Relaciones causales bidireccionales entre las respuestas inmunitarias mediadas por anticuerpos y las enfermedades...

Área de la Ciencia:

• Immunology; Genetics; Epidemiology

Sus antecedentes:

• Autoimmune diseases, including systemic lupus erythematosus (SLE) and multiple sclerosis (MS), arise from complex interactions between genetic predispositions and immune system dysregulation.; Antibody-mediated immune responses are increasingly recognized as critical components in the pathogenesis of these conditions.

Objetivo del estudio:

• To investigate the causal and bidirectional relationships between specific antibody-mediated immune responses and the risk of developing SLE and MS.; To elucidate the intricate interplay between pathogen-specific antibodies and autoimmune disease development.

Principales métodos:

• A bidirectional two-sample Mendelian randomization (MR) approach utilized genetic variants as instrumental variables.; Antibody data were sourced from the UK Biobank, and autoimmune disease data from the FinnGen database.; Generalized summary data-based MR and complementary MR methods, with Bonferroni correction, ensured robust and statistically significant findings.

Principales resultados:

• Elevated Epstein-Barr virus (EBV) EBNA-1 and ZEBRA antibodies correlated with decreased SLE risk.; Increased human herpesvirus 7 (HHV-7) U14 antibody levels were associated with higher SLE risk.; Higher EBV EBNA-1 antibody levels were linked to an increased risk of MS, and bidirectional analyses confirmed that SLE and MS influence antibody levels.

Conclusiones:

• This research establishes bidirectional relationships between antibody profiles and autoimmune diseases (SLE, MS).; Pathogen-specific antibody levels can act as either protective or risk factors, highlighting their dual role in disease.; Findings offer novel insights into the immunopathogenesis of SLE and MS, suggesting potential therapeutic targets.