# Autoantibodies and Molecular Mimicry in Alphavirus Chronic Arthritis: A Systematic Review

## TL;DR

This review examines how alphavirus infections might lead to chronic arthritis through molecular mimicry and autoantibodies, but finds the evidence inconclusive.

## Contribution

The paper systematically reviews evidence for molecular mimicry and autoantibodies in alphavirus-induced chronic arthritis.

## Key findings

- Computational studies found similarities between alphavirus and human proteins, suggesting molecular mimicry.
- Clinical studies showed inconsistent autoantibody levels in chronic arthritis patients.
- Only one study found a significant link between autoantibodies and disease chronicity.

## Abstract

Chronic arthritis following arthritogenic alphavirus infections presents symptoms resembling autoimmune rheumatic diseases, raising questions about the underlying mechanisms, including molecular mimicry and autoantibody production. This systematic review evaluated evidence supporting molecular mimicry and the potential role of autoantibodies as predictive biomarkers in alphavirus-induced chronic arthritis. A comprehensive search of PubMed, Scopus and Web of Science was conducted following PRISMA 2020 guidelines and PECO framework. Thirteen studies met the inclusion criteria: four computational studies assessing peptide homology between viral and human proteins, and nine clinical studies evaluating autoantibodies in chronic post-alphavirus arthritis. Computational analyses identified conserved alphavirus peptides with sequence and structural similarity to human proteins implicated in autoimmunity, supporting the hypothesis of molecular mimicry. However, most lacked experimental validation. Clinical studies showed variable detection of autoantibodies, rheumatoid factors, anti-cyclic citrullinated peptide, and antinuclear antibodies in chronic patients, though seropositivity rates were inconsistent and generally low. Only one study reported a significant association between autoantibody levels and disease chronicity. The findings suggest a potential autoimmune component in post-alphavirus arthritis driven by molecular mimicry, though current evidence remains inconclusive due to methodological heterogeneity and limited validation. Autoantibodies may contribute to pathogenesis but are not reliable predictors of chronicity. Future longitudinal studies with standardized assays and validation of computational findings in human models are needed.