Journal of translational autoimmunity · 2025
Immune responses to infection and autoimmune diseases in the UK biobank.
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Yun Choa, Yoon Dongwon, Jung Sun Young, Kim Moonsuk, Beydoun May A, Launer Lenore, Song Minkyo
Аннотация
BACKGROUND: Infections may trigger autoimmunity, but large-scale studies on antibodies to infections and their associations with autoimmune diseases are limited. We aim to better understand the etiologic role of infection.
METHODS: We analyzed 9429 UK Biobank participants for 45 antibody responses to 20 pathogens. Association between seropositivity and autoimmune diseases was assessed with logistic regression for prevalence and Cox regression for incidence, applying Bonferroni correction. 49 autoimmune diseases were ascertained via International Classification of Diseases codes and self-reported diagnoses, of which 14 were analyzed.
RESULTS: At baseline, 671 (7.1 %, 58 % female) had at least one autoimmune disease. In males, HSV-1 seropositivity was linked to lower odds of rheumatic fever/rheumatic heart disease (odds ratio 0.29 [95 % CI 0.12-0.68]), at Bonferroni significance. At nominal significance (p < 0.05), eight associations were observed-positive: HHV-6B-type 1 diabetes, H. pylori-sarcoidosis, HPV-18-type 1 diabetes, JCV-psoriasis; inverse: T. gondii-celiac disease, H. pylori-Crohn's disease, HSV-1-multiple sclerosis, HHV-7-rheumatoid arthritis. Of 8758 autoimmune disease-free individuals, 627 developed autoimmune diseases. In females, seropositivity to HPV-18 was associated with rheumatoid arthritis (hazard ratio 2.26 [95 % CI 1.34-3.82]), at Bonferroni significance. HRs for 3 nominal seropositivity/autoimmune disease associations (1 inverse, 2 positive) ranged from 0.42 [95 % CI 0.21-0.87] (HHV-6B/vasculitis) to 3.62 [95 % CI 1.29-10.12] (C. trachomatis/psoriasis) in both sexes.
CONCLUSIONS: This study examined cross-sectional and prospective associations between antibodies to infectious agents and autoimmune diseases. Inverse associations may suggest infections could train the immune system or reflect altered host immunity, while positive associations indicate potential autoimmune triggers. These findings enhance understanding of autoimmune disease etiology and provide a foundation for future mechanistic studies and hypothesis-driven research.
METHODS: We analyzed 9429 UK Biobank participants for 45 antibody responses to 20 pathogens. Association between seropositivity and autoimmune diseases was assessed with logistic regression for prevalence and Cox regression for incidence, applying Bonferroni correction. 49 autoimmune diseases were ascertained via International Classification of Diseases codes and self-reported diagnoses, of which 14 were analyzed.
RESULTS: At baseline, 671 (7.1 %, 58 % female) had at least one autoimmune disease. In males, HSV-1 seropositivity was linked to lower odds of rheumatic fever/rheumatic heart disease (odds ratio 0.29 [95 % CI 0.12-0.68]), at Bonferroni significance. At nominal significance (p < 0.05), eight associations were observed-positive: HHV-6B-type 1 diabetes, H. pylori-sarcoidosis, HPV-18-type 1 diabetes, JCV-psoriasis; inverse: T. gondii-celiac disease, H. pylori-Crohn's disease, HSV-1-multiple sclerosis, HHV-7-rheumatoid arthritis. Of 8758 autoimmune disease-free individuals, 627 developed autoimmune diseases. In females, seropositivity to HPV-18 was associated with rheumatoid arthritis (hazard ratio 2.26 [95 % CI 1.34-3.82]), at Bonferroni significance. HRs for 3 nominal seropositivity/autoimmune disease associations (1 inverse, 2 positive) ranged from 0.42 [95 % CI 0.21-0.87] (HHV-6B/vasculitis) to 3.62 [95 % CI 1.29-10.12] (C. trachomatis/psoriasis) in both sexes.
CONCLUSIONS: This study examined cross-sectional and prospective associations between antibodies to infectious agents and autoimmune diseases. Inverse associations may suggest infections could train the immune system or reflect altered host immunity, while positive associations indicate potential autoimmune triggers. These findings enhance understanding of autoimmune disease etiology and provide a foundation for future mechanistic studies and hypothesis-driven research.