Evaluation of the clinical and laboratory factors affecting the prognosis of severe combined immune deficiencies

Background and Aim: Severe combined immunodeficiencies (SCIDs) are primary immunodeficiencies characterized by absence or loss of function in T and/or B cells. The long-term results of the SCID disease spectrum have been evaluated in few studies. We sought to evaluate the pre- and post-transplant manifestations of SCID patients and determine factors that have impact on the paients' survival. Method: We included 54 SCID patients (classical SCID, atypical ASCID, Omenn syndrome), followed at Marmara University Department of Pediatric Allergy and Immunology to this study. We retrieved patients' features for their medical records. T cell receptor repertoires were analyzed by flow cytometry. Results: The age of patients at diagnosis was 25,2±53,2 months and follow-up time was 40,06±44,04 months. Symptom onset and diagnostic ages were significantly high in atypical SCID (p=0.001; p<0.001), and also autoimmune manifestations were more common in this group (p=0,016). The most common disease form was T-B-NK+, and RAG (recombination activating) gene mutation was the prominent genetic defect among patients. Overall survival rate was %82,1±7. Peripheral blood stem cell source and genotype other than RAG had significant impact on CD4+T cells immune reconstitution after transplantation (p=0,044, p=0,035; respectively). Phenotypical donors and peripheral blood stem cell source provided significantly high B-cell reconstitution (p=0,002, p=0,028). Furthermore, conditioning regimen had better B-cell reconstitution (p=0,003). Post-transplant T-cell receptor diversity was sufficient in the patients and showed an equal distribution pattern as healthy controls. Overall survival rate was lower in patients who were transplanted during active infection or received stem cells source from mismatched donors (p=0,030, p=0,015). Conclusions: Early diagnosis and timely transplantation of SCID patients will offer better prognosis. The clinical and laboratory markers determined in our study are helpful to guide the physicians during treatment of patients and for the prediction of the prognosis. Keywords: Severe combined immune deficiencies, bone marrow transplantation, immune reconstitution, T cell repertoire, prognosis