Clinical Characteristics of IgE Deficiency Among Patients with Primary Immunodeficiencies: Findings from the USIDNET Registry.

BACKGROUND: IgE has been recognized to be implicated in immune regulation and tumor surveillance. However, the prevalence and clinical significance of IgE deficiency (IED, IgE ≤2 kU/L) in primary immunodeficiencies (PID) remain poorly defined. OBJECTIVE: To evaluate the frequency, laboratory features, and clinical features of IED patients with PID. METHODS: We analyzed 1,593 patients with PID from the USIDNET registry with available IgE levels. Demographic, laboratory, and clinical characteristics were compared between IED and non-IED (nIED) groups. RESULTS: IED was identified in 363 patients (22.8%). The highest IED proportion was observed in ataxia-telangiectasia (73%), Hyper-IgM syndrome (38.5%), X-linked agammaglobulinemia (38.3%), and common variable immunodeficiency (CVID) (34%). IED patients had higher frequencies of reduced IgA (61% vs. 21.7%, p<0.001), IgM (49.6% vs. 21%, p<0.001), and CD4 counts (23.8% vs. 19.4%, p=0.01), and were more likely to receive immunoglobulin replacement therapy (OR 2.49, 95% CI (1.79, 3.47), p<0.001) compared to nIED patients. IED was associated with increased odds of splenomegaly (OR 2.76, 95% CI (1.89, 4.03), p<0.001), neutropenia (OR 1.80, 95% CI (1.13, 2.87), p=0.01), and thrombocytopenia (OR 3.13, 95% CI (1.82, 5.38), p<0.001). Proportions and odds of infections and sepsis were similar between the groups. In CVID, IED was associated with higher odds of malignancy (9.4% vs. 3.5%, OR 2.89, 95% CI (1.13-7.46), p=0.03). CONCLUSION: IED may identify a subgroup of PID patients who have greater immune dysregulation than those with nIED. Further prospective studies are needed to determine whether IED has prognostic or risk-stratification value among patients with PID.