A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 era

IntroductionVaccinations have had a transformative impact on public health, reducing the incidence of many infectious diseases and increasing survival. However, there remains uncertainty about the potential of vaccines to trigger autoimmune diseases such as the idiopathic inflammatory myopathies (II...

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Main Authors: Eaman Alhassan, Anna Patnaik, Ejaz A. Shamim, Janardan P. Pandey, Lisa G. Rider, Frederick W. Miller
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1539659/full
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author Eaman Alhassan
Anna Patnaik
Anna Patnaik
Ejaz A. Shamim
Ejaz A. Shamim
Ejaz A. Shamim
Janardan P. Pandey
Lisa G. Rider
Frederick W. Miller
Frederick W. Miller
author_facet Eaman Alhassan
Anna Patnaik
Anna Patnaik
Ejaz A. Shamim
Ejaz A. Shamim
Ejaz A. Shamim
Janardan P. Pandey
Lisa G. Rider
Frederick W. Miller
Frederick W. Miller
author_sort Eaman Alhassan
collection DOAJ
description IntroductionVaccinations have had a transformative impact on public health, reducing the incidence of many infectious diseases and increasing survival. However, there remains uncertainty about the potential of vaccines to trigger autoimmune diseases such as the idiopathic inflammatory myopathies (IIM). Myositis after vaccination (MAV) is a rare clinical entity, but given immunogenetic associations with other adverse events, we explored genetic risk factors, particularly human leukocyte antigen (HLA) alleles and GM/KM immunoglobulin allotypes, that may predispose individuals to develop MAV.MethodsWe examined clinical characteristics, vaccination history, autoantibodies, HLA alleles and GM/KM allotypes from 56 patients who developed MAV, 133 myositis cases with no documented vaccination within 6 months of onset (non-MAV), and 527 healthy controls from the pre-COVID-19 era. Genotyping for HLA and GM/KM allotypes was performed by standard assays. Differences in allele frequencies in race-matched groups were evaluated using chi-square tests, odds ratios (OR) and 95% confidence intervals (CI). Multivariate logistic regression adjusted for age, sex, and vaccination type. Statistical significance was defined as a Holms corrected p-value of less than 0.05.ResultsNo clinical or serologic differences were found between MAV and non-MAV patients. However, the HLA-DQA1*03:03 allele was a unique risk factor for MAV in Caucasians (OR=3.87, 95% CI=1.56-9.54, p=0.002), while the known myositis risk factor, HLA-DRB1*03:01, was a protective factor for MAV (OR=0.41, 95% CI=0,18-0.94, p= 0.033). GM2, GM13, and KM1 allotypes were more frequently observed in MAV patients than healthy controls, and other HLA alleles were risk or protective factors for specific vaccines given in patients who developed MAV.ConclusionImmunogenetic factors may influence the likelihood of developing MAV. Further studies of larger, deeply phenotyped populations are needed to confirm these associations and could inform personalized risk assessments and targeted interventions, thereby enhancing vaccine safety.
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spelling doaj-art-6a77d36f9f6f449e8db2d24f51a0423c2025-08-20T03:36:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.15396591539659A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 eraEaman Alhassan0Anna Patnaik1Anna Patnaik2Ejaz A. Shamim3Ejaz A. Shamim4Ejaz A. Shamim5Janardan P. Pandey6Lisa G. Rider7Frederick W. Miller8Frederick W. Miller9Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United StatesDepartment of Neurology, Johns Hopkins University, Baltimore, MD, United StatesEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, United StatesEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, United StatesMid-Atlantic Permanente Medical Group and Mid-Atlantic Permanente Research Institute, Washington DC, United StatesNational Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, MD, United StatesDepartment of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC, United StatesEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, United StatesEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, United StatesEnvironmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United StatesIntroductionVaccinations have had a transformative impact on public health, reducing the incidence of many infectious diseases and increasing survival. However, there remains uncertainty about the potential of vaccines to trigger autoimmune diseases such as the idiopathic inflammatory myopathies (IIM). Myositis after vaccination (MAV) is a rare clinical entity, but given immunogenetic associations with other adverse events, we explored genetic risk factors, particularly human leukocyte antigen (HLA) alleles and GM/KM immunoglobulin allotypes, that may predispose individuals to develop MAV.MethodsWe examined clinical characteristics, vaccination history, autoantibodies, HLA alleles and GM/KM allotypes from 56 patients who developed MAV, 133 myositis cases with no documented vaccination within 6 months of onset (non-MAV), and 527 healthy controls from the pre-COVID-19 era. Genotyping for HLA and GM/KM allotypes was performed by standard assays. Differences in allele frequencies in race-matched groups were evaluated using chi-square tests, odds ratios (OR) and 95% confidence intervals (CI). Multivariate logistic regression adjusted for age, sex, and vaccination type. Statistical significance was defined as a Holms corrected p-value of less than 0.05.ResultsNo clinical or serologic differences were found between MAV and non-MAV patients. However, the HLA-DQA1*03:03 allele was a unique risk factor for MAV in Caucasians (OR=3.87, 95% CI=1.56-9.54, p=0.002), while the known myositis risk factor, HLA-DRB1*03:01, was a protective factor for MAV (OR=0.41, 95% CI=0,18-0.94, p= 0.033). GM2, GM13, and KM1 allotypes were more frequently observed in MAV patients than healthy controls, and other HLA alleles were risk or protective factors for specific vaccines given in patients who developed MAV.ConclusionImmunogenetic factors may influence the likelihood of developing MAV. Further studies of larger, deeply phenotyped populations are needed to confirm these associations and could inform personalized risk assessments and targeted interventions, thereby enhancing vaccine safety.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1539659/fullpolymyositisdermatomyositisvaccinationadverse eventsHLAGM/KM
spellingShingle Eaman Alhassan
Anna Patnaik
Anna Patnaik
Ejaz A. Shamim
Ejaz A. Shamim
Ejaz A. Shamim
Janardan P. Pandey
Lisa G. Rider
Frederick W. Miller
Frederick W. Miller
A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 era
Frontiers in Immunology
polymyositis
dermatomyositis
vaccination
adverse events
HLA
GM/KM
title A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 era
title_full A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 era
title_fullStr A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 era
title_full_unstemmed A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 era
title_short A possible role for immunogenetic factors in myositis developing after vaccination in the pre-covid-19 era
title_sort possible role for immunogenetic factors in myositis developing after vaccination in the pre covid 19 era
topic polymyositis
dermatomyositis
vaccination
adverse events
HLA
GM/KM
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1539659/full
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