The Role Of MASP2 And MASP3 In The Pathogenesis Of C3 Glomerulopathy

BackgroundC3 glomerulopathy(C3G)is a type of primary renal disease characterized by immunofluorescence staining of pure complement C3 along glomerular capillary loops.With the deepening understanding of the disease,a new definition of C3 glomerulopathy was defined in the expert consensus of the first C3 glomerular meeting held in August 2012:C3G is mainly C3 deposition glomerulonephritis,immunofluorescence to complement C3 deposits in the(C3 immunofluorescence intensity of fluorescence intensity than other immunoglobulin ≥ ++),and excluding acute streptococcal glomerulonephritis,And other glomerulopathy can be diagnosed before.According to the ultrastructural features,they are divided into two types of diseases.Under dense electron microscope,homogenous drift-like electron-dense deposition occurs in the glomerular basement membrane,but electron-dense deposition under electron microscope fails to meet the DDD standard.When it comes to C3 glomerulonephritis.C3 G is caused by abnormal complement regulation,and complement is activated via the classical pathway,the alternative pathway,and the mannose lectin pathway.Current studies suggest that C3 G is mainly activated by the complement alternative pathway.The role of other complement activation pathways in C3 G is unclear.The MBL pathway is initiated by MBL to recognize the mannose residues of pathogens.By activating MASP2,C4 and C2 are further cleaved to form the MBL pathway C3 convertase(C4bC2a).The C3 convertase cleaves C3 to C3 a and C3 b,further forming C5 convertase(C4bC2aC3b),eventually forming a membrane attack complex(MAC),leading to cell lysis death.Studies have found that C4 cleavage fragment C4 a is significantly higher in plasma of C3 GN patients than in healthy controls,suggesting that C3 G is likely to have MBL pathway activation.MASP3 is a newly discovered mannose-binding serine protease family member in recent years.Recent studies have shown that it is involved in the activation of factor D,and D factor is a key enzyme for activation of the complement alternative pathway.By activating factor D,MAPS3 can be bypassed.Involving in the occurrence of C3 glomerulopathy,MASP3 is a bridge connecting the MBL pathway and the alternative pathway,but whether MASP3 is involved in the pathogenesis of C3 glomerulopathy is currently not reported.This study aimed to investigate the role of MASP2 and MASP3 in the pathogenesis of C3 glomerulopathy by analyzing the correlation between serum MASP2,MASP3 and C3 glomerulopathy patients’ clinical manifestations and pathological changes.ObjectiveTo investigate the expression level of complement mannose-binding serine protease MASP2 and MASP3 in serum of patients with C3 glomerulopathies(C3G)and its role in the pathogenesis of C3 G.MethodsFrom 2012.01.01 to 2017.06.19,we examined 15 patients who were diagnosed with C3 glomerulopathy by renal biopsy and external hospital consultation at the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University.The healthy control group consisted of 10 healthy volunteers who matched the age and sex of C3 glomerulonephritis patients.The EDTA anticoagulated whole blood from the day of renal biopsy was taken and centrifuged at 3000R/min for 5 minutes at4°C.The supernatant was stored in a refrigerator at-80°C until assayed.Serum enzyme-linked immunosorbent assay-sandwich technique(ELISA)was used to determine the levels of MASP2 and MASP3 in each group.The relationship between serum MASP2 and MASP3 levels and changes in clinical indicators and pathologicalgrades was analyzed.ResultsA total of 15 patients with C3 glomerulopathy were included,including 11 males and 4 females with an average age of(43.20±17.55)years.1.Compared with the control group,the levels of serum MASP2 and MASP3 in patients with C3 glomerulopathy were significantly higher(P=0.012 and P=0.001).2.There was no correlation between serum MASP2 level and blood complement C3 level,24-hour urinary protein quantification and serum creatinine in C3 glomerulonephritis patients(P>0.05).There was no correlation between serum MASP3 levels and blood complement C3 and Scr(P>0.05).),but positively correlated with 24-hour urinary protein(r=0.628,P=0.016).3.There was a statistically significant difference between serum MASP2 level and immunofluorescence C3 deposition intensity in C3 G patients(P=0.039),and it was statistically significant(P=0.047)with the presence of electron-dense substances in the basement membrane deposition.ConclusionsThe positive correlation between serum MASP3 and urine protein in patients with C3 G suggests that mannose lectin pathway may be involved in the pathogenesis of C3 G.The abnormal decrease of MASP2 level may be related to the worsening of pathological damage of C3 glomerulopathy...