| Objective:Membranous nephropathy（MN）is one of the most common pathological types of adult nephrotic syndrome.Idiopathic membranous nephropathy（IMN）accounts for about 75 percent of MN.M type phospholipase A2 receptor（PLA2R）was already identified as a specific target antigen of IMN.However,a small number of patients had negative expression of PLA2R.It means that other antigens might be involved in the pathogenesis of MN.The thrombospondin-type 1 domain containing 7A（THSD7A）was reported to be an another pathogenic antigen of IMN in 2014.THSD7A was also demonstrated to be related to malignant tumors,and the incidence of tumor in THSD7A positive IMN patients was much higher than that in the negative group.At present,there are few studies on THSD7A in China.THSD7A was detected in renal biopsy tissue of patients with IMN,and the clinical characteristics of these patients were analyzed.We also concerned about the occurrence of malignant tumors in THSD7A-positive patients.Method:1.Patients with biopsy-proved MN in Nephrology Department of Sichuan Provincial People’s Hospital were enrolled from January 2016 to September 2017,and total 110 cases with IMN patients,5 cases with hepatitis B virus associated membranous nephropathy,as well as 15 cases with type V lupus nephritis were included in the study.And 10 cases with minimal change nephropathy served as controls.2.All the renal tissue specimens were collectedandtheexpressionofTHSD7Awasdetectedby immune-histochemical staining.The serum samples of these patients were collected to detect the expression of anti-THSD7A antibody and anti-PLA2R antibody in serum by Enzyme linked immunosorbent assay.3.The clinical data,including laboratory testing,treatment,outcomes and tumor occurrence,were collected for further analysis.Results:1.The age of MCD patients was younger than IMN group and SMN group(P1=1.68×10-4,P2=0.033).The gender composition of SMN group was different from IMN and MCD group（P1=0.013,P2=0.002）.2、The serum albumin level in MCD group was 18.61±??g/l,which was significantly lower than that in IMN and MCD group（P1=0.002,P2=0.004）;The hemoglobin level in the SMN group was lower than that in the MCD group（P=0.001）;the cholesterol level among three groups were different,and the difference was statistically significant(P1=1.32×10-8,P2=0.003,P3=1.02×10-5).The level of IgG in SMN patients was higher than that in IMN and MCD patients(P1=1.227×10-5,P2=1.84×10-4).The levels of C3 in patients with SMN were significantly lower than those of IMN and MCD(P1=1.29×10-5,P2=0.018).3.A total of 4patients with THSD7A positive were detected,and they all were IMN patients.The positive rate was 3.63%in IMN group.The four cases of THSD7A positive renal pathology showed dark brown substance distributed granular or linear along capillary loops and basal membrane,and no expression was found in tissues other than glomeruli.4.There were four THSD7A-positive IMN patients,including 2 female patients and two male patients.The 4 patients were mainly characterized by proteinuria and edema.Except the serum lipid profile,there weren’t significant differences of the clinical characteristics of the patients with or without THSD7A positive.5.In this study,the serum PLA2R antibodies were detected in 72 patients.The positive rate was 65.45%.In the SMN group,2 patients had anti-PLA2R-Ab positive（10%）.No patient in MCD group had serum anti-PLA2R-Ab positive,and the difference of the positive rate was statistically significant among the three groups(P=8.05×10-10).The 4 THSD7A-positive patients were negative for serum anti-PLA2R-Ab.In terms of clinical manifestations,serum creatinine,serum albumin and IgG levels of PLA2R positive patients were higher than those of anti-PLA2R-Ab negative patients.The difference was statistically significant（P1=0.019,P2=0.029,P3=0.034）.6 Follow up:4 THSD7A positive patients all found the tumor markers increased,the follow-up time was（7.25+1.5）months,1 cases of partial remission,2 cases were not relieved,1 cases were missed while following-up.The tumor has not yet been found in the three patients.Conclusion:1.The majority of the patients with IMN were middle-aged men.and proteinuria is the main clinical feature.The characteristics of nephrotic syndrome in SMN patients were not prominent.2.The positive expression of THSD7A in the renal tissue was linear or granulation along the capillary loop of the capillary loop.The positive rate of THSD7A in IMN was 3.63%.3.the positive rate of Anti-PLA2R-Ab in IMN was 64.45%.4.Combined detection of THSD7A and PLA2R could improve the diagnostic rate of IMN.5.THSD7A positive IMN patients might have poorer response to immunosuppressive therapy. |
