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Outcomes and treatment strategies for autoimmunity and hyperinflammation in patients with RAG deficiency

Farmer, JR; Foldvari, Z; Ujhazi, B; De Ravin, SS; Chen, K; Bleesing, JJH; Schuetz, C; ... Walter, JE; + view all (2019) Outcomes and treatment strategies for autoimmunity and hyperinflammation in patients with RAG deficiency. Journal of Allergy and Clinical Immunology: In Practice 10.1016/j.jaip.2019.02.038. Green open access

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Abstract

BACKGROUND: While autoimmunity and hyperinflammation secondary to recombinase activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. The majority of patients (55.6%) presented with more than one autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and autoimmune neutropenia (AN), respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in the majority of cases (64.7%, 73.7%, and 71.4% for AIHA, ITP, and AN, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multi-lineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.

Type: Article
Title: Outcomes and treatment strategies for autoimmunity and hyperinflammation in patients with RAG deficiency
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jaip.2019.02.038
Publisher version: https://doi.org/10.1016/j.jaip.2019.02.038
Language: English
Additional information: © 2019 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0).
Keywords: recombinase activating gene (RAG), severe combined immunodeficiency (SCID), immune dysregulation, autoimmune cytopenias, hematopoietic stem cell transplantation (HSCT)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10071040
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