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Since the coronavirus disease of 2019 (COVID-19) pandemic swept across the world, the flare of immune-mediated disease following SARS-COV-2 infection has emerged rapidly. Previous studies have documented a growing number of cases of IgA nephropathy (IgAN) subsequent to COVID-19 infection. IgAN has been established as a complement mediated autoimmune disease. Nevertheless, the characteristics of clinical and immunological features in patients with IgAN after COVID-19 infection was scantily reported and merited further exploration.
From December 2022 to April 2023, 33 patients with renal biopsy-proven IgAN (Group A) at Beijing Anzhen hospital who had experienced COVID-19 infection before renal biopsy were enrolled. Meanwhile, 44 patients with IgAN (Group B) diagnosed from December 2018 to April 2019 (the same period in the previous year, with no COVID-19) were enrolled as control. Plasma FHR-5, MBL, C5a, soluble C5b-9, serum Gd-IgA1 and IgA immune complex were detected by enzyme-linked immunosorbent assay. Glomerular staining for FHR-5, C3c, MAC and Gd-IgA1 were detected by immunofluorescence. SARS-COV-2 nucleocapsid and RNA in kidney biopsy was detected by immunohistochemistry. Clinicopathological and immunological features between the two groups were analyzed.
The median time between onset of COVID-19 symptoms and the time of renal biopsy was 12 (6, 18) weeks, ranging from 1 to 26 weeks. 30 (90.9%) had received COVID-19 vaccination before COVID-19 infection. Immunohistochemical investigation for SARS-COV-2 nucleocapsid antigen expression in the renal tubular epithelial cells were observed in 11 (33.3%) patients. Compared with Group B, the level of eGFR was significantly lower in Group A (p=0.010)). Histologically, compared with Group B, patients in IgAN in Group A presented with more percentages of segmental glomerulosclerosis/ adhesion (p=0.003) and less percentages of mesangial hypercellularity (p=0.017). The level of plasma level of C5a (p<0.001), soluble C5b-9 (p=0.018), FHR5 (p<0.001) were significantly higher in Group A compared with Group B, respectively. Even the plasma level of MBL showed no differ in Group A and Group B (p=0.318), we found more patient in Group A presented with high level of MBL than in Group B (p=0.025). Compared with Group B, patients with IgAN in Group A presented with stronger intensity of MAC deposition (p=0.246). There were no significantly different in serum levels of IgA (p=0.129), Gd-IgA1 (p=0.734), IgA immune complex (p=0.524) between Group A and Group B. However, patients with IgAN in Group A exhibited a greater intensity of glomerular Gd-IgA1 deposition in glomerular mesangial and capillary areas than those in Group B (p=0.005).
The activation of the complement system was found to be heightened in individuals diagnosed with IgAN subsequent to a COVID-19 infection. Furthermore, the presence of pathogenic Gd-IgA1 deposits in the glomerular mesangial regions was observed to be more pronounced in IgAN patients with COVID-19 contracted compared to those without. It is plausible that the excessive activation of the complement system and the deposition of pathogenic Gd-IgA1may contribute to the progression of IgAN with COVID-19 infection.