Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients.
CID phenotypes
Cytopenia
Hypomorphic mutation
RAG deficiency
RAG1/RAG2
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
01
06
2021
accepted:
29
08
2021
pubmed:
20
10
2021
medline:
5
3
2022
entrez:
19
10
2021
Statut:
ppublish
Résumé
We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype-phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications.
Identifiants
pubmed: 34664192
doi: 10.1007/s10875-021-01130-3
pii: 10.1007/s10875-021-01130-3
pmc: PMC8821501
doi:
Substances chimiques
Homeodomain Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
130-145Informations de copyright
© 2021. The Author(s).
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