Immunohistochemical Expression of Programmed death-ligand 1 (PD-L1) in Lesional Psoriatic Skin: A Study of Its Role in Psoriasis Pathogenesis

Immunohistochemical Expression of Programmed death-ligand 1 (PD-L1) in Lesional Psoriatic Skin: A Study of Its Role in Psoriasis Pathogenesis | 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 Immunohistochemical Expression of Programmed death-ligand 1 (PD-L1) in Lesional Psoriatic Skin: A Study of Its Role in Psoriasis Pathogenesis Ali Mohamed Ayaad, Azza Samy Amer, May Mostafa Abo EL-Kher, Shaimaa Abdelraouf Elgohary This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7435479/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Psoriasis is a chronic, immune-mediated inflammatory disorder in which persistent T-cell activation by antigen-presenting cells (APCs) and defects in immune tolerance contribute to disease development, similar to other autoimmune conditions. Programmed death-1 (PD-1) is an inhibitory co-receptor that regulates inflammation and supports peripheral immune tolerance. Dysfunction of the PD-1/PD-L1 pathway is thought to play a significant role in the pathogenesis of various immune-mediated diseases. The objective of this study was to investigate the expression of Programmed death-ligand 1 (PD-L1) in psoriasis through its immunohistochemical (IHC) expression in involved skin in psoriatic cases. This prospective case control study was conducted on 30 skin biopsies of patients with plaque psoriasis and 20 biopsies of sex and age matched individuals as control group. Immunohistochemical staining using monoclonal mouse antibody against PDL-1(22C3) was applied on skin biopsy specimens obtained from both patient and control groups. There was a high statistically significant difference (p-value < 0.001) between both groups as regard PDL1 expression. In patient’s group, 30% of specimens were with low expression and 70% of specimens with high expression (80% low expression & 20% high expression in control group). A statistically significant and strong inverse correlation was observed between the number of PD-L1(+) immune cells and PASI scores (P < 0.001, r = − 0.77). Furthermore, the number of PD-L1(+) immune cells demonstrated a statistically significant negative correlation with disease duration (P = 0.02, r = − 0.42). In conclusion, PD-L1 expression in immune cells was significantly higher compared to healthy controls, indicating a potential role of PD-L1 in the disease pathogenesis. Psoriasis Immunohistochemistry PD-L1 Immunotherapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Psoriasis is a chronic, recurring, immune-mediated inflammatory skin condition that affects millions of individuals globally [ 1 ]. Psoriasis has a complex etiology, with a strong genetic predisposition leading to disease risk [ 2 ]. Environmental factors, including psychological stress, physical trauma (referred to as the Köbner phenomenon), and lifestyle choices like smoking, significantly affect disease expression [ 3 ]. Psoriasis has a complicated pathophysiology that is still poorly understood despite extensive research. Although its precise source is yet unknown, sustained activation of T-cells by antigen-presenting cells (APCs) is one of the key phenomena in the immune response's operation in psoriasis. Psoriasis and many other immune-mediated disorders are thought to occur as a result of disruptions in immuno-tolerance processes, according to a number of theories [ 4 ]. New molecules and pathways have been identified as influencing autoimmunity and tolerance. Among these molecules, programmed death-1 (PD-1) (CD279) functions as an immune checkpoint that transmits inhibitory signals, helping to regulate T-cell activation and preserve self-tolerance within peripheral tissues [ 5 ]. PD-1 is expressed by activated T, B, and natural killer (NK) cells, as well as macrophages, dendritic cells (DCs), and monocytes [ 6 ], and downregulates the human immune response through its interaction with two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) [ 7 ]. PD-L1 and PD-L2 are a part of the B7 family of T cell co-inhibitory molecules [ 8 ]. PD-L1 is widely expressed on B cells, T cells, dendritic cells, and macrophages; PD-L2 is primarily expressed on activated dendritic cells and macrophages [ 5 ]. Binding of PD-1 to PD-L1 or PD-L2 triggers inhibitory signaling that dampens T-cell activation, promotes immune tolerance, and preserves immunological homeostasis. Consequently, PD-1 plays a protective role by suppressing autoimmunity and preventing the onset of autoimmune diseases [ 9 ]. Several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, type 1 diabetes, and encephalomyelitis, have been associated with reduced expression of PD-1 and its ligands [ 10 ]. Furthermore, PD-1 inhibitors have demonstrated remarkable therapeutic benefits in cancer patients. However, over half of treated individuals develop immune-related adverse events (irAEs), with cutaneous manifestations often appearing early. These skin-related irAEs include psoriasis, lichenoid dermatitis, vitiligo, dermatomyositis, pemphigus, aspergillosis, severe drug eruptions, and non-specific rashes. Psoriasis, as a cutaneous irAE induced by PD-1 inhibition, may present either as a new-onset condition (55.0%) or as an exacerbation of pre-existing psoriatic lesions [ 11 ]. The observation that anti-PD-1/PD-L1 antibodies can induce psoriasis supports the involvement of the PD-1/PD-L1 pathway in the disease pathogenesis. While a limited number of studies have investigated PD-1 and PD-L1 expression in peripheral blood T cells of psoriasis patients, even fewer have explored their expression within psoriatic skin lesions. So, the current study aimed to investigate the expression of PD-L1 in psoriasis through its immunohistochemical (IHC) expression in involved skin in psoriatic cases. Subjects and methods Participants This prospective case control study was conducted on 30 skin biopsies of patients with plaque psoriasis and 20 biopsies of sex and age matched individuals as control group. Patients were randomly recruited from the Dermatology Outpatient Clinic at Al-Zahraa University Hospital. The healthy controls were chosen from individuals with no apparent health problems who were attending the Plastic Surgery Department. The study was done after approval of research ethical committee of Faculty of Medicine for Girls, Al-Azhar University (Approval No. 2025022673) and written informed consent was obtained from all participants. Patients included were adults over 18 years of age, of both sexes, with chronic plaque psoriasis for at least one year, who had not received any specific systemic treatment for a minimum of 4 weeks prior to the study and Psoriasis Area and Severity Index (PASI) score > 5. Pregnant and lactating patients or Patients with autoimmune diseases such as systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, type 1 diabetes mellitus, inflammatory bowel disease, encephalomyelitis, vitiligo or alopecia areata, as well as those with chronic systemic conditions like chronic renal failure or hepatic insufficiency, were excluded. In addition, individuals with any malignancy or those receiving anti-PD-1 therapy for malignancy were also excluded. All patients in this study were subjected to detailed history taking, general examination (to exclude systemic diseases) and dermatological examination to determine the extent and distribution of the disease. Nail and scalp affection were evaluated. Psoriasis Area and Severity Index (PASI) score was used to evaluate the severity of psoriasis in patients. Disease severity was categorized according to PASI severity scores (range 0–72) as follows: Mild: if PASI ranged between 0 and 5, Moderate: if exceed 5 to 12, Severe: more than 12 up to 20, while if it was > 20, it was considered Very Severe [ 12 ]. Skin biopsy: The biopsy site was sterilized with 75% alcohol, and local anesthesia was administered using xylocaine injected into the target area. A 4 mm punch biopsy was obtained from psoriatic lesions in patients and from normal skin in healthy controls, then preserved in 10% buffered formalin. All specimens were submitted to the Pathology Department, where they were dehydrated through ascending ethanol concentrations, cleared in xylene, and embedded in paraffin. From each block, several 5 µm-thick sections were prepared. One section was stained with Hematoxylin and Eosin (H&E) for routine histopathological evaluation, while additional sections were mounted on positively charged slides and stored at room temperature for subsequent immunohistochemical staining of PD-L1. Immunohistochemical Study Procedure: For immunohistochemical (IHC) analysis, tissue blocks were sectioned at 5 µm thickness and mounted onto positively charged slides (Superfrost Plus, Menzel-Gläser, Germany). PD-L1 IHC staining was carried out on Dako 48 link autostainer using PD-L1 22c3 dako dnemark, Heat induced antigen retrieval was used for 30 min at 97°C in the high-PH EnVision™ FLEX Target Retrieval Solution and the primary antibody was used at a dilution of 1 in 100. Analysis of the Immunohistochemical Study Results Positive PD-L1 (22c3) IHC expression was assessed in immune cells (ICs) as punctate, cytoplasmic, or membrane staining at any intensity. The positively stained ICs in each case were examined, counted, and documented blindly by two authors. Cases with discordant scores were reexamined by the two authors using a multihead microscope in order to reach the proper scoring. Based on their PD-L1 positive immune cell counts, cases were categorized into two groups, as defined by Emre et al. [5] : Cases were divided into two groups: those with high PD-L1–positive immune cell counts (≥ 10 PD-L1–positive ICs) and those with low PD-L1–positive immune cell counts (< 10 PD-L1–positive ICs). Statistical analysis: Data were analyzed using Statistical Program for Social Science (SPSS) version 24. Qualitative variables were presented as frequencies and percentages, while quantitative variables were expressed as mean ± standard deviation (SD). The mean represents the average value, calculated as the sum of all observations divided by the number of observations. The standard deviation (SD) reflects the degree of variability within the dataset; a low SD indicates that values are clustered closely around the mean, whereas a high SD suggests that the values are more widely dispersed. The following tests were done independent sample T test (T), Chi-square test and probability (P-value). P-value < 0.05 was considered significant. Results The mean age of the patients was 47.3 ± 13.7 with range of 19–70 years while in control group, the mean age was 44.8 ± 13.4 with range of 19–64. Among the patients in the study, 17 were males (56.7%) and 13 were females (43.3%) compared to 10 males (50%) and 10 females (50%) in control group. There was no significant difference between the two groups as regard age and sex (p-value = 0.531 & 0.643 respectively) (Table 1). Table (2) shows the description of clinical data in patient’s group. As regard duration , the mean disease duration of all studied patients was 13.9 ± 10.2 years with minimum duration of 1 year and maximum duration of 40 years. As regard PASI score , the mean score of all studied patients was 17.9 ± 8.4 years with minimum score of 6 and maximum score of 41.7. There were 10 patients (33.3%) with moderate psoriasis, 9 patients (30%) with severe psoriasis and 11 patients (36.7%) with very severe disease. Table (3) shows a high statistically significant difference (p-value < 0.001) between studied groups as regard PDL1 expression in the dermis while no PD-L1 expression was observed in the keratinocytes in psoriatic skin and healthy controls. In patient’s group, there were 9 specimens (30%) of low expression and 21 specimens (70%) of high expression while in control group, there were 16 specimens (80%) of low expression and only 4 (20%) were with high expression (Fig. 1, Fig. 2). Additionally, there was a high statistically significant (p-value < 0.001) increased number of positive cells in patient’s group (mean = 24.5 ± 16.9, range = 2–70) when compared with control group (mean = 6.05 ± 4.9, range = 1–18) Table (4) shows statistically significant (p-value = 0.02) negative correlation (r = − 0.42) between PDL1 expression and duration of psoriasis (Fig. 3). Moreover, there was high statistically significant (p-value < 0.001) negative correlation (r = − 0.77) between PDL1 expression and PASI score (Fig. 4). While there was no statistically significant correlation (p-value = 0.081) between PDL1 expression and age. Discussion Psoriasis is generally recognized as a Th1- and Th17-driven disease. In psoriasis vulgaris, cytokines from the Th1 axis (IL-12, IFN-γ, IL-12) and the Th17 pathway (IL-17F, IL-17A, IL-22, IL-21) recruit immune cells, resulting in continuous inflammation and keratinocyte proliferation [ 13 ]. Both PD-1 and PD-L 1 are often expressed by T-cells, and Anti-PD-1 antibody therapy markedly modifies T-cell–mediated adaptive immune responses, which is widely regarded as the primary mechanism underlying the onset or exacerbation of psoriasis associated with PD-1 blockade [ 11 ]. Only a limited number of studies have examined PD-1 and PD-L1 expression in psoriatic lesional skin, and their findings have been inconsistent [ 5 ]. So, the current study was conducted to investigate the expression of PD-L1 in psoriasis through its immunohistochemical (IHC) expression in involved skin in psoriatic cases. The present study showed a high statistically significant difference (p-value < 0.001) between studied groups as regard PDL1 expression in the dermis while no PD-L1 expression in the keratinocytes was observed in psoriatic skin and healthy controls. In patient’s group, there were 70% of patients with high expression and 30% with low expression while in control group, the majority of specimens (80%) of low expression and only 20% of high expression. Additionally, there was a high statistically significant (p-value < 0.001) increased number of positive cells in patient’s group when compared with control group; suggesting that disruption of the PD-1/PD-L1 axis may contribute to psoriasis pathogenesis. In the future, therapies targeting the PD-1/PD-L1 pathway could represent an emerging therapeutic option for psoriasis. Given that PD-1 is an immune system inhibitor co-receptor, it could seem illogical that autoimmune illnesses would lead to an increase in its expression. Nevertheless, study findings indicate that the PD-1/PD-L1 pathway is altered in chronic inflammatory diseases such as SLE and rheumatoid arthritis. Additionally, it has been suggested that PD-1 and/or its ligand dysfunction may play a significant role in the persistent hyperactivity of the T-cell-mediated immune response seen in a variety of autoimmune disorders such as psoriasis [ 14 ]. Given that T cell immunity plays a key role in the pathophysiology of psoriasis and that T cells frequently express PD-1 and PD-L1 [ 11 ], this could explain a higher expression of PDL1 in psoriasis. Also, this may reflect an attempt at immune regulation to control T-cell activation. The discrepancy between dermal and epidermal PD-L1 expression suggested compartment-specific immune dysregulation in psoriasis. Since upregulation of PD-L1 in the dermis suggests an attempt at immune regulation in the dermis to control T-cell activation, absence of PD-L1 in the epidermis implies a failure of the epidermal compartment to engage immune checkpoints; contributing to persistent activation of T cells and chronic unregulated inflammatory characteristics. Our results were in agreement with Emre et al. [ 5 ] who demonstrated that PD-1 and PD-L1 expression in immune cells of dermal psoriatic skin was significantly higher compared with healthy controls, while neither psoriatic nor healthy keratinocytes showed PD-1 or PD-L1 expression. Furthermore, Kim et al. [ 15 ] reported that, relative to normal skin and other inflammatory dermatoses such as pityriasis rosea, lichen planus, and allergic contact dermatitis, keratinocyte PD-L1 expression was markedly reduced in psoriatic epidermis. They proposed that the lack of PD-1 ligands may promote enhanced T-cell–mediated inflammation and reduced Treg activity, both characteristic features of psoriasis, thereby highlighting the role of keratinocytes as central amplifiers and sustainers of psoriatic inflammation. In contrast tom our results, Du et al. [ 16 ] observed in the majority of cases of oral lichen planus (OLP), PD-L1 and PD-L2 were both highly expressed on keratinocytes and weakly on the infiltrating T lymphocytes in the subepithelium. They proposed that the pathologically altered mucosal immunological milieu, which prevents T cell proliferation and rebalances local immune responses, may be the cause of the elevated expression of PD-L in OLP patients' mucosa. As regard the correlation study between PDL1 expression and other studied data in patients, there was a high statistically significant negative correlation between PDL1 expression and PASI score. Decreased PASI score in patients with high expression when compared with patients of low expression. This could be explained as PD-L1 as an Immunoregulatory Brake -via binding to PD-1 on T cells- resulting in inhibition of T-cell activation and suppressing immune responses. So, high PD-L1 expression might be a compensatory mechanism to dampen excessive inflammation. Therefore, when PD-L1 is more expressed, it may limit further immune-mediated damage, resulting in lower severity scores. Moreover, when PD-L1 expression is reduced or absent, this allows uncontrolled inflammation and more severe disease. While there was no statistically significant correlation between PDL1 expression and age in the present study. In addition, there was a statistically significant negative correlation between PDL1 expression and duration of psoriasis. This could be explained as psoriasis becomes more chronic, there may be progressive reduction in immune check point activity (reduced PD-L1 expression). This may be due to immune exhaustion or desensitization. In agreement to our results of correlation to PASI score, Emre et al. [ 5 ] reported a significant negative correlation between PD-L1(+) immune cell counts and PASI scores, whereas no correlation was found with disease duration. The discrepancies among study findings may be attributed to the limited sample sizes or to variations in PD-1 and PD-L1 expression patterns between the epidermis and dermis. Conclusion PD-L1 expression in immune cells within psoriatic skin is significantly elevated compared to that in healthy controls. It may play a key role in reducing the regulation of ineffective or harmful immune responses and maintaining immune tolerance. In the future, PD-1/PD-L1 pathway can be ideal treatment targets for psoriasis patients and medications modulating this pathway may be another promising option in therapy of psoriasis. Declarations Fund: This work didn’t receive any fund from government or non-government institutions Author Contribution ِAzza Samy conceived and designed the study, recruited patients, and supervised the clinical work. May Mostafa contributed to patient evaluation, clinical data collection, and manuscript drafting. Ali Ayaad performed the histopathological examination, conducted and scored the PD-L1 immunohistochemistry. Shaimaa Elgohary validated the immunohistochemical results, contributed to data analysis, and prepared pathology figures. All authors interpreted the data, revised the manuscript critically for important intellectual content, and approved the final version for submission. Data Availability the data that support the findings of this study are available from the corresponding author upon reasonable request. References Brezinski EA, Dhillon JS, Armstrong AW (2015) Economic burden of psoriasis in the United States: A systematic review. JAMA Dermatol 151:651–658. https://doi.org/10.1001/jamadermatol.2014.3593 Mateu-Arrom L, Puig L (2023) Genetic and epigenetic mechanisms of psoriasis. Genes 14:1619. https://doi.org/10.3390/genes14081619 Suzuki T, Ito T, Gilhar A, Bertolini M, Paus R (2022) The hair follicle-psoriasis axis: Shared regulatory mechanisms and therapeutic targets. Exp Dermatol 31:266–279. https://doi.org/10.1111/exd.14535 Deng Y, Chang C, Lu Q (2016) The inflammatory response in psoriasis: A comprehensive review. Clin Rev Allergy Immunol 50:377–389. https://doi.org/10.1007/s12016-016-8535-x Emre S, Süngü N, Hayran Y, Dursun R, Aşkın Ö, Ergun T (2023) Investigation of the PD-1/PD-L1 expression in the lesional skins of patients with psoriasis. Dermatol Pract Concept 13:e2023134. https://doi.org/10.5826/dpc.1302a134 Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, Rosenberg SA (2009) Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114:1537–1544. https://doi.org/10.1182/blood-2008-12-195792 Lin X, Kang K, Chen P, Liu W, Mo Y, Zeng H, Zhang Y (2024) Regulatory mechanisms of PD-1/PD-L1 in cancers. Mol Cancer 23:108. https://doi.org/10.1186/s12943-024-01973-5 Liang SC, Latchman YE, Buhlmann JE, Tomczak MF, Horwitz BH, Freeman GJ, Sharpe AH (2003) Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol 33:2706–2716. https://doi.org/10.1002/eji.200324228 Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034. https://doi.org/10.1084/jem.192.7.1027 Zamani RM, Aslani S, Salmaninejad A, Javan MR, Rezaei R (2016) PD-1/PD-L and autoimmunity: A growing relationship. Cell Immunol 310:27–41. https://doi.org/10.1016/j.cellimm.2016.09.004 Wan Z, Huang J, Ou X, Wang M, Li X, Deng H, Lu T (2024) Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. Bras Dermatol 99:425–432. https://doi.org/10.1016/j.abd.2023.02.010 Strober B, Karki C, Mason M, Guo Y, Alemao E, Pillai R, Reich K (2017) Impact of Psoriasis Area and Severity Index (PASI) on patient-reported outcomes in patients with psoriasis: Results from the Corrona Psoriasis Registry. J Am Acad Dermatol 76:AB406. https://doi.org/10.1016/j.jaad.2016.12.155 Chong HT, Kopecki Z, Cowin AJ (2013) Lifting the silver flakes: The pathogenesis and management of chronic plaque psoriasis. Biomed Res Int 2013:168321. https://doi.org/10.1155/2013/168321 Adamczyk M, Krasowska D (2021) PD-1/PD-L1 pathway in psoriasis and psoriatic arthritis: A review. Adv Dermatol Allergol 38:925–930. https://doi.org/10.5114/ada.2020.98239 Kim DS, Je JH, Kim SH, Seo YJ, Kim CD, Lee JH (2015) Programmed death-ligand 1, 2 expressions are decreased in the psoriatic epidermis. Arch Dermatol Res 307:531–538. https://doi.org/10.1007/s00403-015-1559-3 Du GH, Qin XP, Li Q, Sun YX, Zhang ZY (2011) The high expression level of programmed death-1 ligand 2 in oral lichen planus and the possible costimulatory effect on human T cells. J Oral Pathol Med 40:525–532. https://doi.org/10.1111/j.1600-0714.2011.01025.x Tables Table (1): Comparison between studied groups regarding age and sex. Patients (N = 30) Control (N = 20) Stat. test P-value Age (years) Mean ±SD 47.3 ± 13.7 44.8 ± 13.4 T = 0.63 0.531 NS Range 19 - 70 19 – 64 Sex Male 17 56.7% 10 50% X 2 = 0.21 0.643 NS Female 13 43.3% 10 50% T: independent sample T test. X 2 : Chi-square test. NS: p-value > 0.05 is considered non-significant. Table (2): Description of clinical data in patient’s group. Patient’s group (N = 30) Duration (years) Mean ±SD 13.9 ± 10.2 Min - Max 1 – 40 PASI score Mean ±SD 17.9 ± 8.4 Min - Max 6 – 41.7 PASI score categories Moderate 10 33.3% Severe 9 30% Very severe 11 36.7% No: number, SD: Standard deviation, PASI: Psoriasis Area and Severity Index Table (3): Comparison of PDL1 expression and Number of positive cells between studied groups. Patients (N = 30) Control (N = 20) Stat. test P-value No of positive cells Mean ±SD 24.5 ± 16.9 6.05 ± 4.9 T = 4.7 < 0.001 HS Range 2 - 70 1 – 18 PDL1 expression Low 9 30% 16 80% X 2 = 12 < 0.001 HS High 21 70% 4 20% T: independent sample T test. HS: p-value < 0.001 is considered highly significant. X 2 : Chi-square test. Table (4): Correlation study between PDL1 expression and other studied data in patient’s group . PDL1 expression Pearson correlation coefficient r p-value Age -0.32 0.081 Duration -0.42 0.02 * PASI score -0.77 < 0.001 ** (r): Pearson correlation coefficient. *: p-value < 0.05 is considered significant. **: p-value 0.05 is considered non-significant. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 23 Nov, 2025 Reviews received at journal 20 Nov, 2025 Reviews received at journal 09 Nov, 2025 Reviewers agreed at journal 03 Nov, 2025 Reviewers agreed at journal 30 Oct, 2025 Reviewers invited by journal 28 Oct, 2025 Editor assigned by journal 25 Aug, 2025 Submission checks completed at journal 25 Aug, 2025 First submitted to journal 22 Aug, 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. 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05:39:02","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":82830,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7435479/v1/e9fa24635a150918faaca358.html"},{"id":95529637,"identity":"e6040786-c6b4-4605-99ff-99bb5365fdd5","added_by":"auto","created_at":"2025-11-10 10:17:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16454519,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea) \u003c/strong\u003eA case of psoriasis revealed positive PD-L1 (22C3) staining observed in more than 10 immune cells (ICs) within the upper dermis beneath the epidermis (x100). \u003cstrong\u003eb)\u003c/strong\u003e High power view of the previous case revealed positive PD-L1 (22C3) membranous and cytoplasmic staining of ICs and no significant expression is detected in the overlying epidermal keratinocytes (x400). \u003cstrong\u003ec) \u003c/strong\u003eAnother case of psoriasis revealed positive PD-L1 (22C3) staining in more than 10 ICs within the upper dermis (x200). \u003cstrong\u003ed)\u003c/strong\u003eHigh power view of the previous case revealed positive PD-L1 (22C3) membranous and cytoplasmic staining of ICs and no significant PD-L1 expression is detected in the overlying epidermal keratinocytes (x400).\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7435479/v1/b2337945d7baa68c49227081.png"},{"id":95503362,"identity":"a1a6cea4-f9a7-4d4f-9f79-ad8fc547e4be","added_by":"auto","created_at":"2025-11-10 05:39:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":6565703,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea)\u003c/strong\u003e A skin of control group revealed negative PD-L1 (22C3) staining (x200). \u003cstrong\u003eb)\u003c/strong\u003eHigh power of the previous case revealed negative PD-L1 (22C3) staining (x400).\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7435479/v1/c9f05ca2755016446e3da670.png"},{"id":95503359,"identity":"472c354d-8467-4170-9afa-c3626e2c6197","added_by":"auto","created_at":"2025-11-10 05:39:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3543704,"visible":true,"origin":"","legend":"\u003cp\u003eNegative correlation between PDL1 expression and duration in patient’s group.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-7435479/v1/1472de12c012d8a192045347.png"},{"id":95503361,"identity":"e71f16dd-52ec-4f06-883f-0eb7b1fefcc0","added_by":"auto","created_at":"2025-11-10 05:39:02","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":515201,"visible":true,"origin":"","legend":"\u003cp\u003eNegative correlation between PDL1 expression and PASI score in patient’s group.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-7435479/v1/0605784b363f2eaea226b42d.png"},{"id":95654006,"identity":"6382150f-2abb-496b-ba57-7a3196d50db8","added_by":"auto","created_at":"2025-11-11 16:08:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":24441937,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7435479/v1/14fdc939-021b-4194-adda-3eb818becec4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immunohistochemical Expression of Programmed death-ligand 1 (PD-L1) in Lesional Psoriatic Skin: A Study of Its Role in Psoriasis Pathogenesis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePsoriasis is a chronic, recurring, immune-mediated inflammatory skin condition that affects millions of individuals globally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Psoriasis has a complex etiology, with a strong genetic predisposition leading to disease risk [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Environmental factors, including psychological stress, physical trauma (referred to as the K\u0026ouml;bner phenomenon), and lifestyle choices like smoking, significantly affect disease expression [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePsoriasis has a complicated pathophysiology that is still poorly understood despite extensive research. Although its precise source is yet unknown, sustained activation of T-cells by antigen-presenting cells (APCs) is one of the key phenomena in the immune response's operation in psoriasis. Psoriasis and many other immune-mediated disorders are thought to occur as a result of disruptions in immuno-tolerance processes, according to a number of theories [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNew molecules and pathways have been identified as influencing autoimmunity and tolerance. Among these molecules, programmed death-1 (PD-1) (CD279) functions as an immune checkpoint that transmits inhibitory signals, helping to regulate T-cell activation and preserve self-tolerance within peripheral tissues [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. PD-1 is expressed by activated T, B, and natural killer (NK) cells, as well as macrophages, dendritic cells (DCs), and monocytes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and downregulates the human immune response through its interaction with two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePD-L1 and PD-L2 are a part of the B7 family of T cell co-inhibitory molecules [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. PD-L1 is widely expressed on B cells, T cells, dendritic cells, and macrophages; PD-L2 is primarily expressed on activated dendritic cells and macrophages [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Binding of PD-1 to PD-L1 or PD-L2 triggers inhibitory signaling that dampens T-cell activation, promotes immune tolerance, and preserves immunological homeostasis. Consequently, PD-1 plays a protective role by suppressing autoimmunity and preventing the onset of autoimmune diseases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, type 1 diabetes, and encephalomyelitis, have been associated with reduced expression of PD-1 and its ligands [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFurthermore, PD-1 inhibitors have demonstrated remarkable therapeutic benefits in cancer patients. However, over half of treated individuals develop immune-related adverse events (irAEs), with cutaneous manifestations often appearing early. These skin-related irAEs include psoriasis, lichenoid dermatitis, vitiligo, dermatomyositis, pemphigus, aspergillosis, severe drug eruptions, and non-specific rashes. Psoriasis, as a cutaneous irAE induced by PD-1 inhibition, may present either as a new-onset condition (55.0%) or as an exacerbation of pre-existing psoriatic lesions [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe observation that anti-PD-1/PD-L1 antibodies can induce psoriasis supports the involvement of the PD-1/PD-L1 pathway in the disease pathogenesis. While a limited number of studies have investigated PD-1 and PD-L1 expression in peripheral blood T cells of psoriasis patients, even fewer have explored their expression within psoriatic skin lesions. So, the current study aimed to investigate the expression of PD-L1 in psoriasis through its immunohistochemical (IHC) expression in involved skin in psoriatic cases.\u003c/p\u003e"},{"header":"Subjects and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003eThis prospective case control study was conducted on 30 skin biopsies of patients with plaque psoriasis and 20 biopsies of sex and age matched individuals as control group. Patients were randomly recruited from the Dermatology Outpatient Clinic at Al-Zahraa University Hospital. The healthy controls were chosen from individuals with no apparent health problems who were attending the Plastic Surgery Department. The study was done after approval of research ethical committee of Faculty of Medicine for Girls, Al-Azhar University (Approval No. 2025022673) and written informed consent was obtained from all participants.\u003c/p\u003e\u003cp\u003ePatients included were adults over 18 years of age, of both sexes, with chronic plaque psoriasis for at least one year, who had not received any specific systemic treatment for a minimum of 4 weeks prior to the study and Psoriasis Area and Severity Index (PASI) score\u0026thinsp;\u0026gt;\u0026thinsp;5. Pregnant and lactating patients or Patients with autoimmune diseases such as systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, type 1 diabetes mellitus, inflammatory bowel disease, encephalomyelitis, vitiligo or alopecia areata, as well as those with chronic systemic conditions like chronic renal failure or hepatic insufficiency, were excluded. In addition, individuals with any malignancy or those receiving anti-PD-1 therapy for malignancy were also excluded.\u003c/p\u003e\u003cp\u003eAll patients in this study were subjected to detailed history taking, general examination (to exclude systemic diseases) and dermatological examination to determine the extent and distribution of the disease. Nail and scalp affection were evaluated.\u003c/p\u003e\u003cp\u003ePsoriasis Area and Severity Index (PASI) score was used to evaluate the severity of psoriasis in patients. Disease severity was categorized according to PASI severity scores (range 0\u0026ndash;72) as follows: Mild: if PASI ranged between 0 and 5, Moderate: if exceed 5 to 12, Severe: more than 12 up to 20, while if it was \u0026gt;\u0026thinsp;20, it was considered Very Severe [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSkin biopsy:\u003c/h3\u003e\n\u003cp\u003eThe biopsy site was sterilized with 75% alcohol, and local anesthesia was administered using xylocaine injected into the target area. A 4 mm punch biopsy was obtained from psoriatic lesions in patients and from normal skin in healthy controls, then preserved in 10% buffered formalin. All specimens were submitted to the Pathology Department, where they were dehydrated through ascending ethanol concentrations, cleared in xylene, and embedded in paraffin. From each block, several 5 \u0026micro;m-thick sections were prepared. One section was stained with Hematoxylin and Eosin (H\u0026amp;E) for routine histopathological evaluation, while additional sections were mounted on positively charged slides and stored at room temperature for subsequent immunohistochemical staining of PD-L1.\u003c/p\u003e\n\u003ch3\u003eImmunohistochemical Study Procedure:\u003c/h3\u003e\n\u003cp\u003eFor immunohistochemical (IHC) analysis, tissue blocks were sectioned at 5 \u0026micro;m thickness and mounted onto positively charged slides (Superfrost Plus, Menzel-Gl\u0026auml;ser, Germany). PD-L1 IHC staining was carried out on Dako 48 link autostainer using PD-L1 22c3 dako dnemark, Heat induced antigen retrieval was used for 30 min at 97\u0026deg;C in the high-PH EnVision\u0026trade; FLEX Target Retrieval Solution and the primary antibody was used at a dilution of 1 in 100.\u003c/p\u003e\n\u003ch3\u003eAnalysis of the Immunohistochemical Study Results\u003c/h3\u003e\n\u003cp\u003ePositive PD-L1 (22c3) IHC expression was assessed in immune cells (ICs) as punctate, cytoplasmic, or membrane staining at any intensity. The positively stained ICs in each case were examined, counted, and documented blindly by two authors. Cases with discordant scores were reexamined by the two authors using a multihead microscope in order to reach the proper scoring.\u003c/p\u003e\u003cp\u003eBased on their PD-L1 positive immune cell counts, cases were categorized into two groups, as defined by Emre et al. \u003csup\u003e[5]\u003c/sup\u003e: Cases were divided into two groups: those with high PD-L1\u0026ndash;positive immune cell counts (\u0026ge;\u0026thinsp;10 PD-L1\u0026ndash;positive ICs) and those with low PD-L1\u0026ndash;positive immune cell counts (\u0026lt;\u0026thinsp;10 PD-L1\u0026ndash;positive ICs).\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis:\u003c/h2\u003e\u003cp\u003eData were analyzed using Statistical Program for Social Science (SPSS) version 24. Qualitative variables were presented as frequencies and percentages, while quantitative variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). The mean represents the average value, calculated as the sum of all observations divided by the number of observations. The standard deviation (SD) reflects the degree of variability within the dataset; a low SD indicates that values are clustered closely around the mean, whereas a high SD suggests that the values are more widely dispersed. The following tests were done independent sample T test (T), Chi-square test and probability (P-value). P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean age of the patients was 47.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7 with range of 19\u0026ndash;70 years while in control group, the mean age was 44.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.4 with range of 19\u0026ndash;64. Among the patients in the study, 17 were males (56.7%) and 13 were females (43.3%) compared to 10 males (50%) and 10 females (50%) in control group. There was no significant difference between the two groups as regard age and sex \u003cb\u003e(p-value\u0026thinsp;=\u0026thinsp;0.531 \u0026amp; 0.643 respectively) (Table\u0026nbsp;1).\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eTable\u0026nbsp;(2)\u003c/b\u003e shows the description of clinical data in patient\u0026rsquo;s group. \u003cb\u003eAs regard duration\u003c/b\u003e, the mean disease duration of all studied patients was 13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2 years with minimum duration of 1 year and maximum duration of 40 years. \u003cb\u003eAs regard PASI score\u003c/b\u003e, the mean score of all studied patients was 17.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4 years with minimum score of 6 and maximum score of 41.7. There were 10 patients (33.3%) with moderate psoriasis, 9 patients (30%) with severe psoriasis and 11 patients (36.7%) with very severe disease.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTable\u0026nbsp;(3)\u003c/b\u003e shows a high statistically significant difference \u003cb\u003e(p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/b\u003e between studied groups as regard PDL1 expression in the dermis while no PD-L1 expression was observed in the keratinocytes in psoriatic skin and healthy controls. In patient\u0026rsquo;s group, there were 9 specimens (30%) of low expression and 21 specimens (70%) of high expression while in control group, there were 16 specimens (80%) of low expression and only 4 (20%) were with high expression \u003cb\u003e(Fig.\u0026nbsp;1, Fig.\u0026nbsp;2).\u003c/b\u003e Additionally, there was a high statistically significant \u003cb\u003e(p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/b\u003e increased number of positive cells in patient\u0026rsquo;s group (mean\u0026thinsp;=\u0026thinsp;24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.9, range\u0026thinsp;=\u0026thinsp;2\u0026ndash;70) when compared with control group (mean\u0026thinsp;=\u0026thinsp;6.05\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9, range\u0026thinsp;=\u0026thinsp;1\u0026ndash;18)\u003c/p\u003e\u003cp\u003e\u003cb\u003eTable\u0026nbsp;(4)\u003c/b\u003e shows statistically significant \u003cb\u003e(p-value\u0026thinsp;=\u0026thinsp;0.02)\u003c/b\u003e negative correlation \u003cb\u003e(r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.42)\u003c/b\u003e between PDL1 expression and duration of psoriasis \u003cb\u003e(Fig.\u0026nbsp;3).\u003c/b\u003e Moreover, there was high statistically significant \u003cb\u003e(p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/b\u003e negative correlation \u003cb\u003e(r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.77)\u003c/b\u003e between PDL1 expression and PASI score \u003cb\u003e(Fig.\u0026nbsp;4).\u003c/b\u003e While there was no statistically significant correlation \u003cb\u003e(p-value\u0026thinsp;=\u0026thinsp;0.081)\u003c/b\u003e between PDL1 expression and age.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePsoriasis is generally recognized as a Th1- and Th17-driven disease. In psoriasis vulgaris, cytokines from the Th1 axis (IL-12, IFN-γ, IL-12) and the Th17 pathway (IL-17F, IL-17A, IL-22, IL-21) recruit immune cells, resulting in continuous inflammation and keratinocyte proliferation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Both PD-1 and PD-L 1 are often expressed by T-cells, and Anti-PD-1 antibody therapy markedly modifies T-cell\u0026ndash;mediated adaptive immune responses, which is widely regarded as the primary mechanism underlying the onset or exacerbation of psoriasis associated with PD-1 blockade [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOnly a limited number of studies have examined PD-1 and PD-L1 expression in psoriatic lesional skin, and their findings have been inconsistent [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. So, the current study was conducted to investigate the expression of PD-L1 in psoriasis through its immunohistochemical (IHC) expression in involved skin in psoriatic cases.\u003c/p\u003e\u003cp\u003eThe present study showed a high statistically significant difference \u003cb\u003e(p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/b\u003e between studied groups as regard PDL1 expression in the dermis while no PD-L1 expression in the keratinocytes was observed in psoriatic skin and healthy controls. In patient\u0026rsquo;s group, there were 70% of patients with high expression and 30% with low expression while in control group, the majority of specimens (80%) of low expression and only 20% of high expression. Additionally, there was a high statistically significant \u003cb\u003e(p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/b\u003e increased number of positive cells in patient\u0026rsquo;s group when compared with control group; suggesting that disruption of the PD-1/PD-L1 axis may contribute to psoriasis pathogenesis. In the future, therapies targeting the PD-1/PD-L1 pathway could represent an emerging therapeutic option for psoriasis.\u003c/p\u003e\u003cp\u003eGiven that PD-1 is an immune system inhibitor co-receptor, it could seem illogical that autoimmune illnesses would lead to an increase in its expression. Nevertheless, study findings indicate that the PD-1/PD-L1 pathway is altered in chronic inflammatory diseases such as SLE and rheumatoid arthritis. Additionally, it has been suggested that PD-1 and/or its ligand dysfunction may play a significant role in the persistent hyperactivity of the T-cell-mediated immune response seen in a variety of autoimmune disorders such as psoriasis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGiven that T cell immunity plays a key role in the pathophysiology of psoriasis and that T cells frequently express PD-1 and PD-L1 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], this could explain a higher expression of PDL1 in psoriasis. Also, this may reflect an attempt at immune regulation to control T-cell activation.\u003c/p\u003e\u003cp\u003eThe discrepancy between dermal and epidermal PD-L1 expression suggested compartment-specific immune dysregulation in psoriasis. Since upregulation of PD-L1 in the dermis suggests an attempt at immune regulation in the dermis to control T-cell activation, absence of PD-L1 in the epidermis implies a failure of the epidermal compartment to engage immune checkpoints; contributing to persistent activation of T cells and chronic unregulated inflammatory characteristics.\u003c/p\u003e\u003cp\u003eOur results were in agreement with Emre et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] who demonstrated that PD-1 and PD-L1 expression in immune cells of dermal psoriatic skin was significantly higher compared with healthy controls, while neither psoriatic nor healthy keratinocytes showed PD-1 or PD-L1 expression. Furthermore, Kim et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] reported that, relative to normal skin and other inflammatory dermatoses such as pityriasis rosea, lichen planus, and allergic contact dermatitis, keratinocyte PD-L1 expression was markedly reduced in psoriatic epidermis. They proposed that the lack of PD-1 ligands may promote enhanced T-cell\u0026ndash;mediated inflammation and reduced Treg activity, both characteristic features of psoriasis, thereby highlighting the role of keratinocytes as central amplifiers and sustainers of psoriatic inflammation.\u003c/p\u003e\u003cp\u003eIn contrast tom our results, Du et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] observed in the majority of cases of oral lichen planus (OLP), PD-L1 and PD-L2 were both highly expressed on keratinocytes and weakly on the infiltrating T lymphocytes in the subepithelium. They proposed that the pathologically altered mucosal immunological milieu, which prevents T cell proliferation and rebalances local immune responses, may be the cause of the elevated expression of PD-L in OLP patients' mucosa.\u003c/p\u003e\u003cp\u003eAs regard the correlation study between PDL1 expression and other studied data in patients, there was a high statistically significant negative correlation between PDL1 expression and PASI score. Decreased PASI score in patients with high expression when compared with patients of low expression. This could be explained as PD-L1 as an Immunoregulatory Brake -via binding to PD-1 on T cells- resulting in inhibition of T-cell activation and suppressing immune responses. So, high PD-L1 expression might be a compensatory mechanism to dampen excessive inflammation. Therefore, when PD-L1 is more expressed, it may limit further immune-mediated damage, resulting in lower severity scores. Moreover, when PD-L1 expression is reduced or absent, this allows uncontrolled inflammation and more severe disease. While there was no statistically significant correlation between PDL1 expression and age in the present study.\u003c/p\u003e\u003cp\u003eIn addition, there was a statistically significant negative correlation between PDL1 expression and duration of psoriasis. This could be explained as psoriasis becomes more chronic, there may be progressive reduction in immune check point activity (reduced PD-L1 expression). This may be due to immune exhaustion or desensitization.\u003c/p\u003e\u003cp\u003eIn agreement to our results of correlation to PASI score, Emre et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] reported a significant negative correlation between PD-L1(+) immune cell counts and PASI scores, whereas no correlation was found with disease duration. The discrepancies among study findings may be attributed to the limited sample sizes or to variations in PD-1 and PD-L1 expression patterns between the epidermis and dermis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePD-L1 expression in immune cells within psoriatic skin is significantly elevated compared to that in healthy controls. It may play a key role in reducing the regulation of ineffective or harmful immune responses and maintaining immune tolerance. In the future, PD-1/PD-L1 pathway can be ideal treatment targets for psoriasis patients and medications modulating this pathway may be another promising option in therapy of psoriasis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFund: This work didn’t receive any fund from government or non-government institutions\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eِAzza Samy conceived and designed the study, recruited patients, and supervised the clinical work. May Mostafa contributed to patient evaluation, clinical data collection, and manuscript drafting. Ali Ayaad performed the histopathological examination, conducted and scored the PD-L1 immunohistochemistry. Shaimaa Elgohary validated the immunohistochemical results, contributed to data analysis, and prepared pathology figures. All authors interpreted the data, revised the manuscript critically for important intellectual content, and approved the final version for submission.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003ethe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBrezinski EA, Dhillon JS, Armstrong AW (2015) Economic burden of psoriasis in the United States: A systematic review. JAMA Dermatol 151:651\u0026ndash;658. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jamadermatol.2014.3593\u003c/span\u003e\u003cspan address=\"10.1001/jamadermatol.2014.3593\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMateu-Arrom L, Puig L (2023) Genetic and epigenetic mechanisms of psoriasis. Genes 14:1619. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/genes14081619\u003c/span\u003e\u003cspan address=\"10.3390/genes14081619\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuzuki T, Ito T, Gilhar A, Bertolini M, Paus R (2022) The hair follicle-psoriasis axis: Shared regulatory mechanisms and therapeutic targets. Exp Dermatol 31:266\u0026ndash;279. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/exd.14535\u003c/span\u003e\u003cspan address=\"10.1111/exd.14535\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDeng Y, Chang C, Lu Q (2016) The inflammatory response in psoriasis: A comprehensive review. Clin Rev Allergy Immunol 50:377\u0026ndash;389. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12016-016-8535-x\u003c/span\u003e\u003cspan address=\"10.1007/s12016-016-8535-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEmre S, S\u0026uuml;ng\u0026uuml; N, Hayran Y, Dursun R, Aşkın \u0026Ouml;, Ergun T (2023) Investigation of the PD-1/PD-L1 expression in the lesional skins of patients with psoriasis. Dermatol Pract Concept 13:e2023134. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5826/dpc.1302a134\u003c/span\u003e\u003cspan address=\"10.5826/dpc.1302a134\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, Rosenberg SA (2009) Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114:1537\u0026ndash;1544. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/blood-2008-12-195792\u003c/span\u003e\u003cspan address=\"10.1182/blood-2008-12-195792\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLin X, Kang K, Chen P, Liu W, Mo Y, Zeng H, Zhang Y (2024) Regulatory mechanisms of PD-1/PD-L1 in cancers. Mol Cancer 23:108. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12943-024-01973-5\u003c/span\u003e\u003cspan address=\"10.1186/s12943-024-01973-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiang SC, Latchman YE, Buhlmann JE, Tomczak MF, Horwitz BH, Freeman GJ, Sharpe AH (2003) Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol 33:2706\u0026ndash;2716. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/eji.200324228\u003c/span\u003e\u003cspan address=\"10.1002/eji.200324228\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFreeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027\u0026ndash;1034. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1084/jem.192.7.1027\u003c/span\u003e\u003cspan address=\"10.1084/jem.192.7.1027\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZamani RM, Aslani S, Salmaninejad A, Javan MR, Rezaei R (2016) PD-1/PD-L and autoimmunity: A growing relationship. Cell Immunol 310:27\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.cellimm.2016.09.004\u003c/span\u003e\u003cspan address=\"10.1016/j.cellimm.2016.09.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWan Z, Huang J, Ou X, Wang M, Li X, Deng H, Lu T (2024) Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. Bras Dermatol 99:425\u0026ndash;432. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.abd.2023.02.010\u003c/span\u003e\u003cspan address=\"10.1016/j.abd.2023.02.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStrober B, Karki C, Mason M, Guo Y, Alemao E, Pillai R, Reich K (2017) Impact of Psoriasis Area and Severity Index (PASI) on patient-reported outcomes in patients with psoriasis: Results from the Corrona Psoriasis Registry. J Am Acad Dermatol 76:AB406. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jaad.2016.12.155\u003c/span\u003e\u003cspan address=\"10.1016/j.jaad.2016.12.155\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChong HT, Kopecki Z, Cowin AJ (2013) Lifting the silver flakes: The pathogenesis and management of chronic plaque psoriasis. Biomed Res Int 2013:168321. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2013/168321\u003c/span\u003e\u003cspan address=\"10.1155/2013/168321\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAdamczyk M, Krasowska D (2021) PD-1/PD-L1 pathway in psoriasis and psoriatic arthritis: A review. Adv Dermatol Allergol 38:925\u0026ndash;930. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5114/ada.2020.98239\u003c/span\u003e\u003cspan address=\"10.5114/ada.2020.98239\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim DS, Je JH, Kim SH, Seo YJ, Kim CD, Lee JH (2015) Programmed death-ligand 1, 2 expressions are decreased in the psoriatic epidermis. Arch Dermatol Res 307:531\u0026ndash;538. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00403-015-1559-3\u003c/span\u003e\u003cspan address=\"10.1007/s00403-015-1559-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDu GH, Qin XP, Li Q, Sun YX, Zhang ZY (2011) The high expression level of programmed death-1 ligand 2 in oral lichen planus and the possible costimulatory effect on human T cells. J Oral Pathol Med 40:525\u0026ndash;532. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1600-0714.2011.01025.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1600-0714.2011.01025.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable (1): Comparison between studied groups regarding age and sex.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"657\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N = 30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N = 20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eStat. test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\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 rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e \u003cstrong\u003e(years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e47.3 \u0026plusmn; 13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e44.8 \u0026plusmn; 13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eT = 0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0.531 NS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e19 - 70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e19 \u0026ndash; 64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e56.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e = 0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0.643 NS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eT: independent sample T test.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;X\u003csup\u003e2\u003c/sup\u003e: Chi-square test.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNS: p-value \u0026gt; 0.05 is considered non-significant.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (2): Description of clinical data in patient\u0026rsquo;s group.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"662\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient\u0026rsquo;s group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N = 30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration\u003c/strong\u003e \u003cstrong\u003e(years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e13.9 \u0026plusmn; 10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMin - Max\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e1 \u0026ndash; 40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePASI score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e17.9 \u0026plusmn; 8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMin - Max\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e6 \u0026ndash; 41.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003ePASI score categories\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e33.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSevere\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e30%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVery severe\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNo: number, SD: Standard deviation, PASI: Psoriasis Area and Severity Index\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3): Comparison of PDL1 expression and Number of positive cells between studied groups.\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"574\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N = 30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N = 20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eStat. test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\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 rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo of positive cells\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e24.5 \u0026plusmn; 16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e6.05 \u0026plusmn; 4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eT = 4.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001 HS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e2 - 70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e1 \u0026ndash; 18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePDL1 expression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e30%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003csup\u003e2\u003c/sup\u003e = 12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001 HS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eT: independent sample T test.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;HS: p-value \u0026lt; 0.001 is considered highly significant.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eX\u003csup\u003e2\u003c/sup\u003e: Chi-square test.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (4):\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCorrelation study between\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePDL1 expression and other studied data in patient\u0026rsquo;s group\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"685\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePDL1 expression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePearson correlation coefficient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\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\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDuration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.02 *\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePASI score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.77\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001 **\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;(r): Pearson correlation coefficient.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e*: p-value \u0026lt; 0.05 is considered significant.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e**: p-value \u0026lt; 0.001 is considered highly significant. \u0026nbsp; \u0026nbsp; \u0026nbsp;NS: p-value \u0026gt; 0.05 is considered non-significant.\u003c/strong\u003e\u003c/p\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":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Psoriasis, Immunohistochemistry, PD-L1, Immunotherapy","lastPublishedDoi":"10.21203/rs.3.rs-7435479/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7435479/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePsoriasis is a chronic, immune-mediated inflammatory disorder in which persistent T-cell activation by antigen-presenting cells (APCs) and defects in immune tolerance contribute to disease development, similar to other autoimmune conditions. Programmed death-1 (PD-1) is an inhibitory co-receptor that regulates inflammation and supports peripheral immune tolerance. Dysfunction of the PD-1/PD-L1 pathway is thought to play a significant role in the pathogenesis of various immune-mediated diseases. The objective of this study was to investigate the expression of Programmed death-ligand 1 (PD-L1) in psoriasis through its immunohistochemical (IHC) expression in involved skin in psoriatic cases. This prospective case control study was conducted on 30 skin biopsies of patients with plaque psoriasis and 20 biopsies of sex and age matched individuals as control group. Immunohistochemical staining using monoclonal mouse antibody against PDL-1(22C3) was applied on skin biopsy specimens obtained from both patient and control groups. There was a high statistically significant difference \u003cb\u003e(p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/b\u003e between both groups as regard PDL1 expression. In patient\u0026rsquo;s group, 30% of specimens were with low expression and 70% of specimens with high expression (80% low expression \u0026amp; 20% high expression in control group). A statistically significant and strong inverse correlation was observed between the number of PD-L1(+) immune cells and PASI scores \u003cb\u003e(P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.77).\u003c/b\u003e Furthermore, the number of PD-L1(+) immune cells demonstrated a statistically significant negative correlation with disease duration \u003cb\u003e(P\u0026thinsp;=\u0026thinsp;0.02, r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.42).\u003c/b\u003e In conclusion, PD-L1 expression in immune cells was significantly higher compared to healthy controls, indicating a potential role of PD-L1 in the disease pathogenesis.\u003c/p\u003e","manuscriptTitle":"Immunohistochemical Expression of Programmed death-ligand 1 (PD-L1) in Lesional Psoriatic Skin: A Study of Its Role in Psoriasis Pathogenesis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 05:38:57","doi":"10.21203/rs.3.rs-7435479/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-23T19:08:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-20T16:36:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-09T11:12:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"101369038709026152616782566737865053254","date":"2025-11-03T14:49:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39767845508618433784045092401000236024","date":"2025-10-30T13:57:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-28T19:57:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-25T12:05:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-25T12:05:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2025-08-22T14:35:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"79210b06-ccb0-41d9-a798-2df8342cd352","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T20:08:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-10 05:38:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7435479","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7435479","identity":"rs-7435479","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}