TY - JOUR
T1 - Clinical and Laboratory Factors Affecting the Prognosis of Severe Combined Immunodeficiency
AU - Ozturk, Elif
AU - Catak, Mehmet Cihangir
AU - Kiykim, Ayca
AU - Baser, Dilek
AU - Bilgic Eltan, Sevgi
AU - Yalcin, Koray
AU - Kasap, Nurhan
AU - Nain, Ercan
AU - Bulutoglu, Alper
AU - Akgun, Gamze
AU - Can, Yasemin
AU - Sefer, Asena Pinar
AU - Babayeva, Royala
AU - Caki-Kilic, Suar
AU - Tezcan Karasu, Gulsun
AU - Yesilipek, Akif
AU - Ozen, Ahmet
AU - Karakoc-Aydiner, Elif
AU - Baris, Safa
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/7
Y1 - 2022/7
N2 - Purpose: Severe combined immunodeficiency (SCID) is one of the most severe forms of inborn errors of immunity characterized by absence or loss of function in T cells. The long-term outcomes of all forms of SCID have been evaluated in a limited number of studies. We aimed to evaluate the pre- and post-transplant manifestations of SCID patients and determine the factors affecting the survival of patients. Methods: We included 54 SCID patients (classical SCID, Omenn syndrome, atypical SCID (AS)) in this study. We evaluated the clinical presentation, infections, and outcome of hematopoietic stem cell transplantation (HSCT). Lymphocyte subsets and T-cell receptor (TCR) repertoire were analyzed by flow cytometry. Results: The median age at diagnosis was 5 (range: 3–24) months and follow-up time was 25 (range: 5–61) months. Symptom onset and diagnostic ages were significantly higher in AS compared to others (p = 0.001; p < 0.001). The most common SCID phenotype was T-B-NK + , and mutations in recombination-activating genes (RAG1/2) were the prominent genetic defect among patients. The overall survival (OS) rate was 83.3% after HSCT, higher than in non-transplanted patients (p = 0.001). Peripheral blood stem cell sources and genotypes other than RAG had a significant favorable impact on CD4+ T cells immune reconstitution after transplantation (p = 0.044, p = 0.035; respectively). Gender matching transplantations from human leukocyte antigen (HLA)–identical and non-identical donors and using peripheral blood stem cell source yielded higher B-cell reconstitution (p = 0.002, p = 0.028; respectively). Furthermore, receiving a conditioning regimen provided better B-cell reconstitution and chimerism (p = 0.003, p = 0.001). Post-transplant TCR diversity was sufficient in the patients and showed an equal distribution pattern as healthy controls. The OS rate was lower in patients who underwent transplant with active infection or received stem cells from mismatched donors (p = 0.030, p = 0.015; respectively). Conclusion: This study identifies diagnostic and therapeutic approaches predictive of favorable outcomes for patients with SCID.
AB - Purpose: Severe combined immunodeficiency (SCID) is one of the most severe forms of inborn errors of immunity characterized by absence or loss of function in T cells. The long-term outcomes of all forms of SCID have been evaluated in a limited number of studies. We aimed to evaluate the pre- and post-transplant manifestations of SCID patients and determine the factors affecting the survival of patients. Methods: We included 54 SCID patients (classical SCID, Omenn syndrome, atypical SCID (AS)) in this study. We evaluated the clinical presentation, infections, and outcome of hematopoietic stem cell transplantation (HSCT). Lymphocyte subsets and T-cell receptor (TCR) repertoire were analyzed by flow cytometry. Results: The median age at diagnosis was 5 (range: 3–24) months and follow-up time was 25 (range: 5–61) months. Symptom onset and diagnostic ages were significantly higher in AS compared to others (p = 0.001; p < 0.001). The most common SCID phenotype was T-B-NK + , and mutations in recombination-activating genes (RAG1/2) were the prominent genetic defect among patients. The overall survival (OS) rate was 83.3% after HSCT, higher than in non-transplanted patients (p = 0.001). Peripheral blood stem cell sources and genotypes other than RAG had a significant favorable impact on CD4+ T cells immune reconstitution after transplantation (p = 0.044, p = 0.035; respectively). Gender matching transplantations from human leukocyte antigen (HLA)–identical and non-identical donors and using peripheral blood stem cell source yielded higher B-cell reconstitution (p = 0.002, p = 0.028; respectively). Furthermore, receiving a conditioning regimen provided better B-cell reconstitution and chimerism (p = 0.003, p = 0.001). Post-transplant TCR diversity was sufficient in the patients and showed an equal distribution pattern as healthy controls. The OS rate was lower in patients who underwent transplant with active infection or received stem cells from mismatched donors (p = 0.030, p = 0.015; respectively). Conclusion: This study identifies diagnostic and therapeutic approaches predictive of favorable outcomes for patients with SCID.
KW - Bone marrow transplantation
KW - Immune reconstitution
KW - Prognosis
KW - Severe combined immunodeficiency
KW - T-cell receptor repertoire
UR - http://www.scopus.com/inward/record.url?scp=85128788991&partnerID=8YFLogxK
U2 - 10.1007/s10875-022-01262-0
DO - 10.1007/s10875-022-01262-0
M3 - Article
C2 - 35451701
AN - SCOPUS:85128788991
SN - 0271-9142
VL - 42
SP - 1036
EP - 1050
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
IS - 5
ER -