Analysis Of Prognostic Value And Clinical Responses Of Serum Anti-PLA2R Antibodies In Patients With Idiopathic Membranous Nephropathy

Beckgroud : The predictive value and clinical responses to treatment of anti-M-type phospholipase A2 receptor(PLA2R) autoantibodies for idiopathic membranous nephropathy(IMN) remains controversial.Objective: To investigate the role of serum PLA2 R antibody in the prognosis of idiopathic membranous nephropathy patients, and to evaluate response to treatment.Methods:(1) We evaluated the prognostic value of serum PLA2 R antibodies regarding clinical outcome and assessed the clinical responses to treatment of the dynamics of PLA2 R antibody titers in a well-difined cohort of 46 idiopathic membranous nephropathy patien with follow-up; patients were subdivided into with or without detectable anti-PLA2 R antibodies at baseline on IIFT testing.(2) Since corrected serum aPLA2 R levels for treatment factors, we measured autoantibodies in serum samples obtained at the time of biopsy from a total of 8 patients with IMN who diagnosed IMN by renal biopsy and were treated with tacrolimus for at least 12 months, The change of the serum PLA2 R antibodies before and after treatment for 12 months was observed.(3) PubMed, Web of sciences, OVID and CNKI, WanFang Data, CBM was searched for collecting cohort studies on the correlation between PLA2 R antibodies expression and prognosis of membranous nephropathy, and relevant articles were also retrieved from inception to Jan 2016. Two reviewers independently screened the literature, extracted the data, and evaluated the quality. Then the meta-analysis was performed by using RevMan5.0 software.Result:(1) We observed that autoantibody reactivity reflected the severity of disease activity.Proteinuria were more severe in patients with anti-PLA2 R than in those without the autoantibodies(6.06±4.87 g/24 h vs 2.28±1.98 g/24 h, P<0.001). The clinical severities worsened proportionally and Protein urine,hypoalbuminemia as the levels of anti-PLA2 R antibodies increased(P<0.005, respectively). Receiver Operating Characteristic(ROC) analysis resulted in an area under the curve(AUC) of 0.79(95% CI 0.635-0.945, P<0.05). 98.7% specificity and58.3% sensitivity. Base on the result of AUC, patients were subdivided into low or high antibody levels according to the serum PLA2 R antibody titer 1:32, Form the curve of K-M,we found that the rate of remissions occurred significantly less frequently among patients with high antibody titers(66.7% vs 83.3%,P<0.05 in the lowest and highest tertiles, respectively).(2) In 8 patients who treated with tacrolimus, 1 case of serum antibody negative patients achieved complete remission, 3 cases of serum PLA2 R antibody positive patients achieved complete remission, 2 cases of positive patients achieved partial remission, 2 cases of positive patients were no remission. Furthermore, we observed that no remissions occurred in patients with high anti-PLA2 R levels(1:100). The decline in anti-PLA2 R precedes the corresponding changes in proteinuria. 3 cases sustained negative serum PLA2 R antibody within the 5 cases who achieved complete remission. One cases with negative anti-PLA2 R were seropositive at the time of recurrence.(2) Finally 8 cohort studies involving 562 patients were included. The meta-analysis showed that, patients with PLA2 R antibodies positive had poor overall remission[OR=0.82, 95%CI(0.73, 0.92), P<0.0006]. Furthermore, patients with high level of PLA2 R antibodies had poor overall remission [OR=0.71, 95%CI(0.52, 0.96), P<0.05]. On the other hand, those patients with high level of anti-PLA2 R in terms of poor clinical outcome.Conclusions: Circulating anti-PLA2 R autoantibodies may help in monitoring disease activity, predict outcome and guiding personalized immunosuppressive treatment strategy in nephrotic patients with idiopathic membranous nephropathy.