Expression And Significance Of Phospholipase A2 Receptor And Platelet 7A Domain Protein In Patients With Membranous Nephropathy

[Research Background]Membranous nephropathy is the most common primary glomerular disease in adult nephrotic syndrome.Its typical pathological feature is the formation of primary immune complexes in the subepithelial space above the glomerular basement membrane.Membranous nephropathy mainly includes two types,namely primary membranous nephropathy and secondary membranous nephropathy.There is no obvious difference in pathological manifestations between these two types of membranous nephropathy,which is mainly identified by finding relevant secondary factors in clinical practice.In recent years,the statistics of renal biopsy in the world showed that the proportion of primary membranous nephropathy in primary glomerular disease was significantly higher than in previous years,and the incidence rate was increasing.Previous diagnosis of membranous nephropathy mainly through joint renal biopsy to exclude secondary factors,but many patients are not suitable for biopsy in the actual process,such as congenital solitary kidney,small kidney,patients with severe hypertension and significant bleeding tendency.Therefore,it is extremely important to find a serum marker to assist in the diagnosis of primary membranous nephropathy and to guide the patient's condition and treatment plan.In 2009,Beck et al found in the Western blot confirmed by renal biopsy serum idiopathic membranous nephropathy in a length of about 185kd protein,and the protein is expressed only in the length of membranous nephropathy,not in the following expression membranous nephritis and other types of primary glomerular nephropathy,and confirmed by a recombinant PLA2R(phospholipase A2 receptor)which is an anti-protein antibody-PLA2R the expression properties,is proposed to differentiate primary PLA2R The main marker of secondary membranous nephropathy.In 2014,Tomas et al proposed platelet 7A domain protein in primary glomerular podocytes surface,and antibody positive serum anti THSD7A,membranous nephropathy is associated THSD7A Since podocytes surface situ immune complex formation.Studies have confirmed that serum detection of PLA2R antibody positive diagnostic membranous nephropathy accounts for 52-70%of patients with primary membranous nephropathy.Serum THSD7A antibodies are mainly present in serum-PLA2R antibody-negative patients.Therefore,patients with primary membranous nephropathy with anti-PLA2R-negative disease can be diagnosed by detecting serum THSD7A antibodies.About 2-9%of patients with serum THSD7A antibody-positive membranous nephropathy.Therefore,the combination of the two to detect the serum of patients further increases the accuracy of the diagnosis of primary membranous nephropathy.However,with the continuous deepening of research,people gradually found that PLA2R-associated membranous nephropathy and THSD7A-associated membranous nephropathy were different in patients in different regions and in different ethnic groups.It was found that there were two antibodies in the serum of the same patient,and there were two antigens on the surface of glomerular podocytes.Purpose of this study is to explore the present positive anti-PLA2R antibody and anti-centerTHSD7A expressing both antibody and antigen expression on glomerular podocytes surface where the membranous nephropathy;Discussion antibody,antigen concentration and the presence or absence of significant clinical covariatesAssociations.[Research methods]Serum(including primary and secondary)of patients diagnosed as membranous nephropathy(n=232)diagnosed by renal biopsy from Qilu Hospital of Shandong University from 2013 to 2017 was collected,and relevant clinical data including patient ages were collected.,Sex,Total urinary protein,renal tubular function,serum complement C3,C4,ESR,serum total protein,albumin,LDL,cholesterol,alanine aminotransferase,aspartate aminotransferase,serum creatinine,urea nitrogen,glomerular filtration Overage,hemoglobin,red blood cell count.Enzyme-linked immunosorbent assay(ELISA)was performed on the patient's serum to determine the concentration of anti-PLA2R antibodies and anti-THSD7A antibodies in the serum.Seventy-five patients were immunohistochemically stained for renal tissue to determine whether PLA2R and THSD7A antigen-antibody complex deposition occurred on the surface of glomerular podocytes.[result]1.The positive rate of anti-PLA2R antibody in serum and renal tissue of patients with primary membranous nephropathy is greater than that of anti-THSD7A.There were 46 double-positive patients in the serum.2.Serum anti-THSD7A antibody had no significant correlation with age,serum anti-PLA2R antibody was negatively correlated with age.3.Serum anti-PLA2R antibody and serum anti-THSD7A antibody were positively correlated with total urine protein and urinary albumin,but were not significantly correlated with other clinical indicators.4.Serum anti-PLA2R antibody positive group and negative group showed significant differences in age,red blood cell count,alanine aminotransferase,urinary albumin index.Anti-THSD7A antibody positive group and negative group had significant differences in age,alanine aminotransferase,aspartate aminotransferase,and urinary albumin.5.serum PLA2R antibody diagnosis of idiopathic membranous nephropathy sensitivity was 61.05%,specificity was 40.9%,serum anti-THSD7A diagnosis of idiopathic membranous nephropathy sensitivity was 27.3%,a specificity of 54.5%.The sensitivity of the renal tissue PLA2R antigen staining for the diagnosis of idiopathic membranous nephropathy was 77.27%with a specificity of 66.7%.The sensitivity of renal tissue THSD7A antigen staining for the diagnosis of idiopathic membranous nephropathy was 6.7%with a specificity of 83.3%.6.The positive rate of PLA2R antigen staining in renal tissue was 78.5%,and 2 antigens were positive in secondary membranous nephropathy.The positive rate of THSD7A antigen staining was 7.7%in primary membranous nephropathy,and positive in one case of secondary membranous nephropathy.[Conclusion]The positive rate of anti-PLA2R antibody in serum was significantly lower than that of renal tissue antigen detection.The specificity of THSD7A in the renal tissue for the diagnosis of membranous nephropathy is high,serum antibody detection and renal tissue antigen detection have their advantages and limitations,combined with serum and kidney tissue is the best method.There is a certain relationship between blood antibody concentration and clinical indicators,which can be used as a basis for assessing disease activity or drug sensitivity.