RAG deficiency is associated with a variety of clinical phenotypes. 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) respectively.
Patients represented a broad spectrum of RAG deficiencies: SCID n=8, OS n=6, LS/AS n=4 and CID n=4. Four novel mutation in RAG1 gene and one in RAG2 were reported.
The primary symptom at presentation were infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune/hyperinflammatory manifestations. Four patients experienced severe autoimmune cytopenia refractory to different lines of therapy.
Total lymphocytes count was reduced or almost lacking in SCID group. CD4 cells count was higher in OS patients. B lymphocytes were variably detected in AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%).
RAG deficiency still represents a challenge in the tracing of effective management and follow-up, notably considering the inability to predict the disease course in atypical cases. Immune dysregulation manifestations are common features often refractory to conventional medical management. 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.