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Glomerular Complement Factor H-Related Protein 5 is Associated with Histologic Injury in Immunoglobulin A Nephropathy
Wei-Yi Guo1, Li-Jun Sun1, Hong-Rui Dong1
1Renal Division, Department of Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Introduction:
Immunoglobulin A nephrology (IgAN), characterized by co-deposition of IgA and complement components, is an activation of complement system involved disease. Factor H-related protein 5 (FHR-5) antagonized the ability of factor H to negatively regulate C3 activation, which leads to overactivation of the alternative pathway. Here we explore the relationship of intensity of glomerular FHR-5 deposition and severity of IgAN.
Methods:
Renal staining of FHR-5 was detected by immunofluorescence, and plasma FHR-5 was detected by enzyme-linked immunosorbent assay in 56 patients with IgAN. The relationship of intensity of glomerular FHR-5 and clinical and pathologic features of these patients were further analyzed.
Results:
Glomerular staining for FHR-5 was observed in a predominantly mesangial pattern in 32 biopsy specimens (57.1%). FHR-5 co-deposited with IgA and C3c in glomerular mesangial and capillary area in patients with IgAN. Patients with IgAN with Oxford endocapillary hypercellularity (P = 0.007) and segmental glomerulosclerosis (P = 0.049) presented with greater intensity of FHR-5 deposition. There were more cases with 2+ and 3+ FHR-5 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 levels were elevated in patients with IgAN compared with healthy control subjects. Plasma FHR-5 levels were significantly higher in patients with mesangial hypercellularity at diagnosis than those with nonmesangial hypercellularity.
Conclusions:
We found that glomerular intensity of FHR-5 deposition could indicate the severity of histologic lesions of IgAN.
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