Glomerular Complement Factor H-Related Protein 5 (FHR-5) is Associated with Histological Injury in IgA nephropathy

Abstract Introduction IgA nephrology (IgAN), characterized by co-deposition of IgA and complement components, is an activation of complement system involved disease. Factor H related-5 (FHR-5) antagonized the ability of factor H (FH) to negatively regulate C3 activation, which leads over activation of alternative pathway. Here we explore the relationship of intensity of glomerular FHR-5 deposition and the severity of IgAN. Methods Renal staining of FHR-5 were detected by immunofluorescence, and plasma FHR-5 were detected by enzyme-linked immunosorbent assay in 56 patients with IgAN. The relationship of intensity of glomerular FHR-5 and clinical and pathological features of these patients were further analyzed. Results Glomerular staining for FHR-5 was observed in a predominantly mesangial pattern in 32 (57.1%) biopsies. FHR-5 co-deposited with IgA and C3c in glomerular mesangial and capillary area in patients with IgAN. IgAN patients with Oxford endocapillary hypercellularity (E1) (p=0.007) and segmental glomerulosclerosis (S1) (p = 0.049) presented with more intensity of FHR-5 deposition. There were more cases with 2+ and 3+ FHR5 staining in cohorts of 2+ and 3-4+ mesangial C3 deposition (p = 0.034) and IgA deposition (p = 0.019). Interestingly, the glomerular FHR-5 depositions were more abundant in male versus female in patients with IgAN (p=0.002). Besides, circulating FHR-5 were elevated in IgAN patients compared with healthy control. Plasma FHR-5 levels were significantly higher in patients with mesangial hypercellularity (M1) at diagnosis than those with non-mesangial hypercellularity (M0). Conclusions We found that the glomerular intensity of FHR-5 deposition could indicate the severity of histological lesion of IgAN.