Increased soluble CD16b derived from activated neutrophils in plasma is associated with the pathogenesis and progression of IgA nephropathy.

CD16b (FcγIIIB) is an IgG receptor mainly found on neutrophils. When activated, neutrophils release CD16b into the bloodstream. This study evaluated the potential of plasma and urine CD16b levels as biomarkers for IgA nephropathy (IgAN), assessing susceptibility, severity, and prognosis. Two cohorts were analyzed: 40 patients from 2022-2023 and 85 patients from 2011-2018. Plasma CD16b levels were significantly higher in IgAN patients than in controls and were linked to rapid GFR decline. Blood mRNA sequencing showed upregulation of neutrophil-related genes, suggesting a role in CD16b cleavage. Neutrophils from IgAN patients, when stimulated with IgG-ICs, showed decreased surface CD16b and increased CD16b in supernatants. Stimulation also raised APRIL and BAFF in supernatants. PBMCs cultured with activated neutrophils showed higher levels of Gd-IgA1 and an increase in CD19+IgA+ B cells and CD38+ IgA+ plasma cells. Urinary CD16b was elevated in IgAN patients, and immunohistochemistry revealed CD16 and elastase in inflamed glomeruli of crescentic IgAN patients. Plasma CD16b-IgG complex levels were decreased, correlating positively with IgG and eGFR and negatively with proteinuria. These findings highlight soluble CD16b's clinical significance in IgAN and the role of neutrophil activation in its pathogenesis.