Lack of Association among Peptidyl Arginine Deiminase Type 4 Autoantibodies, <i>PADI4</i> Polymorphisms, and Clinical Characteristics in Rheumatoid Arthritis.

Abstract

We aimed to jointly investigate the role of antipeptidyl arginine deiminase type 4 antibodies (anti-PAD4) and polymorphisms in the <i>PADI4</i> gene together with clinical variables in rheumatoid arthritis (RA). Serum IgG autoantibodies to human recombinant PAD4 were identified by DELFIA technique in 745 patients with RA (366 available from previous studies). Genotyping of <i>PADI4</i> was performed using TaqMan assays in 945 patients and 1118 controls. Clinical data, anticitrullinated protein antibodies (ACPA) status, shared epitope status, and a combined genetic risk score were also available. Anti-PAD4 antibodies were detected in 193 (26%) of 745 patients with RA; 149 (77%) of these were also ACPA-positive. No association was observed between anti-PAD4 status and clinical characteristics, <i>PADI4</i> polymorphisms, or genetic risk scores after stratification for ACPA status. Taken together, the results from these combined serological, genetic, and clinical analyses suggest that anti-PAD4 appears to be a bystander autoantibody with no current clinical utility in RA.