J Clin Immunol. 2025 Jun 3;45(1):103. doi: 10.1007/s10875-025-01884-0.
ABSTRACT
BACKGROUND: DiGeorge Syndrome (DGS), a microdeletion syndrome, shows a broad spectrum from mild T-cell lymphopenia to severe combined immunodeficiency.
AIM: To define the clinical/immunophenotypical biomarkers for DGS.
PATIENTS AND METHODS: A total of 72 patients with 22q11.2 deletion(n = 66) and those fulfilling the DGS criteria without deletion (n = 6) were enrolled.
RESULTS: The male/female ratio was 41/31. Median age at clinical diagnosis was 1.7 years (0 days-22 years) with follow-up for 21.7 months (0 days-17.3 years). Common evaluation reasons were cardiac features (30.6%), failure to thrive (15.3%), and neurological features (15.3%). Craniofacial dysmorphism (64/66, 97%), central nervous system findings (62/72, 86.1%), and congenital cardiovascular defect (43/70, 61.4%) were common. We noted lymphopenia (30/72, 41.7%) and low IgM (25/69, 36.2%). T helper cell counts were low in 49.3% (33/67). T cytotoxic and NK cell counts were normal/high in 80.6% (54/67) and 97% (65/67) of patients, respectively. 42.3% (11/26) had low CD4 + TEMRA, and 34.6% (9/26) had low CD8 + TEM percentages. None had low CD8 + TEMRA. B cells were normal/high (52/67, 77.6%). 30.8%(8/26) had low switched-memory and 38.5% (10/26) had low active B cell percentages. Low IgA levels were associated with decreased lymphocyte activation and recent thymic emigrant (RTE) cell percentages. Six(8.3%) patients with lymphopenia, three of whom had congenital athymia, died.
CONCLUSION: CD4 lymphopenia was more common than CD8 lymphopenia. Normal/high CD8 + and NK cell counts were remarkable. Increased CD8+ TEMRA cells seem to indicate peripheral homeostatic proliferation following viral infections. Low serum IgA correlated with low RTE% and impaired T-cell function. DGS severity markers include hypocalcemia, congenital cardiac anomaly, and T-cell lymphopenia.
PMID:40461840 | DOI:10.1007/s10875-025-01884-0