Heterogeneous immune cell composition in patients with combined immunodeficiency

IntroductionCombined immunodeficiencies (CIDs) are a severe class of inborn errors of immunity characterized by defective T cell development and function, often accompanied by impaired humoral and natural killer (NK) cell responses. Despite their shared clinical classification, the immunological heterogeneity within CIDs remains incompletely understood.

This study aims to characterize the immune cell landscape in CID patients caused by disease-causing mutations in different genes to identify immunophenotypic patterns.MethodsWe analyzed peripheral blood immune cells from four CID patients with disease-causing mutations in ARPC1B, EZR, BCL10, and IRF4 using mass cytometry. Unbiased computational approaches were used to profile major immune populations and their subsets, and results were compared with healthy control samples to identify differences in immune cell frequencies and phenotypes.ResultsAll patients retained major immune populations, but their relative frequencies differed significantly from those of healthy controls.

Patients with EZR and ARPC1B deficiency had markedly reduced CD4+ and CD8+ T cell frequencies, whereas the BCL10-deficient patient had a near absence of NK cells, highlighting mutation-specific immune distributions.