Total IgE levels are associated with mortality risk partially mediated by vitamin status: A nationally representative population-based study.

Background and aims: Elevated total IgE levels are traditionally associated with allergic conditions; however, their potential role as biomarker for mortality risk beyond allergic diseases has not been extensively explored. Recent studies have suggested that IgE is associated with cardiovascular (CV) disease. We aimed to investigate the association between total IgE levels and the risk of all-cause and cause-specific mortality, as well as to explore the potential mediating role of vitamin status in these associations.

Methods and results: The association between IgE and mortality risk was examined in the National Health and Examination Survey 2005-2006. Weighted multivariable Cox proportional hazards model was employed. We further performed restricted cubic spline analysis to assess dose-response relationships and conducted mediation analysis to explore the influence of vitamins on IgE-related mortality risk. Individuals in the highest total IgE quantile (>107.0 kU/L) exhibited a 32 % increased risk of all-cause mortality (95 % CI: 1.07-1.64) and a 98 % elevated risk of CV mortality (95 % CI: 1.28-3.07) compared to the lowest quantile (<14.5 kU/L). Heterogeneity exists in the dose-response relationship and threshold effects among individuals with and without allergic diseases. Vitamin deficiency is associated with elevated total IgE levels, and vitamins mediated the relationship of the IgE-related all-cause mortality with the proportion of mediation ranging from 4.68 to 12.71 %.

Conclusions: Our findings introduce a novel dimension to the understanding of IgE as a biomarker for mortality beyond its traditional role in allergic diseases, challenging the current paradigm that elevated IgE levels without overt allergic symptoms are benign.