Putative approaches to bypass the citrulline-specific autoimmune response in rheumatoid arthritis

Smadar Gertel, Howard Amital

Research output: Contribution to journalReview articlepeer-review


The major autoantigens in the inflamed synovium in rheumatoid arthritis (RA) are citrullinated peptides. Citrullinated peptides are employed in diagnostic kits for detection of anti-citrullinated protein antibodies (ACPA), a serological marker with high specificity and sensitivity in the diagnosis of RA, and have been included in the new ACR/EULAR classification criteria for RA. ACPA-positive RA patients suffer from an erosive and more aggressive disease compared to ACPA-negative patients. In view of the mounting indications that ACPA plays a seminal role in the pathogenesis of RA, it might be valuable to pursue a specific treatment aiming ACPA as a target. We found that citrullinated peptides, which contain a unique amino acid, citrulline, alter the protein structure within the connective tissue, leading to tolerance breakdown and triggering the autoimmune response in RA. However, with different doses and routes of administration, citrullinated peptides can promote immune tolerance rather than induction of disease.

Original languageEnglish
Pages (from-to)587-590
Number of pages4
JournalIsrael Medical Association Journal
Issue number9
StatePublished - 1 Sep 2014


  • Anti-citrullinated protein antibodies (ACPA)
  • Inflammation
  • Peptides
  • Rheumatoid arthritis (RA)
  • Tolerance


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