RT Journal Article
SR Electronic
T1 Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope Protein in Patients With Rheumatoid Arthritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.201492
DO 10.3899/jrheum.201492
A1 Xiaoxing Wang
A1 Amanda Hefton
A1 Kathryn Ni
A1 Kennedy C.  Ukadike
A1 Michael A.  Bowen
A1 Mary Eckert
A1 Anne Stevens
A1 Christian Lood
A1 Tomas Mustelin
YR 2021
UL http://www.jrheum.org/content/early/2021/10/10/jrheum.201492.abstract
AB Objective Autoantibodies against proteins encoded by human endogenous retrovirus K (HERV-K) have been reported in patients with rheumatoid arthritis (RA), but their relevance, if any, has remained unresolved. We revisited this question and tested if such autoantibodies may react with citrullinated epitopes on the envelope (Env) protein of HERV-K. Methods Immunoblotting and ELISAs were conducted with unmodified Env protein and with Env citrullinated by protein arginine deiminase 4 (PAD4). Sera from 100 patients with RA, plasma from 32 patients with juvenile idiopathic arthritis (JIA), and healthy adult and pediatric controls were included. Antibody reactivity was evaluated for correlations with clinical and laboratory variables of the patients. Results We replicated and expanded upon published data suggesting that patients with RA or JIA have autoantibodies against HERV-K Env, some with high titers. Anti-HERV-K antibodies correlated with cigarette smoking and with circulating myeloperoxidase-DNA complexes indicative of nonapoptotic neutrophil cell death. Further, most of the patients with RA, but not those with JIA, had autoantibodies that reacted more strongly with Env that was citrullinated by PAD4. These anticitrullinated Env autoantibodies correlated with seropositivity and tended to be higher in patients with erosive disease. Conclusion Our data suggest that anti-HERV-K immunity is elevated in RA and JIA and may have a connection with pathogenic protein citrullination in RA.