| BackgroundIgA nephropathy(IgAN)is the most common primary glomerulonephritis worldwide and one of the leading causes of end-stage renal disease(ESRD)in China.IgAN patients have different clinical and pathological changes.About 25%-30% of IgAN patients will have renal deterioration after 10 to 20 years of diagnosis,and eventually progress to end-stage renal disease(ESRD),making it a great burden of The public health.Therefore clarifying the pathogenesis of IgAN,and preventing the progression of IgAN is particularly important.Previous studies have confirmed that complement activation is involved in the pathogenesis and progression of IgAN,and complement activation of IgAN is mainly through the alternative pathway and the MBL pathway.Many data have shown that the alternative pathway of complement activation is involved in the development of IgAN,and in recent years researchers have been paying more and more attention to the role and mechanism of complement-activated MBL pathway in the pathogenesis of IgAN.The CLR in the MBL combines with MASP to form a complex that activates the MASPs zymogen,there by activating the MBL pathway.There are three subtypes of MASP1,MASP2 and MASP3 in activated MASP.MASP2 is the main enzyme of MBL pathway.It cleaves C4 and C2 to form C3 convertase,C3 convertase cleaves C3 into C3 a and C3 b,and further forms C5 convertase.Eventually a membrane attack complex is formed,resulting in cell lysis or death.MASP3 is a newly discovered member of the mannose-binding serine protease family in recent years.Studies have shown that it is involved in the activation of factor D,which is a key enzyme for activation during the complement alternative pathway.MASP3 further activates the D factor,thereby promoting the activation of the alternative pathway,further damaging the kidney.At present,many studies have suggested that the MBL pathway is an important pathogenesis of IgAN.Serum MASP2 is a key enzyme for MBL pathway activation.MASP3 is a newly discovered MASPs and is one of the research hotspots of complement activation in recent years.Activation of the complement alternative pathway by activation of factor D is a bridge between activation of the complement pathway and activation of the MBL pathway.The role of serum MASP2 and MASP3 in the pathogenesis of IgAN has not been reported.The purpose of this study was to investigate the relationship between MASP2,MASP3 and IgAN clinical manifestations and pathological changes in serum.To explore the role of MBL pathway in the pathogenesis of IgAN,and provide a reliable basis for the diagnosis and treatment of IgAN.ObjectiveTo investigate the expression of mannose-binding lectin-associated serine proteases 2 and 3(MASP2,MASP3)in the serum of patients with IgA nephropathy(IgAN)and the role in the pathogenesis of IgAN.Methods143 cases of IgAN patients diagnosed by renal biopsy in the Department of Nephrology,the First Affiliated Hospital of Zhengzhou University from September 1st,2016 to March 1st,2017 were collected as the IgAN group,143 healthy subjects from the physical examination department of our hospital were used as a control group.On the day of renal biopsy,3 ml of venous blood was collected and collected through a sterile dry tube.1 ml of centrifugal serum was placed in an EP tube,and stored in a refrigerator at-80 °C for testing.The setum was thawed at 4 °C in the refrigerator.The serum MASP2 and MASP3 concentrations were determined by ELISA.The IgAN group were divided into Q1,Q2,Q3 and Q4 groups by IgAN group serum MASP2,MASP3 concentration value of P25,P50 and P75.To analyze the relationship between serum MASP2,MASP3 concentration and clinical indicators,Oxford pathological score,IgA/C3 immunofluorescence intensity and the prognosis.Results1.There was no significant difference in serum MASP2 concentration between the IgAN group and the control group(P=0.492).The serum MASP3 concentration in the IgAN group was higher than that in the control group(P<0.001).2.The incidence of gross hematuria in low serum MASP2 concentration group(Q1 group)was higher than that in other concentration groups(Q2,Q3,Q4 group)(P<0.05),while 24-hour urine protein content of the high serum MASP2 concentration group(Q4 group)and the proportion of mesangial proliferation in the pathological scores of Oxford and Oxford were higher than that in the other concentrations(Q1,Q2,and Q3 groups)(P<0.05).3.24-hour urine protein content of high Serum MASP3 concentration group(Q4 group)and Oxford pathological score mesangial proliferation ratio,capillary intravascular proliferation ratio,tubular atrophy / interstitial fibrosis ratio,cell / fibrocellular crescent ratio were higher than that in the other concentration groups(Q1,Q2,Q3 group)(P<0.05).4.The serum MASP2 concentration in the weak positive group of IgA fluorescence intensity was higher than that in the strong positive group(P=0.011).There was no significant difference in serum MASP2 and MASP3 concentrations between different C3 fluorescence intensity groups(P>0.05).5.Kaplan-Meier survival curve analysis showed that the renal survival rate of patients with low serum MASP2 concentration group(Q1 group)and high concentration group(Q4 group)was significantly lower than other concentration groups(Q2,Q3 group)(P<0.05),and There was no significant difference in renal survival between the Q1 and Q4 groups(P>0.05).The survival rate of patients with high serum MASP3 concentration group(Q4 group)was significantly lower than that of the other concentration groups(Q1,Q2,Q3 group)(P<0.05).Conclusions1.MASP2 deficiency and MASP2 excess may both have deleterious effects on IgAN progression,which suggests that MASP2 contributes to IgAN pathogenesis through multiple mechanisms.2.Patients with high serum MASP3(>2512.83ng/ml)concentration have more severe proteinuria,and the ratio of mesangial proliferation,intraluminal hyperplasia,tubular atrophy/interstitial fibers proportion and the higher proportion of the crescent appears that high concentrations of MASP3 in the serum contributes to the progression of IgAN. |
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