Background/Purpose: In order to identify the individuals at risk of imminent progression to rheumatoid arthritis (RA), EULAR has established a definition of clinically suspect arthralgia (CSA). Individuals carrying autoantibodies e.g. anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) are at high risk of developing RA. Peptidyl arginine deaminases (PAD) are enzymes responsible for producing autoantigens by citrullination of proteins and, importantly, may themselves represent as an autoantigen. Similar to ACPA and RF, anti-PAD antibodies are detectable years before the disease onset. We aimed to determine the prevalence of anti-PAD autoantibodies and their coincidence with RF and ACPA in sera of the individuals at risk-of developing RA.

Methods: Our prospective study included 86 individuals at-risk of progression to RA defined as having arthralgia without arthritis and being either ACPA+ or meeting the clinical CSA definition. Antibodies against PAD3 and PAD4 were analyzed in serum using commercially available ELISA kit (MyBioSource).

Results: Of the 86 at-risk individuals, 65 were seropositive (RF+ and/or ACPA+) and 54 met the CSA definition (33 were seropositive) with median duration of arthralgia 12 months. Of all individuals, 30 (34.8%) were anti-PAD+ (specifically, 14% were anti-PAD3+ and 21% were anti-PAD4+). Of 21 individuals who were both RF+ and ACPA+, 57% were anti-PAD+. Thirty % of RF- and 26% of ACPA- individuals were anti-PAD+. Of 21 seronegative (RF- and ACPA-) individuals, 33% were anti-PAD+. A third of individuals who met the CSA definition were anti-PAD+, irrespective of RF and ACPA positivity, 33% of seropositive CSA individuals were also anti-PAD+.

Sixteen patients progressed to RA within a median of 7.5 months of follow up with median DAS28(CRP) 2.28. Of these, 14 were RF+ and/or ACPA+ and 9 were anti-PAD+. All RF, ACPA and anti-PAD autoantibodies were positive in 5 individuals, both seronegative individuals were also anti-PAD-.

Conclusion: A third of the at-risk individuals with arthralgia, originally assessed as seronegative, were carriers of anti-PAD autoantibodies, however, none of them was both anti-PAD3 and anti-PAD4 positive. Similarly, a third of seropositive at-risk individuals were anti-PAD positive. The predictive value of anti-PAD antibodies for future development of RA in the at-risk individuals with arthralgia needs to be investigated.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-peptidylarginine-deaminase-antibodies-in-the-individuals-with-arthralgia-at-risk-of-progression-to-rheumatoid-arthritis/