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.
M.A. Bowen, PhD, Product and Process Development, Allogene Therapeutics, San Francisco, California.
J Rheumatol. 2022 Jan;49(1):26-35. doi: 10.3899/jrheum.201492. Epub 2021 Aug 1.
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.
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.
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.
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.
已在类风湿关节炎（RA）患者中报告了针对人类内源性逆转录病毒 K（HERV-K）编码蛋白的自身抗体，但它们的相关性（如果有的话）仍未得到解决。我们重新研究了这个问题，并测试了这些自身抗体是否可能与 HERV-K 的包膜（Env）蛋白上的瓜氨酸化表位发生反应。
使用未经修饰的 Env 蛋白和经蛋白精氨酸脱亚氨酶 4（PAD4）瓜氨酸化的 Env 进行免疫印迹和 ELISA。纳入了 100 例 RA 患者、32 例幼年特发性关节炎（JIA）患者的血清以及健康成人和儿科对照者的血浆。评估了抗体反应与患者的临床和实验室变量的相关性。
我们复制并扩展了已发表的数据，表明 RA 或 JIA 患者存在针对 HERV-K Env 的自身抗体，其中一些具有高滴度。抗 HERV-K 抗体与吸烟以及循环髓过氧化物酶-DNA 复合物相关，后者提示非凋亡性中性粒细胞死亡。此外，大多数 RA 患者而非 JIA 患者具有与 PAD4 瓜氨酸化的 Env 反应更强的自身抗体。这些抗瓜氨酸化 Env 自身抗体与血清阳性相关，并且在有侵蚀性疾病的患者中倾向于更高。
我们的数据表明，抗 HERV-K 免疫在 RA 和 JIA 中升高，并且可能与 RA 中的致病性蛋白瓜氨酸化有关。
