Peptidylarginine deiminase 4 (PADI4) identified as a conformation-dependent autoantigen in rheumatoid arthritis.
OBJECTIVE
Peptidylarginine deiminase (PADI) catalyses the post-translational modification of arginine to citrulline, which is specifically recognized by sera from rheumatoid arthritis (RA) patients. The PADI4 gene has recently been identified as a risk factor for RA. We aimed to determine whether PADI4 constitutes an autoantigen in RA.


METHODS
Serum samples were obtained from 42 patients with RA, 19 patients with systemic lupus erythematosus (SLE), 23 patients with other rheumatic diseases, and 40 normal individuals. The presence of antibodies against recombinant human PADI4 (anti-PADI4) was examined using enzyme-linked immunosorbent assay (ELISA) and Western blotting.


RESULTS
For ELISA, the prevalence of anti-PADI4 among RA patients (50%) was significantly higher than that of normal individuals (2.5%), SLE (10.5%), and other rheumatic diseases (4.3%), while for Western blot analysis, PADI4 was recognized only by a portion of the ELISA-positive serum samples.


CONCLUSIONS
PADI4 is an autoantigen in some RA patients, and its conformational epitope(s) may be important.
Takizawa
Y
Y
Department of Allergy and Rheumatology, University of Tokyo School of Medicine, Tokyo, Japan.
Sawada
T
T
Suzuki
A
A
Yamada
R
R
Inoue
T
T
Yamamoto
K
K
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000276:immunology* / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011487:Protein Conformation; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
D001324:Autoantigens; D000939:Epitopes; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases