The pathogenesis of rheumatoid arthritis

Stefano Alivernini, Gary S. Firestein, Iain B. Mcinnes*

*Corresponding author

Research output: Contribution to journalArticle


Significant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of targeted-biologic and -synthetic disease modifying antirheumatic drugs (DMARDs) has also transformed clinical outcomes. Despite this, RA remains a life-long disease without a cure. Unmet needs include partial response and non-response to treatment in many patients, failure to achieve immune homeostasis or drug free remission, and inability to repair damaged tissues. RA is now recognized as the end of a multi-year prodromal phase in which systemic immune dysregulation, likely beginning in mucosal surfaces, is followed by a symptomatic clinical phase. Inflammation and immune reactivity are primarily localized to the synovium leading to pain and articular damage, but is also associated with a broader series of comorbidities. Here, we review recently described immunologic mechanisms that drive breach of tolerance, chronic synovitis, and remission.
Original languageEnglish
Pages (from-to)2255-2270
Number of pages16
Publication statusPublished - 2022


  • arthritis
  • disease
  • inflammation
  • pathogenesis
  • rheumatoid


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