Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients
| العنوان: | Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients |
|---|---|
| المؤلفون: | Emma Concetta Manno, Donato Amodio, Galaverna Federica, Carmela Giancotta, Gigliola Di Matteo, Giuseppe Palumbo, Silvia Di Cesare, Andrea Finocchi, Beatrice Rivalta, Algeri Mattia, Pietro Merli, Lucia Pacillo, Paola Zangari, Nicola Cotugno, Franco Locatelli, Maria Chiriaco, Veronica Santilli, Giorgiana Madalina Ursu, Cristina Cifaldi, Paolo Palma, Caterina Cancrini, Paolo Rossi |
| المصدر: | Journal of clinical immunology. 42(1) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, RAG deficiency, Immunology, medicine.disease_cause, Recombination-activating gene, Autoimmunity, Medical microbiology, RAG2, medicine, Immunology and Allergy, RAG1/RAG2, Humans, Hypomorphic mutation, Genetic Association Studies, Retrospective Studies, Homeodomain Proteins, Cytopenia, business.industry, Autoimmune Cytopenia, Immune dysregulation, medicine.disease, Settore MED/38, CID phenotypes, Phenotype, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Cohort, Mutation, Severe Combined Immunodeficiency, business |
| الوصف: | 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. |
| تدمد: | 1573-2592 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0971c65e89d6a47c596f3b9968f69473 https://pubmed.ncbi.nlm.nih.gov/34664192 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0971c65e89d6a47c596f3b9968f69473 |
| قاعدة البيانات: | OpenAIRE |
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