Peptidylarginine deiminase, the arginine to citrulline converting enzyme, is frequently recognized by sera of patients with rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren syndrome

OBJECTIVE: Antibodies to citrulline-containing epitopes of filaggrin are highly specific for rheumatoid arthritis (RA). We studied whether the enzyme peptidylarginine deiminase (PAD), responsible for the post-translational modification of peptide-bound arginine residues to citrulline, constitutes an antigen for patients with RA. METHODS: IgG antibodies to PAD were measured by enzyme-linked immunosorbent assay (ELISA) in sera from patients with RA, systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), multiple sclerosis (MS) and healthy controls. RESULTS: Compared to healthy controls, raised levels of IgG antibodies to PAD were found in 50 of 57 recent-onset RA patients (88%) and in 40 (70%) of the same 57 patients 3 years later (p<0.0001 for both comparisons). Eleven of 51 (22%) patients with RA of long duration, 19/43 (44%) patients with SLE and 16/19 (84%) patients with pSS, but none of 20 patients with MS, had elevated anti-PAD levels. CONCLUSION: The arginine-citrulline converting enzyme PAD was recognized as a new antigen against which patients with inflammatory rheumatic diseases frequently show IgG class antibodies.