Activation of circulating γδ T cells in pediatric IgA vasculitis nephritis links the IL-17 A+ subset to renal risk

Renal involvement is a key determinant of prognosis in IgA vasculitis (IgAV), yet its underlying immunologic mechanisms remain incompletely elucidated. The role of γδ T cells and their subsets requires clarification. The study enrolled 88 children between September 1, 2023, and September 1, 2025, categorized into three groups: IgAV with nephritis (IgAVN, n = 39), IgAV without nephritis (IgAVwoN, n = 36), and healthy controls (HC, n = 13). Flow cytometry was used to assess the percentage of peripheral blood γδ T cells, their surface phenotype (CD69, NKG2D, TLR4), and intracellular cytokines (IL-17 A, IL-10, TNF-α). Multivariable logistic regression identified independent risk factors, receiver operating characteristic curve analysis evaluated diagnostic performance, and correlation with 24-hour proteinuria was assessed. Patients with IgAVN exhibited a significantly increased frequency of total γδ T cells and an expanded CD69⁺ activated subset. TLR4 expression on γδ T cells was upregulated in IgAV patients compared to HC group, but did not differ significantly between the IgAVN and IgAVwoN groups. The IL-17 A producing γδ T cell subset was identified as an independent risk factor for IgAVN (OR = 1.202, 95% CI 1.014–1.424, P = 0.034). Its frequency positively correlated with 24-hour proteinuria levels ( r = 0.575, P < 0.01). This parameter demonstrated high specificity (97.22%) and moderate diagnostic accuracy (AUC = 0.673) for distinguishing IgAVN. IL-17 A⁺ γδ T cells were an independent risk factor for IgAVN and correlated with renal injury severity. While Th17 cells are the main IL-17 source, γδ T cells may represent an additional source. Further investigation is needed.