Objective:Membranous nephropathy(MN)is the most common pathological type of nephrotic syndrome in adults,and its mechanism is complex and unclear.About one-third of MN patients develop into end stage renal disease(ESRD)with severe complications.At present,the gold standard for the diagnosis of MN is still renal puncture biopsy,and the invasive operation is not conducive to repeated detection.Exploring potential MN target antigens with sensitivity,specificity and noninvasiveness has become an important research field.Anti-phospholipase A2 receptor(PLA2R)and thrombospondin type 1 domain containing7A(THSD7A)has been proved to be a biomarker of MN,accounting for 70-80% and1-5% of primary MN,respectively.However,the research data are mostly based on populations in Europe and North America,and the serological expression and clinical characteristics of Th SD7 A are rarely reported in China.In recent years,exostosin1/exostosin 2(EXT1/EXT2),semaphorin 3B(Sema-3B)and neural epidermal growth faction-like 1 protein(NELL-1)were proposed as potential markers of MN.The positive rate of these markers in kidney tissue was very low,and there were few relevant reports in China.Serological antibody expression is even less clear.In this study,serum anti-PLA2 R and THSD7 A antibodies were detected in MN patients,and expression concentrations of EXT1/EXT2,Sema-3B and NELL-1 were detected in MN patients with double negative PLA2R/THSD7 A,so as to provide clinical data for the disease characteristics of MN in China.Methods:1.372 patients pathologically diagnosed with membranous nephropathy were included,blood samples were collected,baseline information,complications,kidney puncture pathology results,drug use,laboratory test results,serum PLA2 R antibody concentration,THSD7 A antibody concentration and other information were collected,and statistical analysis was performed using R language(4.2.0),with a test level of α=0.05.2.Thirty patients with membranous nephropathy with negative expression of PLA2 R and THSD7 A were included in the study.Baseline information and laboratory test results were collected,and serum concentrations of EXT1,EXT2,Sema-3B and NELL-1antibodies were detected by quantitative kit(double-antibody one-step sandwich enzyme-linked immunosorbent assay)for correlation analysis.The statistics part is the same as 1.Results:1.Among 372 patients with membranous nephropathy,243(65.32%)were males and129(34.68%)were females;The mean age of onset was 31.68 ± 12.27 years old(16-77 years old).There were 45(12.1%),262(70.43%)and 39(10.49%)patients with membranous nephropathy in stage Ⅰ,Ⅱ and Ⅲ,respectively.The positive rate of PLA2 R was 88.62% in pathology and 68.3% in serum.35.75% of the patients had hypertension,followed by diabetes(11.56%).Patients with membranous nephropathy had low blood albumin,immunoglobulin Igk and k/λ,high total cholesterol,triglyceride,low density lipoprotein and 24 h urinary protein.In correlation analysis,serum PLA2 R concentration was positively correlated with 24 h urinary protein,complement C4,low density lipoprotein,triglyceride,cystatin C,serum creatinine and erythrocyte sedimentation rate.Serum PLA2 R concentration was negatively correlated with MPO,Igk,Igλ,Ig G,glomerular filtration rate,total protein,albumin and erythrocyte count,and the differences were statistically significant(P<0.05);The e positive rate of serum THSD7 A in patients with membranous nephropathy was 0.27%.2.Women accounted for 60% of the patients with double negative serum PLA2R/THSD7 A membranous nephropathy;the average age of onset of double negative patients was 41.43 ± 11.97 years old;the number of patients with double negative membranous nephropathy decreased gradually with the increase of pathological stage;10%of double negative patients were complicated with hypertension.The prevalence of diabetes mellitus,hepatitis B virus infection or rheumatic diseases was 6.67%,respectively.Patients with double negative membranous nephropathy had lower blood albumin index,higher total cholesterol,triglyceride,low density lipoprotein and 24 h urinary protein,and positive rates of MPO,PR3 and GBM were 20%,10% and 10%,respectively.Other laboratory indicators are roughly within the normal reference range.Correlation analysis showed that serum SEMA-3B concentration was positively correlated with hepatitis B virus infection.Serum NELL-1 concentration was positively correlated with triglyceride,hepatitis B virus infection,leukocyte count and neutrophil count.Serum EXT1 concentration was positively correlated with Ig M and negatively correlated with age.Serum EXT2 concentration was positively correlated with white blood cell count,neutrophil count,lymphocyte count and triglyceride,and negatively correlated with Ig G level,with statistically significant differences(P<0.05).Conclusion:1.The positive rate of PLA2 R kidney tissue in MN patients was higher than serological positive rate,and patients with pathological/serological PLA2 R expression double positive may have worse abnormal test indexes such as blood lipid and 24 h urine protein.2.Serum anti-PLA2 R antibody concentration has significant differences in MN pathological staging,and is significantly correlated with clinical indicators such as renal function and blood lipid.Clinical outcome of MN patients can be predicted and early diagnosis can be made by monitoring PLA2 R antibody concentration.3.In this study,372 MN patients were tested for serum THSD7 A antibody.As far as we know,this is the largest number of serum THSD7 A antibody studies in China at present,and the positive rate is only 0.27%,which is not consistent with the incidence rate of 1-5%in foreign countries,which may be related to regional differences.4.Serum expressions of NELL-1,EXT1,EXT2 and Sema-3B in PLA2R/THSD7 A double-negative MN patients had no significant correlation with MN pathological stage,serum creatinine,urea nitrogen,24 h urinary protein and other indicators closely related to the development of kidney disease.However,due to the small sample size,it is necessary to expand the sample size for further studies on whether these indicators can reflect MN activity and prognosis. |