血清MASP2、MASP3在IgA肾病中的作用

Role of serum MASP2 and MASP3 in IgA nephropathy

目的:研究血清甘露糖结合凝集素相关丝氨酸蛋白酶2、3(MASP2、MASP3)在IgA肾病(IgAN)患者血清中的表达及其在IgAN发病中的作用。方法:收集我院2016年9月至2017年3月首次经肾活检确诊的143例IgAN患者作为病例组,同期在我院体检科的60例健康体检者作为对照组。用ELISA方法测定血清MASP2、MASP3浓度,分析血清MASP2、MASP3浓度与各临床指标、牛津病理评分、IgA/C3免疫荧光沉积强度以及预后的关系。结果:(1)IgAN组与对照组血清MASP2浓度无统计学差异(Z=-0.347,P=0.729),IgAN组血清MASP3浓度高于对照组(Z=-3.8,P<0.001)。(2)与血清中等浓度MASP2(224.22,2540.50 ng/ml)的IgAN患者相比,血清低浓度MASP2(<224.22 ng/ml)患者肉眼血尿发生率更高(χ2=9.892,P=0.002),而血清高浓度MASP2(>2540.50 ng/ml)患者有更严重的蛋白尿(Z=-2.64,P=0.008)和更高的新月体评分(χ2=5.165,P=0.023)。(3)与血清低中量浓度MASP3(≤2512.83 ng/ml)的IgAN患者相比,血清高浓度MASP3(>2512.83 ng/ml)患者有更严重的蛋白尿(Z=-4.526,P<0.001),且系膜增生比例、毛细血管内增生比例、肾小管萎缩/间质纤维化比例、新月体比例较高(χ2=8.955,P=0.003;χ2=4.484,P=0.034;χ2=9.853,P=0.002;χ2=9.516,P=0.002)。(4)IgA荧光强度弱阳性组血清MASP2浓度高于强阳性组(Z=-2.546,P=0.011),不同C3荧光强度血清MASP2、MASP3浓度间差异均无统计学意义(P>0.05)。(5)Kaplan-Meier生存曲线显示血清MASP2低浓度组和高浓度组患者肾脏生存率明显低于中等浓度组(P<0.05)。血清高MASP3浓度组患者肾脏生存率明显低于低中量浓度组(P<0.05)。结论:(1)血清中过高或过低浓度的MASP2在IgAN的发展中均起作用,MASP2可能在IgAN中具有多重作用机制。(2)血清中高浓度的MASP3可能促进了IgAN的进展。

Objective:To 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 its role in the pathogenesis of IgAN.Methods:A total of 143 patients with IgA nephropathy(IgAN)diagnosed by renal biopsy from September 2016 to March 2017 were enrolled as case groups.Sixty healthy volunteers in the physical exa mination of our hospital were seclected as a control group.The levels of serum mannose-binding lectin-associated serine proteases 2 and 3(MASP2,MASP3)in each group were detected by ELISA.The differences of serum MASP2 and MASP3 concentrations between the case group and the control group were compared,and the relationship of serum MASP2,MASP3 concentration with clinical features,Oxford pathological scores,IgA/C3 fluorescence intensity and prognosis were analyzed.Results:(1)There was no significant difference in serum MASP2 concentration between IgAN group and control group(Z=-0.347,P=0.729).The serum MASP3 concentration in IgAN group was higher than that in the control group(Z=-3.8,P<0.001).(2)Compared with moderate serum MASP2(224.22,2540.50 ng/ml)of IgAN patients,IgAN patients with low serum MASP2(<224.22 ng/ml)had a higher incidence of gross hematuria(χ2=9.892,P=0.002),and IgAN patients with high serum MASP2(>2540.50 ng/ml)had more severe proteinuria(Z=-2.64,P=0.008)and a higher crescent score(χ2=5.165,P=0.023).(3)Compared with low and moderate concentration serum MASP3(≤2512.83 ng/ml)of IgAN patients,IgAN patients with high serum MASP3(>2512.83 ng/ml)had more severe proteinuria(Z=-4.526,P<0.001),and the proportion of mesangial hypercellularity,the proportion of endocapillary cellularity,the proportion of interstitial fibrosis/tubular atrophy,and the proportion of cell/fibrocytic crescents were higher(χ2=8.955,P=0.003;χ2=4.484,P=0.034;χ2=9.853,P=0.002;χ2=9.516,P=0.002).(4)The serum MASP2 concentration in the weakly positive group of IgA fluorescence intensity was higher than the strongly positive group(Z=-2.546,P=0.011).There was no significant difference of serum MASP2 and MASP3 concentrations between different C3 fluorescence intensity groups(P>0.05).(5)Kaplan-Meier survival curves showed that the renal survival rate was significantly lower in patients with serum MASP2 low concentration group and high concentration group than that in patients with moderate concentration group(P<0.05),and the renal survival rate was significantly lower in patients with serum MASP3 high concentration group than that in patients with low and moderate concentration(P<0.05).Conclusion:(1)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)The high concentrations of MASP3 in serum may contribute to the progression of IgAN.