The Significance Of IgG4and Complement Factor â…  In Idiopathic Membranous Nephropathy

Objectives：Membranous nephropathy（MN）is a common pathologicaltype of nephrotic syndrome in adults. The disease is characterized by thepresence of immune complexes in the subepithelial space of the glomerularfiltration barrier. The etiology of idiopathic membranous nephropathy (IMN)is unknown. According to the relevant reports, the incidence of IMN in ourcountry accounts for9.9%~13.5%in primary glomerular disease. Therefore,we should explore effective indicators of IMN actively. It is important toprevent IMN progressing to end-stage renal disease.The pathogenesis of IMN is that IgG and the inherent antigen ofglomerular podocyte form the antigen-antibody complexes and activate thecomplement system. Membrane attack complex (MAC, C5b-9) causesmorphological changes of podocytes, proteinuria and hypoalbuminemia. IgG4is the mainly subclass depositing on the podpcytes. The deposit position ofpathogenic antigens newly discovered is the same as IgG4in the glomerulus.The complement system is the most important regulator of glomerular injurymechanism in MN. The complement activation of IMN is mainly throughalternative pathway, and influenced by contributing factor (immune complex)and inhibiting factor (complement regulatory proteins). Complementregulating factor Ⅰ, also called complement I factor (CFI), expresses in livercells, mononuclear cells, fibroblasts, keratinocytes and so on. CFI is animportant complement regulatory protein in alternative pathway. CFI cancrack C3b, inhibit complement activation and reduce podocytes damagecaused by MAC.By means of biochemical indicator measurement orimmunohistochemistry assay, we analyze the expression of IgG subclasses,CFI and C3b in IMN and minimal change nephropathy (MCD) renal tissue, also analyze the concentration level of IgG4, CFI and C3b in blood, urinethrough the method of double antibody sandwich enzyme-linkedimmunosorbent assay (ELISA method). We clarify the relationship betweenIgG4, CFI and C3b, and the significance of CFI in IMN complementactivation regulating mechanism further.Methods：The patients with IMN referred to the Third Hospital of HebeiMedical University in2013were studied. Diagnosis was made by lightmicroscopic, immunofluorescence and electron microscopic examination ofrenal biopsies. The IMN group was named as groupⅠ, and the MCD groupwas named as group II. Renal biopsy specimens were sliced by paraffinembedding. The IgG subclasses were divided into IgG4positive group (groupⅠ a) and IgG4negative group (group Ⅰ b) by means ofimmunohistochemistry assay. At the same time we detected the sedimentarycharacteristics of CFI, C3b, IgG1and IgG4in renal tissues. Theimmunohistochemistry results were analyzed through Image-Pro Plus (PPI)system. Meanwhile, we collected blood and urine specimens on the renalbiopsy day of the patients in groupⅠand groupⅡ, we detected CFI,C3b,IgG4and IgG levels by means of quantitative ELISA method, and measuredthe ratio between IgG4/IgG in every group. Measurement data of normaldistribution are expressed as thex±S. Measurement data of skewnessdistribution are expressed as the median (mix-max). Statistical comparisons ofnormal distribution data were made using two independent sample t-test andanalysis of variance. Statistical comparisons of skewness distribution datawere made using the Mann-Whitney U test. All the data were analyzed bySPSS17.0system, and P＜0.05was considered to have statistical significance.Results: Kidney immunohistochemistry displayed that both CFI and C3bhad expressed in IgG4positive group of IMN group than IgG4negative groupand MCD group (P <0.05); IgG1had little expressed in IMN group; ELISAshowed blood、urine IgG4/IgG ratio, factor Ⅰ, and C3b of IMN group werehigher than MCD group(P <0.05).Conclusion: The mainly IgG subclasses of antigen-antibody immune complexes in renal epithelium of IMN and in the blood is IgG4.The increasedlevel of C3b in blood and urine is the indicator in complement activation ofIMN. The CFI promotes the degradation of C3b that is the key enzyme incomplement activation alternative pathway of IMN. The CFI also inhibitscomplement activation, and plays an important role in regulating complementactivation and preventing renal damage.