Am J Arthritis | Volume 1, Issue 2 | Review Article | Open Access

Citrullinated Proteins are Arthritogenic Autoantigens in Rheumatoid Arthritis

Lazaros I Sakkas1*, George Vaiopoulos2 and Dimitrios P Bogdanos1

1School of Health Sciences, University of Thessaly, Larissa, Greece
2Medical School, National and Kapodistrian University of Athens, Greece

*Correspondance to: Lazaros I Sakkas 

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Both genetic and environmental factors are implicated for the development of Rheumatoid Arthritis (RA). The association of RA with HLA-DRB1 shared epitope (SE) suggests that T cells recognize an antigen presented on HLA-DRB1SE allele. The discovery of Anti Citrullinated Peptide Antibodies (ACPAs) greatly advanced our understanding of RA pathogenesis. ACPAs, including ACPAs against peptides derived from Epstein-Barr Virus (EBV), appear many years before the onset of clinical RA and are associated with severe disease. Citrullination is the conversion of arginine residues to citrulline in proteins, mediated by Peptidyl Arginine Deiminases (PADs). Citrullination increases the peptide binding affinity to HLA-DRB1SE that can activate T cells and provide help to B cells for ACPA production and there is increased frequency of T cells recognizing citrullinated (cit) peptides in ACPA + RA. Periodontal Disease (PD), a risk factor for RA, can provide cit neoantigens. Porphyromonas gingivalis, a causative agent for PD, expresses PAD (PPAD), and arginine ginpains (Rgps) which preferentially cleave proteins at terminal arginine residues. Cross-reactivity was detected between ACPAs against P. gingivalis or EBV peptides and human peptides which can re-direct immune response to self-antigens. There is some evidence suggesting that ACPAs are arthritogenic. In animal models, cit peptides can cause or exacerbate arthritis in a HLA-DRB1SErestricted manner. ACPAs can also activate macrophages and cause bone resorption.


Anti-cyclic citrullinated antibodies; Autoantigen; Autoantibody; Rheumatoid arthritis


Sakkas LI, Vaiopoulos G, Bogdanos DP. Citrullinated Proteins are Arthritogenic Autoantigens in Rheumatoid Arthritis. Am J Arthritis. 2017;1(2):1007.

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