D2.380 - Incidental Low Serum IgE: A Marker of Underlying Inborn Errors of Immunity?

Immunoglobulin E (IgE) deficiency is defined as a serum IgE concentration below 2.5 IU/mL. Although low IgE levels are often detected incidentally and considered clinically insignificant, recent classifications of inborn errors of immunity (IEI) suggest that decreased IgE may indicate an underlying antibody deficiency and may be associated with additional immunological abnormalities. Therefore, the clinical significance of incidentally detected low IgE levels remains unclear and warrants further investigation.

This study aimed to investigate the potential association between incidentally detected low total IgE levels and IEI, and to evaluate the clinical and immunophenotypic characteristics of these patients. Medical records of patients with total serum IgE levels <2.5 IU/mL were retrospectively reviewed. Individuals with a prior diagnosis of IEI or a history of anti-IgE therapy were excluded. Demographic data, presenting complaints, accompanying allergic and autoimmune conditions, and detailed immunological parameters were analyzed to determine the presence of additional immunopathologies and to define the phenotypic profile of affected patients.

This retrospective analysis included 191 patients with total serum IgE levels below 2.5 IU/mL. Of these, 156 (81.7%) had isolated IgE deficiency, while 35 (18.3%) had additional immunopathologies (see Figure 1). No significant differences were observed between the groups regarding age, sex, presenting symptoms, asthma, allergic rhinitis, urticaria, autoimmune disease, or Jeffrey's warning signs (all p>0.05).

Patients with additional immunopathologies exhibited significantly lower median levels of IgA (p < 0.001), IgM (p = 0.02), and IgG2 (p = 0.004). Low isohemagglutinin titers (<1:8) were also significantly more frequent in this group (p = 0.001). No significant differences were detected in total IgG, IgG1, IgG3, IgG4, total lymphocyte counts, or T, B, and NK cell subsets. Naïve B-cell percentages tended to be higher in the additional immunopathologies group, approaching borderline significance (p = 0.058) (Table 1).

Although low total IgE levels are often isolated, about one-fifth of patients may present with additional immunological abnormalities. Comprehensive immunological evaluation and structured long-term follow-up can facilitate early detection of underlying IEI and timely clinical management.