Disease severity predicted by citrullinating enzyme

Antibodies to PAD-4 are an independent marker of severe rheumatoid arthritis (RA), with PAD-4 representing a potential therapeutic target, according to a recent study. Peptidyl arginine deiminase type 4 (PAD-4) is associated with the development of RA in some populations, although the authors point out that the underlying mechanism(s) s are unclear. To investigated further, the researchers analysed sera from 32 patients with established RA, 126 with other rheumatic diseases, and 32 healthy adults. Analysis revealed that the presence of auto-antibodies against PAD-4 independently and significantly predicted RA prognosis, with elevated levels of the auto-antibodies positively correlated with more severe joint damage and erosion. In particular, the researchers confirmed previous findings linking anti-PAD-4 antibodies to variation in the gene that encodes the PAD-4 enzyme, known as PADI4. "Taken together, these findings implicate unique PAD-4 structure and/or function in the generation of a PAD-4-specific immune response and, potentially, the downstream augmentation of joint damage in RA," the authors write. They conclude, "anti-PAD-4 antibodies are specific markers of RA, independently associated with more severe disease, suggesting that an anti-PAD-4 immune response may be involved in pathways of joint damage in this disease." Reference...