Potential clinical implications of molecular mimicry‐induced autoimmunity

Abstract

BackgroundMolecular mimicry is hypothesized to be a mechanism by which autoimmune diseases are triggered. It refers to sequence or structural homology between foreign antigens and self‐antigens, which can activate cross‐reactive lymphocytes that attack host tissues. Elucidating the role of molecular mimicry in human autoimmunity could have important clinical implications.ObjectiveTo review evidence for the role of molecular mimicry in major autoimmune diseases and discuss potential clinical implications.MethodsComprehensive literature review of clinical trials, observational studies, animal models, and immunology studies on molecular mimicry in multiple sclerosis, type 1 diabetes, rheumatoid arthritis, lupus, Guillain‐Barre syndrome, autoimmune myocarditis, and primary biliary cirrhosis published from 2000–2023.ResultsSubstantial indirect evidence supports molecular mimicry as a contributor to loss of self‐tolerance in several autoimmune conditions. Proposed microbial triggers include Epstein‐Barr virus, coxsackievirus, Campylobacter jejuni, and bacterial commensals. Key mechanisms involve cross‐reactive T cells and autoantibodies induced by epitope homology between microbial and self‐antigens. Perpetuation of autoimmunity involves epitope spreading, inflammatory mediators, and genetic factors.ConclusionsMolecular mimicry plausibly explains initial stages of autoimmune pathogenesis induced by infection or microbiota disturbances. Understanding mimicry antigens and pathways could enable improved prediction, monitoring, and antigen‐specific immunotherapy for autoimmune disorders. However, definitive proof of causation in humans remains limited. Further research should focus on establishing clinical evidence and utility.

Mapping the global research landscape on molecular mimicry: a visualization and bibliometric study

“…This suggests that molecular mimicry and the resulting cross-reactivity are very important [ 2 ]. A better understanding of molecular mimicry in this environment will greatly influence the diagnosis, prevention, and treatment of these diseases [ 3 ].…”

“…Because I am more interested in molecular mimicry as a novel idea in study than in related subjects, I used the terms “molecular mimicry” and its synonyms as my key words. The MeSH terms in PubMed and the findings of earlier studies on molecular mimicry were used to determine the relevant keywords [ 3 , 9 – 11 ]. The date of data mining was May 14, 2024.…”