Profiling immune cell subsets in pediatric IgA vasculitis and immune thrombocytopenia: insights into disease pathogenesis and clinical correlates.

BACKGROUND

IgA vasculitis (IgAV) and immune thrombocytopenia (ITP) are common pediatric immune disorders with distinct clinical presentations. Their underlying peripheral immune signatures, particularly in relation to disease severity and etiology,remain incompletely characterized.

METHOD: We retrospectively analyzed peripheral blood mononuclear cell (PBMC) subsets from 125 children with IgAV and 35 with ITP using high-dimensional flow cytometry. Patients were stratified by disease severity, current glucocorticoid use at sampling, and etiology.

RESULTS

Compared with ITP, IgAV patients exhibited higher proportions of NK cells, classical monocytes, and activated B-cell subsets (CD38- CD25+ and CD38+ CD25+). Severe IgAV was characterized by pro-inflammatory helper T-cell polarization (increased Th9, Th17, and Th22 cells), regulatory B-cell depletion, elevated low-density granulocytes (LDGs), and reduced dendritic cells. Etiology-specific patterns included elevated ThGM-CSF cells in Haemophilus influenzae-associated IgAV. In ITP, severe cases showed increased monocyte proportions and distinct alterations in T-cell and NK-cell subsets, particularly within the autoantibody-associated (AAB) subgroup.

CONCLUSIONS

IgAV and ITP display markedly different immune profiles, with IgAV featuring polyclonal B-cell activation and granulocyte/NK-cell-mediated vascular inflammation, whereas ITP is associated with monocyte expansion in severe disease. Infection type and early glucocorticoid exposure significantly modulate these immune landscapes, providing a basis for stratified and personalized therapeutic strategies.

IMPACT: High-dimensional flow cytometry identifies stratified PBMC profiles in pediatric IgAV and ITP. Severe IgAV features pro-inflammatory Th9/Th17/Th22 polarization, regulatory B-cell depletion, and LDG elevation. Haemophilus influenzae infection is associated with elevated ThGM-CSF cells in IgAV. Severe ITP cases showed increased monocyte proportions and distinct alterations in T-cell and NK-cell subsets. Prior glucocorticoid exposure and infection type synergistically reshape immune subsets, supporting precision immunology approaches.