Outcomes and Treatment Strategies for Autoimmunity and Hyperinflammation in Patients with RAG Deficiency.
Autoimmune cytopenias
Hematopoietic stem cell transplantation (HSCT)
Immune dysregulation
Recombination activating gene (RAG)
Severe combined immunodeficiency (SCID)
Journal
The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220
Informations de publication
Date de publication:
Historique:
received:
13
10
2018
revised:
15
02
2019
accepted:
19
02
2019
pubmed:
17
3
2019
medline:
25
9
2020
entrez:
17
3
2019
Statut:
ppublish
Résumé
Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. 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. Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 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, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, 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. Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.
Sections du résumé
BACKGROUND
Although autoimmunity and hyperinflammation secondary to recombination 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. Most patients (55.6%) presented with more than 1 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, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, 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. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.
Identifiants
pubmed: 30877075
pii: S2213-2198(19)30260-0
doi: 10.1016/j.jaip.2019.02.038
pmc: PMC6612449
mid: NIHMS1024055
pii:
doi:
Substances chimiques
Homeodomain Proteins
0
Immunosuppressive Agents
0
RAG-1 protein
128559-51-3
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1970-1985.e4Subventions
Organisme : NIAID NIH HHS
ID : K08 AI103035
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI100887
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR059703
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD043245
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL116275
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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