Arthritis in Two Patients With Partial Recombination Activating Gene Deficiency

Frontiers in Pediatrics

卷:7

Svetlana Sharapova¹  Stefan Stefanov²  Sinisa Savic³  Naumova Elissaveta⁴  Mihailova Snezhina⁴  Krisztian Csomos⁵  Boglarka Ujhazi⁶  Kevin Y. Wu⁶  Maryssa Ellison⁶  Diana Milojevic⁷  Jolan E. Walter⁸  Pooja Purswani⁸  Ravishankar Sargur⁹ 

[1] Belarusian Research Center for Pediatric Oncology, Minsk, Belarus;

[2] Clinic of Rheumatology, Cardiology and Hematology, University Pediatric Hospital, Medical University, Sofia, Bulgaria;

[3] Department of Clinical Immunology and Allergy, Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James's University Hospital, Leeds, United Kingdom;

[4] Department of Clinical Immunology, University Hospital Alexandrovska, Medical University, Sofia, Bulgaria;

[5] Department of Pediatrics, University of South Florida, St. Petersburg, FL, United States;

[6] Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, United States;

[7] Division of Rheumatology, Department of Medicine, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States;

[8] Johns Hopkins All Children's Hospital Children's Research Institute, St. Petersburg, FL, United States;

[9] Sheffield Teaching Hospitals Foundation NHS Trust, Leeds, United Kingdom;

关键词: recombination activating gene;    RAG deficiency;    rheumatoid arthritis;    primary immunodeficiency;    tocilizumab;    refractory arthritis;   

DOI  :  10.3389/fped.2019.00235

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown