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In rheumatoid arthritis (RA), ectopic lymphoid structures (ELSs) within synovial joints sustain autoimmune reactions against locally expressed autoantigens. Findings now suggest that synovial stromal-derived autoantigens, such as heat shock protein 60 (HSP60), are targeted by pathogenic autoantibodies in RA and contribute to chronic inflammation and arthritis severity.
A subset of the anti-FLS RA-rmAbs was found to recognize HSP60 and showed some cross-reactivity with other stromal autoantigens such as calreticulin and vimentin, but not with citrullinated fibrinogen. In a mouse model of collagen-induced arthritis, these anti-HSP60 RA-rmAbs exacerbated arthritis, indicating their pathogenic potential.
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