The Significance Of PLA2R And Its Antibody In The Diagnosis And Treatment Of Membranous Nephropathy

Objective:To detect M-type phospholipase A2 receptor(M-PLA2R) in renal tissue of patients with idiopathic membranous nephropathy(IMN) and secondary membranous nephropathy(SMN) and the serum anti-PLA2 R antibody positive rate in those patients, as well as to evaluate the value of PLA2 R in renal tissue and serum anti-PLA2 R antibody in the diagnosis of membraneous nephropathy; to explore the relationship between PLA2 R of renal tissue or serum anti-PLA2 R antibody and clinical features of MN.Methods : Collected renal tissue samples diagnosised of IMN, hepatitis B virus associated membranous nephropathy(HBV-MN), type V lupus nephritis(LN-V), minimal change disease(MCD) by renal biopsy and normal renal tissue samples from January 2011 to December 2014 in the People’s Hospital of Sichuan Province, we used immunehistochemistry(IHC) staining to detecte PLA2 R antigen in renal tissue; At the same time we collected serum samples which completed renal biopsy within 3 days and used enzyme linked immunosorbent assay(ELISA) to detect serum anti-PLA2 R antibody concentration. We calculated the positive rate in different diseases and sensitivity, specificity and coincidence rate of PLA2 R and anti-PLA2 R antibody alone or in combination when used in the differential diagnosis of IMN and SMN. We used SPSS21.0 software to make the receiver operator characteristic curve(ROC); Collected the clinical and follow-up data of IMN patients to analyze the relationship between PLA2 R in renal tissue, serum anti-PLA2 R antibody and clinical characteristics and treatment value of membranous nephropathy.Results:1. The expression of PLA2 R in renal tissue: the positive rate of PLA2 R expression in renal tissue in IMN, HBV-MN, LN-V, MCD and normal control group was 50/61(81.9%), 5/8(62.5%), 5/14(35.7%), 5/13(38.4%) and 0/5(0).2. The expression of anti-PLA2 R antibody: If serum anti-PLA2 R antibody concentration is more than or equal to 20 RU/ml regarded as positive diagnosis threshold, the positive rate of the IMN group and HBV-MN group were 103/160(64.38%) and 3 / 8(37.5%); there was no positive expression in LN-V, MCD groups and the normal control group.3. PLA2 R in renal tissue and serum anti-PLA2 R antibody diagnostic value: the sensitivity of single PLA2 R in renal tissue in the differential diagnosis was 92.68%, the specificity was 54.55%; the sensitivity of single serum anti-PLA2 R antibody was 75.61%, the specificity was 86.36%; if anyone of PLA2 R in renal tissue and serum anti-PLA2 R antibody is positive can be diagnosed as IMN, then the sensitivity was 95.12%, the specificity was 54.55%. Used SPSS21.0 software to produce ROC curve, the area under the PLA2 R in renal tissue and the serum anti-PLA2 R antibody curve was 0.736(95%CI:0.594-0.878) and 0.810(95%CI:0.695-0.924) respectively.4. Treatment response in patients with IMN: Serum Anti-PLA2 R antibody concentration from high to low is: P+CTX group, P+CNI group, conservative or single hormone treatment group, compared with the conservative or single hormone treatment group and P+CTX group, the difference has statistical significance(P=0.013); Kaplan- Meier survival curve analysis showed that compared with conservative or single hormone treatment group and P+CNI treatment group, remission time is longer and remission rate is lower in P+CTX treatment group, the difference is statistically significant(P < 0.05); there were more high-risk patients in P+CTX group and P+CNI group(c2=10.728,P=0.001), more low risk patients in conservative or single hormone treatment group(c2=17.066, P=3.6*10-6), the difference is statistically significant.5. PLA2 R in IMN patients and response to treatment: Kaplan-Meier survival curve analysis showed cumulative remission rate of positive and negative group of PLA2 R in renal tissue had no significant difference(P=0.278); but serum anti-PLA2 R antibody negative group than that in the positive group of patients obtained faster response and higher remission rate, the difference has statistical significance(P=0.030), risk stratification analysis displayed difference was not statistically significant(c2=0.762, P= 0.383).6.Comparative analysis in remission group and ineffective group of IMN patients: serum albumin in remission group is higher than in ineffective group, and the difference is statistically significant(P=0.016); concentration of serum anti-PLA2 R antibody in ineffective group was higher than that in the remission group, the difference has statistical significance(P=0.018); risk stratification comparation showed the difference had no statistical significance(c2=2.765, P=0.096).7. Multivariate Cox regression analysis showed that serum anti PLA2 R antibody was associated with poor prognosis in IMN patients(RR=2.615, 95%CI:1.244-5.499, P=0.011).Conclusions:1. The expression of PLA2 R and its antibody in IMN patients was significantly higher than that in HBV-MN, LN-V, MCD and normal control group. The serum anti PLA2 R antibody was the specific antibody of IMN.2. The serum anti PLA2 R antibody was better than PLA2 R in renal tissue in the diagnosis of membranous nephropathy.3.Serum anti-PLA2 R antibody concentration influence curative effect:the negative and low titer patients obtained faster response and the remission rates are higher than the positive and high titer patients; Serum anti PLA2 R antibody positive is independent related to the poor prognosis of patients. 4.The effect of treatment with P+CNI is better than that of P+CTX group, the former was relieved faster and the response rate was higher.