Significance Of PLA2R And Its Antibodies In Diagnosis And Treatment Of Idiopathic Membranous Nephropathy

Objective:In this study,the expression of M-type Phospholipase A2 Receptor(M-PLA2R)in renal tissues and the level of antibody in serum were detected to investigate the diagnostic value and its correlation with prognosis and therapeutic effect in patients with Idiopathic Membranous Nephropathy(IMN).Methods:A single-center retrospective analysis was performed on 68 patients with Idiopathic Membranous Nephropathy(IMN)and 20 non-IMN patients who were diagnosed by renal puncture biopsy from Affiliated Hospital of Chengde Medical College from January 2016 to December 2018.68 Patients with Idiopathic Membranous Nephropathy(IMN)is experimental group and 20 non-IMN patients is the control group.Immunohistochemistry(IHC)staining was used to detect the expression of Phospholipase A2 Receptor(PLA2R)in renal tissue.Enzyme linked Immunosorbent Assay(ELISA)was used to detect serum anti-PLA2R antibody level.The correlation between serum PLA2R antibody and the expression of PLA2R in renal tissue was analyzed,and the clinical data of serum creatinine,urea nitrogen,blood lipid,albumin,24 h urine protein and other clinical data of IMN patients before and 6 months After treatment with glucocorticoids combined with cytotoxic drugs or calmodulin inhibitors were collected to analyze the correlation of PLA2R in renal tissue and its antibody for the clinical characteristics,treatment effect and prognosis of Idiopathic Membranous Nephropathy.Results: 1 Expression of PLA2R and its antibodies:There are 52 patients with PLA2R positive in renal tissue in the experimental group,including 17 cases with strong positive,33 cases with medium positive,2 cases with weak positive and 16 cases with negative.The percentage of positive patients was 76.5%.In the control group,there were 20 patients,including 3 PLA2R positive patients,including 0 strong positive patients,2 moderate positive patients and 1 weak positive patient,with a positive rate of 15.0%.There were 49 patients in IMN group with serum anti-PLA2R positive,accounting for 72.1% of the total.Among the 19 patients with complete data in the non-IMN group,1 was positive for PLA2R antibody,with a positive rate of 5.3%.The difference of kidney tissue PLA2R and its antibody between the two groups was statistically significant(P<0.05).2 Relationship between kidney tissue PLA2R and serum anti-PLA2R antibody:40 cases of kidney tissue PLA2R and serum anti-PLA2R antibody were both positive in IMN,accounting for 76.9% of the patients with positive PLA2R expression.Among the 19 patients with negative antibody,12 showed positive expression of PLA2R in renal tissue,and 7 showed negative expression of renal tissue antigen and serum antibody.In the non-IMN group,0 case of renal tissue PLA2R and serum anti-PLA2R antibodies was positive at the same time,3 cases of serum anti-PLA2R antibodies were negative but renal tissue PLA2R was positive,and 15 patients were both negative for renal tissue antigens and serum antibodies.3 Diagnostic value of kidney tissue PLA2R and its antibodies:The diagnostic sensitivity of kidney tissue PLA2R alone is 76.47%,the specificity is 84.21%,and the positive likelihood ratio is 4.84.The sensitivity of serum anti-PLA2R antibody alone for diagnosis was 72.06%,the specificity was 94.74%,and the positive likelihood ratio was 13.70.If one positive for kidney PLA2R or serum anti-PLA2R antibody is considered to diagnose IMN,the combined detection of kidney PLA2R and its antibodies has a sensitivity of 89.71%,specificity of 78.95%,and a positive likelihood ratio of 4.26.4 Analysis of general clinical data for different expressions of PLA2R in IMN patients:There were differences in creatinine between PLA2R positive and negative patients in renal tissue(P=0.003),The creatinine level in the PLA2R positive group was significantly lower than that in the PLA2R negative group,and no statistically significant differences in gender,age,systolic blood pressure,diastolic blood pressure,albumin,and 24 h urine protein(P>0.05).5 Comparison of general clinical data of PLA2R-Ab positive and negative patients in IMN group:There were no statistically significant differences in gender,age,systolic blood pressure,diastolic blood pressure,creatinine and urea nitrogen between the two groups(P>0.05).Serum albumin in the positive group was 26.15±4.70g/L,while serum albumin in the negative group was 32.29±7.22g/L.The difference between the two groups was statistically significant.The albumin level in the antibody positive group was lower than that in the antibody negative group(P=0.003).The 24-hour urine protein level of the positive group was 7.24(4.56,12.99)g/24 h,and that of the negative group was 4.90(1.55,8.21)g/24 h.The difference between the two groups was statistically significant.The 24-hour urine protein level of the antibody positive group was higher than that of the antibody negative group(P=0.012).6 Remission of kidney tissue PLA2R with different expressions in IMN patients:After 6 months of treatment with glucocorticoids combined with cytotoxic drugs or calmodulin inhibitors,the remission rate of PLA2R positive patients was 36.4% and the remission rate of PLA2R negative patients was 75%.Fisher’s exact probability method used to compare the remission of the two groups of patients after 6 months of treatment with glucocorticoids combined with cytotoxic drugs or calmodulin inhibitors,the difference was not statistically significant(P=0.101).7 Remission of patients with different expression of serum PLA2R-Ab in IMN group:After 6 months of treatment with glucocorticoids combined with cytotoxic drugs or calmodulin inhibitors,the remission rate was 28.6% in the PLA2R-Ab positive group and 83.3% in the PLA2R-Ab negative group,with a significant difference in remission between the two groups(P=0.027).It can be considered that the remission rate of the PLA2R-Ab positive group is significantly lower than that of the PLA2R-Ab negative group.8 Antibody titer analysis of the remission group and the invalid group in the IMN group:The general clinical data of the two groups showed no significant difference in age,blood pressure,creatinine,urea nitrogen,albumin,and 24 h urine protein(P>0.05).The titer of PLA2R-Ab in the remission group was 46.59±37.53RU/ml,while the titer of PLA2R-Ab in the invalid group was 80.58±56.17RU/ml.There was a significant difference in the titer of PLA2R-Ab between the two groups,and the titer of antibody in the invalid group was higher than that in the remission group(P=0.022).Conclusions: 1 The positive rates of renal tissue PLA2R and serum anti-PLA2R antibody in IMN patients were significantly higher than those in the control group,and the two had specificity as diagnostic indicators of IMN.2 The expression of PLA2R in renal tissue was not associated with disease activity 3 Serum anti-PLA2R antibody titer level is closely related to disease activity.Patients with a high antibody titer respond less well to treatment and the disease is more mobile,while patients with a low antibody titer respond better to treatment and have better prognosis.