Your browser doesn't support javascript.
loading
Factors predisposing to humoral autoimmunity against brain-antigens in health and disease: Analysis of 49 autoantibodies in over 7000 subjects.
Daguano Gastaldi, Vinicius; Bh Wilke, Justus; Weidinger, Cosima A; Walter, Carolin; Barnkothe, Nadine; Teegen, Bianca; Luessi, Felix; Stöcker, Winfried; Lühder, Fred; Begemann, Martin; Zipp, Frauke; Nave, Klaus-Armin; Ehrenreich, Hannelore.
Afiliación
  • Daguano Gastaldi V; Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
  • Bh Wilke J; Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
  • Weidinger CA; Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
  • Walter C; Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
  • Barnkothe N; Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
  • Teegen B; Institute for Experimental Immunology, Affiliated to Euroimmun, Lübeck, Germany.
  • Luessi F; Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine­Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
  • Stöcker W; Institute for Experimental Immunology, Affiliated to Euroimmun, Lübeck, Germany.
  • Lühder F; Institute of Neuroimmunology and Multiple Sclerosis Research, University Medical Center, of the Georg August University, Göttingen, Germany.
  • Begemann M; Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
  • Zipp F; Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine­Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
  • Nave KA; Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
  • Ehrenreich H; Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany. Electronic address: ehrenreich@mpinat.mpg.de.
Brain Behav Immun ; 108: 135-147, 2023 Feb.
Article en En | MEDLINE | ID: mdl-36323361
BACKGROUND: Circulating autoantibodies (AB) against brain-antigens, often deemed pathological, receive increasing attention. We assessed predispositions and seroprevalence/characteristics of 49 AB in > 7000 individuals. METHODS: Exploratory cross-sectional cohort study, investigating deeply phenotyped neuropsychiatric patients and healthy individuals of GRAS Data Collection for presence/characteristics of 49 brain-directed serum-AB. Predispositions were evaluated through GWAS of NMDAR1-AB carriers, analyses of immune check-point genotypes, APOE4 status, neurotrauma. Chi-square, Fisher's exact tests and logistic regression analyses were used. RESULTS: Study of N = 7025 subjects (55.8 % male; 41 ±â€¯16 years) revealed N = 1133 (16.13 %) carriers of any AB against 49 defined brain-antigens. Overall, age dependence of seroprevalence (OR = 1.018/year; 95 % CI [1.015-1.022]) emerged, but no disease association, neither general nor with neuropsychiatric subgroups. Males had higher AB seroprevalence (OR = 1.303; 95 % CI [1.144-1.486]). Immunoglobulin class (N for IgM:462; IgA:487; IgG:477) and titers were similar. Abundant were NMDAR1-AB (7.7 %). Low seroprevalence (1.25 %-0.02 %) was seen for most AB (e.g., amphiphysin, KCNA2, ARHGAP26, GFAP, CASPR2, MOG, Homer-3, KCNA1, GLRA1b, GAD65). Non-detectable were others. GWAS of NMDAR1-AB carriers revealed three genome-wide significant SNPs, two intergenic, one in TENM3, previously autoimmune disease-associated. Targeted analysis of immune check-point genotypes (CTLA4, PD1, PD-L1) uncovered effects on humoral anti-brain autoimmunity (OR = 1.55; 95 % CI [1.058-2.271]) and disease likelihood (OR = 1.43; 95 % CI [1.032-1.985]). APOE4 carriers (∼19 %) had lower seropositivity (OR = 0.766; 95 % CI [0.625-0.933]). Neurotrauma predisposed to NMDAR1-AB seroprevalence (IgM: OR = 1.599; 95 % CI [1.022-2.468]). CONCLUSIONS: Humoral autoimmunity against brain-antigens, frequent across health and disease, is predicted by age, gender, genetic predisposition, and brain injury. Seroprevalence, immunoglobulin class, or titers do not predict disease.
Asunto(s)
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Autoanticuerpos / Autoinmunidad Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Autoanticuerpos / Autoinmunidad Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Alemania