Background: Membranous nephropathy (MN) is characterized by subepithelial immune complex deposits of IgG, particularly anti-Phospholipase A2 Receptor (anti-Pla2r). However, presence of IgA co-deposition along subepithelial region of the glomerular capillary walls has not been extensively investigated.
Methods: Five hundred thirty-one biopsy-proven MN patients from Huashan Hospital were screened for capillary IgA deposition. Clinical, biological and histopathological data were collected at biopsy and during follow-ups. A propensity score matched cohort was used to compare treatment response and outcomes between MN patients with capillary co-deposition of IgG and IgA (cIgA-MN) and MN without. Immunofluorescence was used to detect IgA, IgG, Galactose deficient-IgA1 (Gd-IgA1) and Pla2r deposition. ELISA was performed to measure circulating Gd-IgA1 level. IgA and IgG subtypes of sera anti-Pla2r antibodies were investigated by indirect immunofluorescence and validated by ELISA.
Results: Fifty-three of 531 MN patients exhibited capillary IgA co-deposition with IgG. Secondary causes were identified in 19 of 53 cIgA-MN patients. The remaining 34 primary cIgA-MN patients had median proteinuria of 6.1 g/day and showed no crescents and mild endocapillary proliferation. 73.5% cIgA-MN patients were positive for Pla2r. Gd-IgA1 was absent in glomeruli of cIgA-MN patients and circulating Gd-IgA1 levels were similar to those in MN patients without IgA deposition. Meanwhile, circulating IgA-type anti-Pla2r antibodies were detected in a subset of cIgA-MN patients. Outcome analysis revealed comparable remission rates and progression to end-stage kideny disease between cIgA-MN and MN without IgA deposition.
Conclusion: This study highlights clinical and pathological features of cIgA-MN, suggesting complex immune responses involving IgA in MN. IgA co-deposition did not significantly alter treatment responses or long-term outcomes.
Keywords: IgA; IgG; Membranous nephropathy; capillary co-deposition.