Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope Protein in Patients With Rheumatoid Arthritis.
Xiaoxing Wang, Amanda Hefton, Kathryn Ni, Kennedy C Ukadike, Michael A Bowen, Mary Eckert, Anne Stevens, Christian Lood, Tomas Mustelin
Author Information
Xiaoxing Wang: X. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Amanda Hefton: X. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Kathryn Ni: X. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Kennedy C Ukadike: X. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Michael A Bowen: M.A. Bowen, PhD, Product and Process Development, Allogene Therapeutics, San Francisco, California.
Mary Eckert: M. Eckert, BS, Seattle Children's Research Institute, Seattle, Washington.
Anne Stevens: A. Stevens, MD, Professor, Seattle Children's Research Institute, Seattle, Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington, and Janssen Research & Development, LLC, Wayne, Pennsylvania, USA.
Christian Lood: X. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington. ORCID
Tomas Mustelin: X. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington; tomas2@uw.edu. ORCID
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.
