Morbidity, Mortality, and Therapeutics in Combined Immunodeficiency: Data from the USIDNET Registry

Document Type

Journal Article

Publication Date



The journal of allergy and clinical immunology. In practice




Combined Immunodeficiency; Hematopoietic Stem Cell Transplantation; Mortality; USIDNET


BACKGROUND: Optimal management of patients with combined immunodeficiency (CID), especially pertaining to hematopoietic stem cell transplant (HSCT), remains unclear. OBJECTIVE: Our purpose was to identify factors influencing HSCT and mortality in the CID population in North America. METHODS: We identified 337 participants in the USIDNET database with diverse forms of CID and their characteristics, including demographics, laboratory values, infectious history, comorbidities, and treatment strategies. Univariate analysis was performed using logistic regression, while multivariate analysis was performed using multiple cox proportional hazards. RESULTS: On univariate analysis, disseminated invasive viral infections and variants in STAT3, GATA2, and DOCK8 were associated with increased odds of HSCT. Mucocutaneous fungal infections and variants in STAT3 were associated with increased odds of survival, while disseminated/invasive fungal infections, disseminated/invasive viral infections, and parasitic infections were associated with decreased odds of survival. On multiple variable cox proportional hazards analysis, variants in ZAP70, nonspecific bacterial, and disseminated/invasive viral infections were associated with increased hazards of transplantation; while variants in multiple genes (RMRP, NEMO, DOCK8, CD40L, and CARD9), disseminated/invasive viral infections, autoimmune disease, and higher absolute lymphocyte count were associated with increased hazards of death. Importantly, demographics, basic lymphocyte subset counts, and absence of genetic diagnosis were not associated with HSCT or mortality. CONCLUSION: We determined that specific genetic diagnoses and infection burden impacts the decision to undergo HSCT in this cohort. Additionally, certain genetic diagnoses and invasive viral infections carry an increased risk of mortality.