Evaluation Of Anti-PLA2R Antibodies Combined With Complement Lectin Pathway-related Markers In The Diagnosis Of Idiopathic Membranous Nephropathy

Objective: The objective of the study is to investigate the level of MBL,MASP-1,MASP-2 and C5b-9 in serum of IMN patients and healthy controls,to discuss the differences of the levels between IMN patients and healthy controls and to infer the function of complement lectin pathway in the pathogenesis of IMN.In addition,the study was aimed to detect the level of significant indicators of healthy controls and IMN patients in the serum of non-IMN nephropathy patients,detect the level of anti-PLA2 R antibodies in IMN patients and non-IMN nephropathy patients and evaluate the diagnostic efficacy of the joint detection of different indicators by drawing receiver operating characteristic curve.Methods: 144 IMN patients were enrolled from Shengjing Hospital of China Medical University,who were diagnosed IMN by renal biopsy.They were diagnosed as IMN the first time and haven't been treated.38 age-and gender-matched healthy individuals and 40 age-and gender-matched other nephropathy cases(non-idiopathic membranous nephropathy)were recruited from Shengjing Hospital of China Medical University.The serum concentrations of MBL,MASP-1,MASP-2,C5b-9 and anti-PLA2 R antibodies were determined by enzyme-linked immunosorbent assay.The IMN patients were divided into two groups,PLA2 R positive group and PLA2 R negative group by the qualitative analysis of anti-PLA2 R antibody.The concentration differences in serum of MBL,MASP-1,MASP-2 and C5b-9 between IMN group and health control group and the differences of these four biomarkers between PLA2 R positive group and PLA2 R negative group were analyzed.According to the test results,the serum levels of MASP-1,MASP-2 and anti-PLA2 R antibodies in 40 non-IMN nephropathy patients were measured.ROC curves were drawn to evaluate the diagnostic efficacy of two indicators joint detection and three indicators joint detection.Results: 1.The concentration of MBL,MASP-1,MASP-2 and C5b-9 in IMN group is 8.83(5.84-15.72)?g/mL,2903.95(1917.81-3339.71)ng/mL,133.38(79.21-170.37)ng/mL and 235.94(198.44-264.70)ng/mL,which is 10.34(6.12-14.27)?g/mL,1486.50(1082.15-1939.86)ng/mL,247.10(184.03-312.02)ng/mL and 227.58(194.69-364.78)ng/ mL in healthy control group.Compared to healthy control group,the level of serum MASP-1 is significantly higher in IMN group(P<0.001),while the level of serum MASP-2 is lower in IMN group(P<0.001).The level of serum MBL and C5b-9 showed no statistical differences.2.The concentration of MBL,MASP-1,MASP-2 and C5b-9 in PLA2 R positive group was 8.70(5.61-15.36)?g/mL,2815.14(1857.70-3342.26)ng/mL,131.34(75.07-170.25)ng/mL and 230.77(190.53-266.61)ng/mL respectively.The concentration of these four biomarkers in PLA2 R negative group is 10.51(5.96-16.45)?g/mL,3102.84(1997.94-3339.12)ng/mL and 146.92(99.18-170.44)ng/mL and 243.77(231.06-264.40)ng/mL.The four biomarkers of the complement lectin pathway showed no difference between PLA2 R positive group and PLA2 R negative group.3.The serum protein level and serum albumin level are lower statistically in PLA2 R positive group than in PLA2 R negative group.The 24 hour urine protein level and urine red blood cell count are higher in PLA2 R positive group statistically.4.The area under the ROC curve of MASP-1,MASP-2 and anti-PLA2 R antibodies combined detection was 0.953.The area under the ROC curve of MASP-1 and anti-PLA2 R antibodies combined detection was 0.939.The area under the ROC curve of MASP-2 and anti-PLA2 R antibodies combined detection was 0.943.The AUC of the detection of anti-PLA2 R antibodies combined with MASP-1 or MASP-2 and the combination of MASP-1,MASP-2 and anti-PLA2 R antibodies are statistically larger than the AUC of anti-Pl A2 R antibodies detecting alone(P<0.001).Conclusion: Serum levels of anti-PLA2 R antibodies in patients with idiopathic membranous nephropathy correlate with disease status.The serum levels of MASP-1 and MASP-2,the key factors of the complement lectin pathway,showed significant differences between IMN patients and healthy controls.Complement lectin pathway activation may be involved in the pathogenesis of idiopathic membranous nephropathy.The combined detection of MASP-1,MASP-2 and anti-PLA2 R antibodies and the detection of anti-PLA2 R antibodies combined with MASP-1 or MASP-2 can improve the diagnostic efficacy of idiopathic membranous nephropathy compared with anti-PLA2 R antibodies detection alone.