The Role Of Complement C3a,C5a And Their Receptors In The Pathogenesis Of IgA Nephropathy

Backgroud and ObjectiveIgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide and leads to renal failure in a substantial number of patients. Recent studies have suggested that complement activation may play a part in the inflammatory injury process in IgAN. Complement activation products C3a and C5a have broad pro-inflammatory potential and contribute to the pathogenesis of several inflammatory and autoimmune diseases. However, their roles in IgAN are not well-defined. In this study, we investigated the role of C3a, C5a and their receptors in the pathogenesis of IgA nephropathy.MethodsEighty-three IgAN patients proved by renal biopsy were investigated,30patients as Lee’s Ⅱ,30as Lee’s Ⅲ,23as Lee’s Ⅳ, meanwhile10cases of normal renal tissue from nephrectomy patients with kidney tumor were selected as controls. Immunhistochemistry of TNF-a and IL-6were performed to measure the pro-inflammatory mediators expression in the kidney tissue. The deposition of C3a and C5a was assessed using immunohistochemical staining. The expressions of C3aR and C5aR in renal tissue were detected respectively using immunohistochemical staining. These83IgA nephropathy patients’serum and urine samples were collected, meanwhile10healthy volunteers’as normal controls, and10sepsis patients’ as positive controls. C3a and C5a levels in serum and urine in each group were detected respectively using ELIS A.Results(1) The deposition of C3a,C5a in renal tissue in IgAN increased with the degree of kidney pathological injury (P<0.05). Moreover, the deposition of C3a,C5a were proportional to the expression of TNF-a and IL-6(P<0.05).(2) Along with the increasing pathological injury levels, C3aR and C5aR expressed enhanced in renal tissue of IgAN patients. Furthermore, the expression had a positive correlation with the expression of TNF-a and IL-6(P<0.05).(3)The levels of serous and urinary C3a,C5a were significantly higher in those IgAN and sepsis patients than those healthy volunteers. Furthermore, the levels of urinary C3a,C5a in those IgAN patients were proportional to the degree of kidney pathological injury (P<0.05). However, it showed no significant difference between IgAN and sepsis patients (P>0.05).Conclusions(1) C3a and C5a play an important role in renal pathological injury and evidently contributes to the pathogenisis and progression of IgAN.(2) C3a, C5a may promote the inflammatory response to induce the development of IgA nephropathy.