Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results 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%). Conclusion 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.

Cifaldi, C., Rivalta, B., Amodio, D., Mattia, A., Pacillo, L., Di Cesare, S., et al. (2022). Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients. JOURNAL OF CLINICAL IMMUNOLOGY [10.1007/s10875-021-01130-3].

Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients

Amodio D.;Di Cesare S.;Cotugno N.;Palumbo G.;Palma P.;Rossi P.;Di Matteo G.;Finocchi A.;Cancrini C.
2022-01-01

Abstract

Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results 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%). Conclusion 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.
2022
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
English
CID phenotypes
Cytopenia
Hypomorphic mutation
RAG deficiency
RAG1/RAG2
Cifaldi, C., Rivalta, B., Amodio, D., Mattia, A., Pacillo, L., Di Cesare, S., et al. (2022). Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients. JOURNAL OF CLINICAL IMMUNOLOGY [10.1007/s10875-021-01130-3].
Cifaldi, C; Rivalta, B; Amodio, D; Mattia, A; Pacillo, L; Di Cesare, S; Chiriaco, M; Ursu, Gm; Cotugno, N; Giancotta, C; Manno, Ec; Santilli, V; Zanga...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/281471
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