UNDETECTABLE IGE AS A SENTINEL BIOMARKER FOR HUMORAL IMMUNODEFICIENCY

Abstract

<h3>Introduction</h3> The clinical significance of undetectable IgE (<2 IU/mL) in patients with otherwise normal immunoglobulins is unclear. We hypothesize that undetectable IgE reflects an impairment in isotype switching that could portend future development of a broader defect in humoral immunity. <h3>Methods</h3> We recruited 17 healthy adults with IgE <2 IU/mL. We compared their response to immunization with a Salmonella typhi polysaccharide vaccine relative to 16 randomly selected adults with IgE >2 IU/mL. We assessed pre-and post-vaccine IgG titers 4-6 weeks after vaccination, with a normal Salmonella typhi IgG index (STIGG index) defined as a >2-fold increase in titers. We isolated peripheral blood lymphocytes from 14 patients with undetectable IgE and induced IgE production <i>in vitro</i> via stimulation with CD40 ligand (CD40L) and IL-4. IgE production was assessed through semi-quantitative PCR of ε-germline and IgE heavy chain transcripts. <h3>Results</h3> 4/17 patients with undetectable IgE had a STIGG index ≤2, compared with 0/16 patients in the control group (p-value = 0.0582, Fisher's exact test). ε-germline and IgE heavy chain mRNA were detected in peripheral lymphocytes from all of the assessed patients with undetectable IgE. <h3>Conclusion</h3> An impaired polysaccharide vaccine response occurred more frequently in patients with undetectable IgE than in patients with an IgE >2 IU/mL, but the difference in this small pilot study was nonsignificant. A larger sample size is needed to clarify these findings. Peripheral blood lymphocytes isolated from patients with undetectable IgE are capable of producing IgE transcripts in response to CD40L/IL-4 stimulation.