The prevalence of alpha-gal IgE among patients with confirmed Lyme serology result

The prevalence of alpha-gal IgE among patients with confirmed Lyme serology result | 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 The prevalence of alpha-gal IgE among patients with confirmed Lyme serology result Kamran Kadkhoda, Alison Schwaben, Matthew Dee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9021387/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Given the significant rise in the incidence of alpha-gal syndrome alongside the geographical expansion of ticks in recent years, it is crucial to conduct studies aimed at raising awareness—particularly among patients with a history of, or current diagnosis of, Lyme disease, to improve their quality of life. Our study is unique in addressing this important intersection. Two groups composed of 200 residuals de-identified samples originally collected during the peak of tick activity season in Northeast Ohio were tested for alpha-gal IgE. The first group (n = 100) was from patients with Lyme IgG western blot positive results, and the remainder were from healthy subjects only tested for immune status. Of the 200 samples, 17 tested positive for α-Gal IgE: 15 from the Lyme-positive group and 2 from the control group. A Fisher Exact Test showed strong statistical significance between the two groups ( P = 0.0015). Although alpha-gal syndrome had been previously associated with a history of American lone start tick bite, this study (given its controlled design) for the first time in North America shows a strong association between α-Gal IgE positivity and exposure to Ixodes ticks. This is of paramount importance given the vast prevalence of Ixodes ticks especially in areas where the American lone start ticks are scarce. Alpha-gal tick Lyme Ixodes Introduction Allergy to red meat—including beef, pork, and mutton—has risen substantially in the United States since 2010 and is becoming a public health concern ( 1 ). This condition is primarily driven by an epitope found in red meat from non-primate mammals, known as galactose-α-1,3-galactose (α-Gal). While α-Gal is not expressed on human tissues, it is present in certain bacteria within the normal gastrointestinal flora, as well as in microorganisms such as Borrelia burgdorferi , the causative agent of Lyme disease ( 2 ). Sensitization to α-Gal, which may lead to α-Gal allergy (also known as α-Gal syndrome), appears to require a tick bite. This phenomenon has been most associated with the Lone Star tick ( Amblyomma americanum ) ( 2 ). However, recent allergonomics research has demonstrated the presence of α-Gal in the gut and saliva of ticks in the Ixodes ricinus complex, including Ixodes scapularis , the most common Lyme disease vector in the United States ( 3 ). Sensitization typically occurs when heavily α-Gal-glycosylated proteins such as vitellogenin and α-2 macroglobulin are introduced into the host's skin via tick bite. In this case, α-Gal acts as a hapten, with the attached protein serving as a carrier that triggers an immune response ( 4 ). Additionally, tick saliva is known to skew the immune response toward a Th2 profile, facilitating class switching to IgE against α-Gal ( 5 ). The Lone Star tick is primarily found in the eastern, southeastern, and midwestern United States, while Ixodes (blacklegged) ticks have a wider distribution, spanning the eastern U.S., Midwest, and parts of the Pacific region ( 6 ). In Ohio, Ixodes ticks are found throughout the state, including Northeast Ohio, whereas Lone Star ticks are typically limited to the southern half of the state ( 7 ). Methods We aimed to investigate the prevalence of α-Gal sensitization among patients with confirmed positive Lyme serology residing in Northeast Ohio. We selected a sample of 100 consecutive sera submitted to our laboratory for routine Lyme serodiagnosis. Only sera with a positive Lyme IgG Western blot, interpreted per CDC criteria, were included. A control group of 100 sera submitted for occupational immune status determination (with no concurrent Lyme serology orders) was used. All specimens were originally collected during the peak Ixodes ticks activity season in Northeast Ohio (June through August 2025). Age and sex were documented; samples were then de-identified and frozen for up to 14 days prior to α-Gal IgE testing. Both groups were balanced for sex (50% male and female). The overall age range was 21–87 years, with a median of 55 years. Median ages for females and males were 53.5 and 56 years, respectively. In the Lyme-positive group, the age range was 21–87 years (median 60.5), and in the control group, 30–68 years (median 49). The control group did have any past or concurrent Lyme testing requests suggesting no known risk factors for tick exposure. Samples were tested for α-Gal IgE using the ImmunoCAP™ instrument (Thermo Fisher Scientific), per the manufacturer’s instructions, with a positivity cutoff of 0.1 kU/L—a test routinely offered in our laboratory. Results Of the 200 samples, 17 tested positive for α-Gal IgE: 15 from the Lyme-positive group and 2 from the control group. The overall α-Gal IgE range was 0.1–23.1 kU/L, with a mean of 2.59, median of 0.38, and interquartile range (IQR) of 1.15 kU/L. For the Lyme-positive group, the range was 0.1–23.1 kU/L (mean 2.91, median 0.48, IQR 1.59). In the control group, the range was 0.11–0.18 kU/L (mean and median 0.14 kU/L), with IQR not calculable due to only two positive cases. A Fisher Exact Test (GraphPad) showed strong statistical significance between the two groups ( P = 0.0015). However, linear regression analysis (GraphPad) did not demonstrate a significant correlation between age and α-Gal IgE levels ( P = 0.76). Using an enhanced cutoff of 0.35 kU/L which is commonly used for allergens still showed 7 with such results in the Lyme positive group as opposed to none in the control group. Discussion Two confirmed cases of α-Gal syndrome following Ixodes tick bites were reported earlier this year ( 8 , 9 ). These patients—aged 45 and 61—are close in age to the median of our Lyme-positive group. In the first case, symptoms of α-Gal syndrome began nine days after the tick bite, which raises questions about the rapidity of IgE development. It is more plausible that this patient had prior exposure and was already sensitized, which was supported by her initially high α-Gal IgE levels that later declined. The second case experienced severe symptoms, 32 days post-bite, with an initial α-Gal IgE level of 27.4 kU/L that declined to 6.91 kU/L within six months and to 0.72 kU/L three years later. Following another Ixodes tick bite, her α-Gal IgE spiked to 20.2 kU/L within four weeks. A similar episode occurred two years later, demonstrating a decline followed by an anamnestic rise in α-Gal IgE levels post-bite. These findings are relevant to our study. We observed α-Gal IgE levels as low as 0.1 kU/L. This could suggest a) these patients were newly exposed to Ixodes ticks, leading to concurrent Lyme disease and α-Gal sensitization, or b) they had prior exposures, and their IgE levels had since declined—possibly due to the short half-life of circulating IgE and its binding to mast cells. This could explain the lack of correlation between age and α-Gal IgE levels in our cohort. As a limitation of our study, we did not have access to patients’ data to correlate their results with the clinical picture. Mere α-Gal IgE positivity does not necessarily denote α-Gal syndrome but rather proves sensitization. Multicenter, prospective studies with long-term follow-up are needed to further explore and validate these findings. Declarations Conflicts of interest : None declared. Authors have read the manuscript and consented to publication. Contribution : KK, design, budget and IRB, data analysis, manuscript write up; AS, sample collection and testing, manuscript review; MD, operational support, manuscript review. Ethics . The study was approved by the Cleveland Clinic Foundation Institutional Review Board (IRB decision reference #25-811). Informed consent was exempted by the aforementioned IRB as the specimens were originally submitted for standard of care testing and the residual samples were de-identified. Clinical trial number : not applicable. Funding . This study was funded by the Cleveland Clinic Foundation Pathology and Laboratory Medicine Department research funds. No AI-assisted technology was used for manuscript preparation or data analysis. Data availability . The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author [KK] upon request. References Thompson JM, Carpenter A, Kersh GJ, Wachs T, Commins SP, Salzer JS. Geographic Distribution of Suspected Alpha-gal Syndrome Cases - United States, January 2017-December 2022. MMWR Morb Mortal Wkly Rep. 2023;72(30):815–20. Román-Carrasco P, Hemmer W, Cabezas-Cruz A, Hodžić A, de la Fuente J, Swoboda I. The α-Gal Syndrome and Potential Mechanisms. Front Allergy. 2021;2:783279. Cabezas-Cruz A, Hodžić A, Román-Carrasco P, Mateos-Hernández L, Duscher GG, Sinha DK, et al. Environmental and Molecular Drivers of the α-Gal Syndrome. Front Immunol. 2019;10:1210. Apostolovic D, Mihailovic J, Commins SP, Wijnveld M, Kazimirova M, Starkhammar M, et al. Allergenomics of the tick Ixodes ricinus reveals important α-Gal-carrying IgE-binding proteins in red meat allergy. Allergy. 2020;75(1):217–20. Alarcon-Chaidez FJ, Boppana VD, Hagymasi AT, Adler AJ, Wikel SK. A novel sphingomyelinase-like enzyme in Ixodes scapularis tick saliva drives host CD4 T cells to express IL-4. Parasite Immunol. 2009;31(4):210–9. Where ticks live CDC: CDC. 2025 [updated 7/30/2025. Available from: https://www.cdc.gov/ticks/about/where-ticks-live.html Tick in Ohio: Ohio Department of Health. 2025 [Available from: https://odh.ohio.gov/know-our-programs/zoonotic-disease-program/animals/ticks-in-ohio Butler WK, Oltean HN, Dykstra EA, Saunders E, Salzer JS, Commins SP. Onset of Alpha-Gal Syndrome after Tick Bite, Washington, USA. Emerg Infect Dis. 2025;31(4):829–32. Saunders EF, Sohail H, Myles DJ, Charnetzky D, Ayres BN, Nicholson WL, et al. Alpha-Gal Syndrome after Ixodes scapularis Tick Bite and Statewide Surveillance, Maine, USA, 2014–2023. Emerg Infect Dis. 2025;31(4):809–13. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-9021387","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":603271361,"identity":"2adf499a-5848-488d-8591-60d341656fff","order_by":0,"name":"Kamran Kadkhoda","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuUlEQVRIie3PMQrCMACF4Ve6pnRNKdQrVHIhJdAuKQhdOqg4taNrjiF0dYgEdCl4hU6dHPQGVnFxSrMJ5t8/Hg9wuX4wCjAfWCSA19sRBvipHVnuJpOo0S1bVVm+bzTwOG7MJCZZyWUnCtlxeHK4mEkCwXRQV8WBhson6jyBhLc3yVPqYxqJqWA8qMXiQ9ZmEsmhZKTL5q8vJ6mUmdArb2NS8VnYaK+/q62ZfDVOaEsyZrvicrlc/9ATr6o1tCg9spUAAAAASUVORK5CYII=","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":true,"prefix":"","firstName":"Kamran","middleName":"","lastName":"Kadkhoda","suffix":""},{"id":603271366,"identity":"a51450b5-5a37-490a-9bb1-9377deda685d","order_by":1,"name":"Alison Schwaben","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Alison","middleName":"","lastName":"Schwaben","suffix":""},{"id":603271373,"identity":"f8f308e7-88e6-4cd3-a58b-30cbe4f93b6f","order_by":2,"name":"Matthew Dee","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Dee","suffix":""}],"badges":[],"createdAt":"2026-03-03 14:38:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9021387/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9021387/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107136906,"identity":"8551d904-e81b-4a8c-b231-01a624ea8579","added_by":"auto","created_at":"2026-04-17 08:13:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":120504,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9021387/v1/5d04fbd2-ff0d-4d0b-a9ff-f71d1b896880.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The prevalence of alpha-gal IgE among patients with confirmed Lyme serology result","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAllergy to red meat\u0026mdash;including beef, pork, and mutton\u0026mdash;has risen substantially in the United States since 2010 and is becoming a public health concern (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). This condition is primarily driven by an epitope found in red meat from non-primate mammals, known as galactose-α-1,3-galactose (α-Gal). While α-Gal is not expressed on human tissues, it is present in certain bacteria within the normal gastrointestinal flora, as well as in microorganisms such as \u003cem\u003eBorrelia burgdorferi\u003c/em\u003e, the causative agent of Lyme disease (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSensitization to α-Gal, which may lead to α-Gal allergy (also known as α-Gal syndrome), appears to require a tick bite. This phenomenon has been most associated with the Lone Star tick (\u003cem\u003eAmblyomma americanum\u003c/em\u003e) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, recent allergonomics research has demonstrated the presence of α-Gal in the gut and saliva of ticks in the \u003cem\u003eIxodes ricinus\u003c/em\u003e complex, including \u003cem\u003eIxodes scapularis\u003c/em\u003e, the most common Lyme disease vector in the United States (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Sensitization typically occurs when heavily α-Gal-glycosylated proteins such as vitellogenin and α-2 macroglobulin are introduced into the host's skin via tick bite. In this case, α-Gal acts as a hapten, with the attached protein serving as a carrier that triggers an immune response (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Additionally, tick saliva is known to skew the immune response toward a Th2 profile, facilitating class switching to IgE against α-Gal (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe Lone Star tick is primarily found in the eastern, southeastern, and midwestern United States, while \u003cem\u003eIxodes\u003c/em\u003e (blacklegged) ticks have a wider distribution, spanning the eastern U.S., Midwest, and parts of the Pacific region (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In Ohio, \u003cem\u003eIxodes\u003c/em\u003e ticks are found throughout the state, including Northeast Ohio, whereas Lone Star ticks are typically limited to the southern half of the state (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe aimed to investigate the prevalence of α-Gal sensitization among patients with confirmed positive Lyme serology residing in Northeast Ohio. We selected a sample of 100 consecutive sera submitted to our laboratory for routine Lyme serodiagnosis. Only sera with a positive Lyme IgG Western blot, interpreted per CDC criteria, were included. A control group of 100 sera submitted for occupational immune status determination (with no concurrent Lyme serology orders) was used. All specimens were originally collected during the peak \u003cem\u003eIxodes\u003c/em\u003e ticks activity season in Northeast Ohio (June through August 2025). Age and sex were documented; samples were then de-identified and frozen for up to 14 days prior to α-Gal IgE testing. Both groups were balanced for sex (50% male and female). The overall age range was 21\u0026ndash;87 years, with a median of 55 years. Median ages for females and males were 53.5 and 56 years, respectively. In the Lyme-positive group, the age range was 21\u0026ndash;87 years (median 60.5), and in the control group, 30\u0026ndash;68 years (median 49). The control group did have any past or concurrent Lyme testing requests suggesting no known risk factors for tick exposure.\u003c/p\u003e \u003cp\u003eSamples were tested for α-Gal IgE using the ImmunoCAP\u0026trade; instrument (Thermo Fisher Scientific), per the manufacturer\u0026rsquo;s instructions, with a positivity cutoff of 0.1 kU/L\u0026mdash;a test routinely offered in our laboratory.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOf the 200 samples, 17 tested positive for α-Gal IgE: 15 from the Lyme-positive group and 2 from the control group. The overall α-Gal IgE range was 0.1\u0026ndash;23.1 kU/L, with a mean of 2.59, median of 0.38, and interquartile range (IQR) of 1.15 kU/L. For the Lyme-positive group, the range was 0.1\u0026ndash;23.1 kU/L (mean 2.91, median 0.48, IQR 1.59). In the control group, the range was 0.11\u0026ndash;0.18 kU/L (mean and median 0.14 kU/L), with IQR not calculable due to only two positive cases. A Fisher Exact Test (GraphPad) showed strong statistical significance between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0015). However, linear regression analysis (GraphPad) did not demonstrate a significant correlation between age and α-Gal IgE levels (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.76). Using an enhanced cutoff of 0.35 kU/L which is commonly used for allergens still showed 7 with such results in the Lyme positive group as opposed to none in the control group.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTwo confirmed cases of α-Gal syndrome following \u003cem\u003eIxodes\u003c/em\u003e tick bites were reported earlier this year (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). These patients\u0026mdash;aged 45 and 61\u0026mdash;are close in age to the median of our Lyme-positive group. In the first case, symptoms of α-Gal syndrome began nine days after the tick bite, which raises questions about the rapidity of IgE development. It is more plausible that this patient had prior exposure and was already sensitized, which was supported by her initially high α-Gal IgE levels that later declined. The second case experienced severe symptoms, 32 days post-bite, with an initial α-Gal IgE level of 27.4 kU/L that declined to 6.91 kU/L within six months and to 0.72 kU/L three years later. Following another \u003cem\u003eIxodes\u003c/em\u003e tick bite, her α-Gal IgE spiked to 20.2 kU/L within four weeks. A similar episode occurred two years later, demonstrating a decline followed by an anamnestic rise in α-Gal IgE levels post-bite.\u003c/p\u003e \u003cp\u003eThese findings are relevant to our study. We observed α-Gal IgE levels as low as 0.1 kU/L. This could suggest \u003cem\u003ea)\u003c/em\u003e these patients were newly exposed to \u003cem\u003eIxodes\u003c/em\u003e ticks, leading to concurrent Lyme disease and α-Gal sensitization, or \u003cem\u003eb)\u003c/em\u003e they had prior exposures, and their IgE levels had since declined\u0026mdash;possibly due to the short half-life of circulating IgE and its binding to mast cells. This could explain the lack of correlation between age and α-Gal IgE levels in our cohort.\u003c/p\u003e \u003cp\u003eAs a limitation of our study, we did not have access to patients\u0026rsquo; data to correlate their results with the clinical picture. Mere α-Gal IgE positivity does not necessarily denote α-Gal syndrome but rather proves sensitization. Multicenter, prospective studies with long-term follow-up are needed to further explore and validate these findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e: None declared. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthors have read the manuscript and consented to publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContribution\u003c/strong\u003e: KK, design, budget and IRB, data analysis, manuscript write up; AS, sample collection and testing, manuscript review; MD, operational support, manuscript review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics\u003c/strong\u003e. The study was approved by the Cleveland Clinic Foundation Institutional Review Board (IRB decision reference #25-811). Informed consent was exempted by the aforementioned IRB as the specimens were originally submitted for standard of care testing and the residual samples were de-identified.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e. This study was funded by the Cleveland Clinic Foundation Pathology and Laboratory Medicine Department research funds. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo AI-assisted technology was used for manuscript preparation or data analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e. The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author [KK] upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eThompson JM, Carpenter A, Kersh GJ, Wachs T, Commins SP, Salzer JS. Geographic Distribution of Suspected Alpha-gal Syndrome Cases - United States, January 2017-December 2022. MMWR Morb Mortal Wkly Rep. 2023;72(30):815\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRom\u0026aacute;n-Carrasco P, Hemmer W, Cabezas-Cruz A, Hodžić A, de la Fuente J, Swoboda I. The α-Gal Syndrome and Potential Mechanisms. Front Allergy. 2021;2:783279.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCabezas-Cruz A, Hodžić A, Rom\u0026aacute;n-Carrasco P, Mateos-Hern\u0026aacute;ndez L, Duscher GG, Sinha DK, et al. Environmental and Molecular Drivers of the α-Gal Syndrome. Front Immunol. 2019;10:1210.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eApostolovic D, Mihailovic J, Commins SP, Wijnveld M, Kazimirova M, Starkhammar M, et al. Allergenomics of the tick Ixodes ricinus reveals important α-Gal-carrying IgE-binding proteins in red meat allergy. Allergy. 2020;75(1):217\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlarcon-Chaidez FJ, Boppana VD, Hagymasi AT, Adler AJ, Wikel SK. A novel sphingomyelinase-like enzyme in Ixodes scapularis tick saliva drives host CD4 T cells to express IL-4. Parasite Immunol. 2009;31(4):210\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhere ticks live CDC: CDC. 2025 [updated 7/30/2025. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/ticks/about/where-ticks-live.html\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/ticks/about/where-ticks-live.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTick in Ohio: Ohio Department of Health. 2025 [Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://odh.ohio.gov/know-our-programs/zoonotic-disease-program/animals/ticks-in-ohio\u003c/span\u003e\u003cspan address=\"https://odh.ohio.gov/know-our-programs/zoonotic-disease-program/animals/ticks-in-ohio\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eButler WK, Oltean HN, Dykstra EA, Saunders E, Salzer JS, Commins SP. Onset of Alpha-Gal Syndrome after Tick Bite, Washington, USA. Emerg Infect Dis. 2025;31(4):829\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaunders EF, Sohail H, Myles DJ, Charnetzky D, Ayres BN, Nicholson WL, et al. Alpha-Gal Syndrome after Ixodes scapularis Tick Bite and Statewide Surveillance, Maine, USA, 2014\u0026ndash;2023. Emerg Infect Dis. 2025;31(4):809\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Alpha-gal, tick, Lyme, Ixodes","lastPublishedDoi":"10.21203/rs.3.rs-9021387/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9021387/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eGiven the significant rise in the incidence of alpha-gal syndrome alongside the geographical expansion of ticks in recent years, it is crucial to conduct studies aimed at raising awareness\u0026mdash;particularly among patients with a history of, or current diagnosis of, Lyme disease, to improve their quality of life. Our study is unique in addressing this important intersection. Two groups composed of 200 residuals de-identified samples originally collected during the peak of tick activity season in Northeast Ohio were tested for alpha-gal IgE. The first group (n\u0026thinsp;=\u0026thinsp;100) was from patients with Lyme IgG western blot positive results, and the remainder were from healthy subjects only tested for immune status. Of the 200 samples, 17 tested positive for α-Gal IgE: 15 from the Lyme-positive group and 2 from the control group. A Fisher Exact Test showed strong statistical significance between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0015). Although alpha-gal syndrome had been previously associated with a history of American lone start tick bite, this study (given its controlled design) for the first time in North America shows a strong association between α-Gal IgE positivity and exposure to \u003cem\u003eIxodes\u003c/em\u003e ticks. This is of paramount importance given the vast prevalence of \u003cem\u003eIxodes\u003c/em\u003e ticks especially in areas where the American lone start ticks are scarce.\u003c/p\u003e","manuscriptTitle":"The prevalence of alpha-gal IgE among patients with confirmed Lyme serology result","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-11 09:25:19","doi":"10.21203/rs.3.rs-9021387/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d68e0b6f-b01a-45f6-b417-6f22bba9f246","owner":[],"postedDate":"March 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-17T08:11:14+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-11 09:25:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9021387","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9021387","identity":"rs-9021387","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}