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

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.

To evaluate the frequency, laboratory features, and clinical features of IED patients with PID.

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.

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).

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.