\n\u003cli\u003eWernette CM, Frasch CE, Madore D, Carlone G, Goldblatt D, Plikaytis B, Benjamin WH, Quataert SA, Hildreth S, Sikkema DJ, K\u0026auml;yhty H, Jonsdottir I, Nahm MH (2003). Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clinical and Diagnostic Laboratory Immunology, 10(4), 514\u0026ndash;519. https://doi.org/10.1128/cdli.10.4.514-519.2003\u003c/li\u003e\n\u003cli\u003eThe Binding Site Group Ltd (2014). VaccZyme\u0026trade; Anti-PCP IgG Enzyme Immunoassay Kit for in-vitro diagnostic use (Product code: MK012). Birmingham, UK: The Binding Site Group Ltd, pp. 12\u0026ndash;14. Accessed 17 January 2025.\u003c/li\u003e\n\u003cli\u003eLee HJ, Kang JH, Kim KH, Kim DS, Kim KN, Kim YJ, Kim YK, Kim YT, Namgoong JM, Rhee DK, Shin SM, Song JY, Yoon YK, Yu J, Lee H (1995). Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in healthy children and in children at increased risk of pneumococcal infection. Vaccine, 13(16), 1533\u0026ndash;1538. https://doi.org/10.1016/0264-410X(95)00093-G\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;ven AG, Akman S, Bahat E, Senyurt M, Y\u0026uuml;zbey S, Uguz A, Yegin O (2004). Rapid decline of anti-pneumococcal antibody levels in nephrotic children. Pediatric Nephrology, 19, 61\u0026ndash;65. https://doi.org/10.1007/s00467-003-1331-x\u003c/li\u003e\n\u003cli\u003eUlinski T, Leroy S, Dubrel M, Danon S, Bensman A (2008). High serological response to pneumococcal vaccine in nephrotic children at disease onset on high-dose prednisone. Pediatric Nephrology, 23, 1107\u0026ndash;1113. https://doi.org/10.1007/s00467-008-0782-5\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Brien KL, Hochman M, Goldblatt D (2007). Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue? The Lancet Infectious Diseases, 7(9), 597\u0026ndash;606. https://doi.org/10.1016/S1473-3099(07)70210-4\u003c/li\u003e\n\u003cli\u003eWilkes JC, Nelson JD, Worthen HG, Morris M, Hogg RJ (1982). Response to pneumococcal vaccination in children with nephrotic syndrome. American Journal of Kidney Diseases, 2(1), 43\u0026ndash;46. https://doi.org/10.1016/S0272-6386(82)80042-5\u003c/li\u003e\n\u003cli\u003eTejani A, Fikrig S, Schiffman G, Gurumurthy K (1984). Persistence of protective pneumococcal antibody following vaccination in patients with the nephrotic syndrome. American Journal of Nephrology, 4(1), 32\u0026ndash;37. https://doi.org/10.1159/000166769\u003c/li\u003e\n\u003cli\u003eGarin EH, Barrett DJ (1988). Pneumococcal polysaccharide immunization in patients with active nephrotic syndrome. Nephron, 50(4), 383\u0026ndash;388. https://doi.org/10.1159/000185210\u003c/li\u003e\n\u003cli\u003eYıldız N, Yavaşcan \u0026Ouml;, Anarat A, Akman S, Ko\u0026ccedil;ak G, Kara OD, Aydın M, D\u0026uuml;ş\u0026uuml;nsel R, Erdoğan H, G\u0026uuml;rg\u0026ouml;ze MK, Kılı\u0026ccedil; BD, Kocamaz H, \u0026Ouml;z\u0026ccedil;elik G, \u0026Ouml;z\u0026ccedil;elik A, \u0026Ouml;z\u0026ccedil;elik Z, \u0026Ouml;z\u0026ccedil;elik Z, \u0026Ouml;z\u0026ccedil;elik Z (2013). Hepatitis B virus vaccination in children with steroid sensitive nephrotic syndrome: Immunogenicity and safety? Vaccine, 31(29), 3309\u0026ndash;3312. https://doi.org/10.1016/j.vaccine.2013.05.004\u003c/li\u003e\n\u003cli\u003eRose MA, Buess J, Ventur Y, Zielen S, Herrmann E, Schulze J, Schubert R (2013). Reference ranges and cutoff levels of pneumococcal antibody global serum assays (IgG and IgG2) and specific antibodies in healthy children and adults. Medical Microbiology and Immunology, 202(4), 285\u0026ndash;294. https://doi.org/10.1007/s00430-013-0292-3\u003c/li\u003e\n\u003cli\u003eKemper MJ, Altrogge H, Ganschow R, M\u0026uuml;ller-Wiefel DE (2002). Serum levels of immunoglobulins and IgG subclasses in steroid sensitive nephrotic syndrome. Pediatric Nephrology, 17(6), 413\u0026ndash;417. https://doi.org/10.1007/s00467-001-0817-7\u003c/li\u003e\n\u003cli\u003eHeslan JM, Nguyen Khoa T, Mougenot B, Desch\u0026ecirc;nes G, Bensman A (1982). Impaired IgG synthesis in patients with the nephrotic syndrome. Clinical Nephrology, 18(3), 144\u0026ndash;147.\u003c/li\u003e\n\u003cli\u003eLopez B, Bahuaud M, Fieschi C, Mehlal S, Jeljeli M, Rogeau S, Brabant S, Deleplancque AS, Dubucquoi S, Poizot S, Terriou L, Launay D, Batteux F, Labalette M, Lef\u0026egrave;vre G (2017). Value of the overall pneumococcal polysaccharide response in the diagnosis of primary humoral immunodeficiencies. Frontiers in Immunology, 8, 1862. https://doi.org/10.3389/fimmu.2017.01862\u003c/li\u003e\n\u003cli\u003eSchauer U, Stemberg F, Rieger CHL, B\u0026uuml;ttner W, Borte M, Schubert S, Riedel F, Herz U, Renz H, Wick M, Rieger C (2003). IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with The Binding Site reagents. Clinical Chemistry, 49(11), 1924\u0026ndash;1929. https://doi.org/10.1373/clinchem.2003.022350\u003c/li\u003e\n\u003cli\u003eSiber GR, Chang I, Baker S, Fernsten P, O\u0026apos;Brien KL, Santosham M, Reid GR, Thompson C, Madore D, Kohberger R, Hackell J, Paradiso PR (2007). Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine, 25(19), 3816\u0026ndash;3826. https://doi.org/10.1016/j.vaccine.2007.01.119\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Children, Idiopathic nephrotic syndrome, Pneumococcal infection, Vaccination, Immunogenicity","lastPublishedDoi":"10.21203/rs.3.rs-6933268/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6933268/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDue to secondary immunodeficiency, idiopathic nephrotic syndrome in children increases the risk of invasive pneumococcal disease. This study compares pneumococcal vaccine antibody responses in children with idiopathic nephrotic syndrome to healthy controls. We also investigated the effects of relapse frequency and corticosteroid dose on antibody levels in children with idiopathic nephrotic syndrome.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe study included 30 children with corticosteroid-responsive minimal change nephrotic syndrome and 24 healthy children. All children participating in the study were vaccinated with the 23-valent pneumococcal polysaccharide vaccine.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePositive vaccine response (at least a 2-fold increase in polysaccharide anti-pneumococcal IgG titers) rates and the titer change rates were similar between patients and healthy subjects. Moreover, the rates of a four-fold increase were comparable between the two groups. Additionally, relapse rate and corticosteroid doses in patients did not impact pre- and post-vaccination antibody titers. No adverse events were observed during the study.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe 23-valent pneumococcal polysaccharide vaccine is safe and elicits a robust immune response in children with idiopathic nephrotic syndrome, comparable to that of healthy children. The response also was unaffected by disease relapses or cumulative corticosteroid dose. Larger cohorts and antibody protection duration are needed for the vaccine response investigation.\u003c/p\u003e","manuscriptTitle":"Immunogenicity of the 23-Valent Polysaccharide Pneumococcal Vaccine in Children with Idiopathic Nephrotic Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-24 12:40:07","doi":"10.21203/rs.3.rs-6933268/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2025-07-28T18:02:49+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-06-22T03:54:55+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-20T13:17:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-20T07:14:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-06-19T13:23:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a3e5c893-5f93-456d-82e3-917025a544b4","owner":[],"postedDate":"June 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-24T15:59:58+00:00","versionOfRecord":{"articleIdentity":"rs-6933268","link":"https://doi.org/10.1007/s00467-025-07026-3","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-11-19 15:57:04","publishedOnDateReadable":"November 19th, 2025"},"versionCreatedAt":"2025-06-24 12:40:07","video":"","vorDoi":"10.1007/s00467-025-07026-3","vorDoiUrl":"https://doi.org/10.1007/s00467-025-07026-3","workflowStages":[]},"version":"v1","identity":"rs-6933268","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6933268","identity":"rs-6933268","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}