Wu Kevin Y, Purswani Pooja, Ujhazi Boglarka, Csomos Krisztian, Snezhina Mihailova, Elissaveta Naumova, Stefanov Stefan, Sharapova Svetlana, Ellison Maryssa, Milojevic Diana, Savic Sinisa, Sargur Ravishankar, Walter Jolan E
Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, United States.
Johns Hopkins All Children's Hospital Children's Research Institute, St. Petersburg, FL, United States.
Front Pediatr. 2019 Jul 5;7:235. doi: 10.3389/fped.2019.00235. eCollection 2019.
Autoimmunity is becoming an increasingly recognized complication in patients with primary immunodeficiencies (PIDs), including a variety of combined immune deficiencies such as Recombination Activating Gene (RAG) defects. The approach to treating autoimmunity in PID patients is complex, requiring a balance between immunosuppression and susceptibility to infection. Inflammatory arthritis is a feature of immune dysregulation in many PIDs, and the optimal treatment may differ from first line therapies that usually consist of disease-modifying anti rheumatic drugs (DMARDs). An example of mechanism-based therapy of arthritis in PID uses blockade of IL-6 signaling with tocilizumab for patients with STAT 3 gain-of-function (GOF) mutation and augmented IL-6 pathway. Herein, we describe two PID cases with arthritis who were found to have defects in RAG. One patient with refractory inflammatory arthritis experienced remarkable improvement in symptoms with tocilizumab therapy. Arthritis can be a clinical feature of immune dysregulation in RAG deficiency, and tocilizumab therapy has been suggested to have utility in treatment of arthritis in RAG deficiency.
自身免疫正日益被认为是原发性免疫缺陷（PID）患者的一种并发症，包括多种联合免疫缺陷，如重组激活基因（RAG）缺陷。治疗PID患者自身免疫的方法很复杂，需要在免疫抑制和感染易感性之间取得平衡。炎性关节炎是许多PID中免疫失调的一个特征，其最佳治疗方法可能与通常由改善病情抗风湿药（DMARDs）组成的一线疗法不同。PID中基于机制的关节炎治疗的一个例子是，对于具有信号转导和转录激活因子3（STAT 3）功能获得性（GOF）突变且IL-6途径增强的患者，使用托珠单抗阻断IL-6信号传导。在此，我们描述了两例患有关节炎的PID病例，发现他们存在RAG缺陷。一名患有难治性炎性关节炎的患者在接受托珠单抗治疗后症状有显著改善。关节炎可能是RAG缺陷中免疫失调的临床特征，有人提出托珠单抗疗法在治疗RAG缺陷引起的关节炎方面具有效用。
