Comprehensive analysis of B cell receptor repertoires reveals a distinct lambda light chain landscape in immunoglobulin A nephropathy

BACKGROUND: Immunoglobulin A nephropathy (IgAN) or Berger's disease is an autoimmune kidney disease. It is caused by the deposition of immunoglobulin A (IgA) in the kidney that results in glomerulonephritis and a gradual loss of renal functions. How antibodies/B cell receptors (BCRs) are involved in the pathogenesis of IgAN remains unclear, thus, to investigate BCR repertoire in IgAN is crucial to understand pathophysiological mechanisms of IgAN. METHODS: In this study, whole BCR repertoire, including BCR heavy (IGA, IGD, IGE, IGG, and IGM) and light (IGL and IGK) chains, were comprehensively profiled and analyzed in IgAN and non-IgA nephropathy (non-IgAN) patients through immune receptor sequencing. RESULTS: We identified a significantly higher diversity in the BCR light chain repertoire in IgAN patients compared to non-IgAN patients. Additionally, a higher usage of lambda light chains was observed in IgAN patients. Further network analysis indicated a greater diversification of the BCR lambda light chain repertoire in IgAN patients and identified IgAN-associated lambda light chain clonal lineages with the differentially utilized IGLV gene. CONCLUSION: These findings indicated significantly distinct features of BCR light chain repertoire in IgAN patients and suggested that characteristics of BCR light chain repertoire are very likely as potential biomarkers for the diagnosis of IgAN.