The Best Cut-off Value And Clinical Application Of Serum PLA2R1 Antibody In The Diagnosis Of Idiopathic Membranous Nephropathy

Idiopathic membranous nephropathy(IMN)is one of the major causes of adult nephrotic syndrome.It is a common and frequently-occurring disease in the department of nephrology.The circulating antibody binds to the autoantigen on the surface of the podocyte and forms an immune complex containing the antigen,immunoglobulin and complement under the epithelium.They act on the podocyte to destroy the glomerular filtration barrier and produce the performance of nephrotic syndrome such as proteinuria.Studies have found that M-type phospholipase A2 receptor 1(PLA2R1)is its major target antigen.Anti-PLA2R1 antibodies can be detected in the serum of IMN patients,but the detection rate is quite low in secondary membranous nephropathy(SMN),other nephropathy and healthy people,so the anti-PLA2R1 antibody has an important role in clinical diagnosis and differential diagnosis.The use of enzyme linked immunosorbent assay(Enzyme Linked Immune Sorbent Assay,ELISA)to detect serum anti-PLA2R1 antibodies to diagnose IMN showed high specificity and sensitivity.It has been widely used in clinical work,especially for patients who cannot be diagnosed with renal puncture due to various reasons.In previous studies using ELISA to detect anti-PLA2R1 antibody titer in the diagnosis of idiopathic membranous nephropathy,there were differences in the methods used to select the cutoff value and the specific values determined.However,the difference in cut-off values alone can lead to large differences in sensitivity and specificity.Therefore,it is necessary to determine the cut-off value of the anti-PLA2R1 antibody by ELISA suitable for Chinese people.The correlation study between PLA2R antibodies and clinical indicators has also been actively carried out.Hofstra et al.found that PLA2R antibody levels were positively correlated with proteinuria,serum creatinine,serum β2 microglobulin,and IgG excretion.Xu et al.found that there was no significant difference in clinical indicators(creatinine,albumin,and urine protein filtration rate)between PLA2R-associated IMN and non-PLA2R-associated IMN.Objective:To determine the optimal cut-off value of ELISA for anti-PLA2R1 antibody diagnosis of IMN.The effect of different cutoff values on sensitivity,specificity,positive predictive value,negative predictive value,etc.Observe the relationship between anti-PLA2R1 antibodies and clinical data.METHODS:A total of 119 patients with a definite diagnosis of renal puncture were enrolled.Of these,57 were definitely diagnosed with IMN,62 were with other glomerular diseases,and 17 of them were minimal change glomerulopathy(MCD),focal segmental sclerosis.There were 13 cases of focal glomerulosclerosis(FSGS),8 cases of mesangial proliferative glomerulonephritis(MsPGN),7 cases of IgA nephrosis(IgAN),and proliferative in capillaries.There were 2 cases of endocapillary proliferative glomerulonephritis(EPGN),1 case of mesangiocapillary glomerulonephritis(MPGN),5 cases of diabetic nephropathy(DN),and HBV associated nephritis.There were 3 cases of HBV-N,3 cases of purpura nephritis(PN),2 cases of lupus nephritis(LN)and 1 case of hypertensive renal damage(HRD).In addition,22 healthy examination patients were selected.Collect clinical and biochemical data of renal biopsy at the same time.Serum anti-PLA2R1 antibodies were detected by ELISA.Results:The best cut-off value of ELISA for anti-PLA2R1 antibody diagnosis of IMN was 2.6 RU/ml,its corresponding sensitivity,specificity,positive predictive value was 78.9/91.7/86.5/86.5%,Youden index was 0.706,area under ROC curve.It is 0.879.The sensitivity,specificity,positive predictive value,and negative predictive value of the cutoff value of 2,14,20,40 RU/ml were 82.5/75/69.1/86.3%,59.6/95.2/89.5/77.7%,50.9/96.4/,respectively.90.6/74.3%,and 47.4/97.6/93.1/73.2%.The positive rate of anti-PLA2R1 antibody was 78.9%.There was no statistical difference in clinical data between PLA2R+ and PLA2R-groups(P>0.05).There was no correlation between anti-PLA2R1 antibody titers and clinical data(P>0.05).Conclusion:1.The use of anti-PLA2R1 antibody ELISA method for the diagnosis of IMN has a higher sensitivity and specificity.2.The ELISA method for detection of anti-PLA2R1 antibody against China is the best cut-off value of 2.6Ru/ml.3.There was no statistical difference in clinical parameters between PLA2R+ patients and PLA2R-patients.4.There was no correlation between anti-PLA2R antibody titers and clinical parameters.