To Investigate The Clinical Value Of Anti-PLA2R Antibody In The Treatment Of Idiopathic Membranous Nephropathy

Background:Idiopathic Membranous Nephropathy(IMN)is a common cause of nephrotic syndrome in adults.There are three main outcomes of IMN:(1)spontaneous remission;(2)Intractable proteinuria but renal function remained stable;(3)Intractable proteinuria with renal failure.Currently,urinary protein and renal function are generally used as the main indexes for treatment.However,these indexes cannot accurately reflect IMN immune activity,which may lead to unreasonable treatment.In 2009,Beck reported that the M-type phospholipase A2 receptor(PLA2R)and serum anti-PLA2R antibody were the main target antigens and antibodies of IMN,which was a breakthrough understanding of the pathogenesis of IMN.Subsequent studies have confirmed the diagnostic value of antibodies in IMN,but there is still no consensus on how to better use of PLA2R antibody to evaluate disease activity,to guide treatment and to judge prognosis,and still need more clinical observations to confirmed these theory.Objective: Through prospective detection the baseline serum anti PLA2R antibodies in the patients with IMN and follow-up of its dynamic change,to analyze the correlation between anti-PLA2R antibody and clinical parameters,such as between the antibody and IMN disease remission,and prognosis of IMN patients treated immunosuppressive,and to explore the clinical significance and application value of anti-PLA2R antibody in the treatment of IMN,and to provide clinical practice basis for disease assessment,accurate treatment and prognosis prediction of membranous nephropathy.METHODS: Patients with IMN treated in the Nephrology Department in No.924 Hospital of the People’s Liberation Army Joint Logistic Support Force from January 2019 to June 2020 were collected.All the patients were pathological diagnosis membranous nephropathy by renal biopsy under local anesthesia,and the secondary membranous nephropathy was excluded by relevant tests including immunoglobulin,autoantibody,color ultrasound,and clinical evaluation.We collected detailed baseline data such as age,gender,24 hours urinary protein,serum creatinine,albumin quantitative,immunoglobulin,anti-PLA2R antibodies,serum total cholesterol,kidney pathology,etc.Patients,anti-PLA2R antibody levels were detected by indirect immunofluorescence.According to the serum anti-PLA2R antibody levels,the patients were divided into two groups: negative group and positive group,and the positive group was divided into two subgroups: high antibody level group(≥1:200)and low antibody level group(≤ 1:100).The correlations between baseline anti-PLA2R antibody and baseline clinical parameters were investigated in IMN patients;The 44 IMN patients with positive anti-PLA2R antibodies were treated with corticosteroid combined with cyclosporine as the initial therapy,among them the high antibody level group(20 cases)and the low antibody level group(24 cases).The results of urine protein,serum creatinine and anti-PLA2R antibody were collected before treatment,1 month,3 months and 6 months after treatment,and analyze the correlation between antibody titers and the treatment effect of immunosuppressive agents in the treatment of IMN;The Patients treated with conservative supportive therapy without corticosteroid and immunosuppressive agents were collected and the correlation between anti-PLA2R antibody and spontaneous remission of IMN was investigated.Results: A total of 68 patients with IMN were collected,including 49 males(72.1%),There were 57 cases with positive antibody and 11 cases with negative antibody.Compared with the antibody-negative group,the antibody-positive group were older((58.9±9.3)years VS(44.2±14.1)years,P<0.05),The antibody-positive group had higher levels of urinary protein((5.2±1.7)g VS(3.4±0.9)g,P<0.05),lower levels of serum albumin((20.1±4.0)g/L VS(24.0±3.7)g/L,P<0.05),higher cholesterolemia,and higher incidence of nephrotic syndrome.There were no significant differences in the levels of uric acid,creatinine,complement C3,C4,immunoglobulin Ig A,Ig M and Ig G between the two groups.Stage II membranous nephropathy was the main pathological stage in both groups.Compared with the antibody negative group,the positive rate of glomerular Ig G4 deposition was higher in the antibody positive group,while the positive rates of glomerular Ig G1,Ig G2,Ig G3,Ig A,Ig M,C1 q and C3 showed no significant difference between the two groups;Fifty-seven anti-PLA2R antibody positive patients were divided into two subgroups: high antibody level group(≥1:200)and low antibody level group(≤1:100).Compared with the low antibody level group,the high antibody level group had higher mean 24-hour urinary protein and lower mean albumin,but there was no statistical difference.There was no significant difference in sex composition ratio,age,cholesterol and serum creatinine between the two groups;A total of 44 cases of anti-PLA2R antibody positive IMN patients treated with cyclosporine combined with corticosteroid were collected,24 cases in the low antibody level group and 20 cases in the high antibody level group.The total remission rate in the low antibody level group was higher than that in the high antibody level group at 3 and 6 months after treatment(P<0.05).After 3 months of treatment,The Percentage from antibody positive to antibody negative was higher in the low antibody level group than that in the high antibody level group(P<0.05).and there was no statistical difference After 6 months of treatment between the two groups.After 6 months of maintenance treatment,these 44 patients were divided into remission group and non-remission group according to the treatment results.Baseline anti-PLA2R antibody levels were significantly lower in the remission group than that in the non-remission group,and Baseline urinary protein levels were not statistically different between the two groups.The Percentage from antibody positive to antibody negative in the remission group at 1,3 and 6months after treatment was higher than that in the non-remission group at the same period.The 15 IMN patients received conservative supportive treatment were followed up for 6 months.The spontaneous remission rate was higher in the anti-PLA2R antibody negative group62.5%(5/8)compared with the anti-PLA2R positive group 28.5%(2/7),but the difference was no statistically significant.According to the treatment effect,all the patients were divided into remission group and non-remission group.The antibody negative rate before treatment in the remission group was 71.4%(5/7),which was higher than that in the non-remission group(37.5%,3/8),but the difference was not statistically significant.After 6 months,the antibody negative rate in the remission group was 100%,which was higher than that in the non-remission group(37.5%),and the difference was statistically significant.Conclusion1.In adult IMN patients,baseline anti-PLA2R antibody was correlated with urinary protein,serum albumin and cholesterol.Compared with antibody-negative IMN patients,serum antibody-positive patients showed more urinary protein,more severe hypoalbuminemia,and higher cholesterolemia.In antibody-positive IMN patients,more detail of correlation between the baseline antibody level and the condition of IMN patients needs to be further confirmed by large sample.2.Patients with anti-PLA2R antibody positive IMN treated with corticosteroid combined with cyclosporine had higher remission rate and better short-term prognosis in low antibody level group compared with high antibody level group.3.Baseline anti-PLA2R antibody has great potential to predict spontaneous remission in adult IMN.4.The dynamic changes of antibodies are related to IMN disease activity,which has important guiding value for disease assessment,prognosis and treatment.