Abstract
BackgroundAutoantibodies against-phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (iMN). Enzyme-linked immunosorbent assay (ELISA) is becoming the preferred method in many laboratories for the determination of anti-PLA2R antibodies, because it provides quantitative results, and is not prone to subjective interpretation, as is the case with indirect immunofluorescence assay.MethodsThe purpose of our study was to determine the diagnostic performance of serum PLA2R antibodies detected by commercially available ELISA in a large Italian multicenter cohort of patients with biopsy-proven iMN and in patients with other renal diseases, with special focus on evaluating the optimal cut-off value to discriminate positive and negative results. A total of 495 consecutive patients were recruited. Renal biopsies were performed in all patients, and blood samples were taken before the initiation of immunosuppressive treatment.ResultsAccording to the clinical diagnosis and to kidney biopsy, 126 patients were diagnosed with iMN and 369 had other non-membranous nephropathies. Anti-PLA2R autoantibodies were detected using a commercial anti-PLA2R ELISA. At a cut-off value of 20 relative units (RU)/ml indicated by the manufacturer for positive classification, sensitivity was 61.1% and specificity 99.7%. At a cut-off value of 14 RU/ml indicated by the manufacturer for borderline results, sensitivity was 63.5% and specificity remained the same (99.7%). At a cut-off of 2.7 RU/ml, selected as the optimal cut-off on the basis of ROC curve analysis, sensitivity was 83.3% and specificity 95.1%. The best overall efficiency of the test was observed at 2.7 RU/ml; however, the highest positive likelihood ratio and diagnostic odds ratio were achieved at 14 RU/ml. A cut-off threshold higher than 14 RU/ml or lower than 2.7 RU/ml entailed worse test performance.ConclusionDepending on the clinical use (early diagnosis or as a support to confirm clinical diagnosis), nephrologists may take advantage of this evidence by choosing the most convenient cut-off. However, renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity.
Highlights
Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults
We evaluated anti-phospholipase A2 receptor (PLA2R) antibody Enzyme-linked immunosorbent assay (ELISA) results at the two different cut-offs suggested by the manufacturer for negative and positive classification (14 and 20 relative units (RU)/ml, respectively), and at cut-off values obtained by receiver operating characteristic (ROC) curves
The presence of serum anti-PLA2R autoantibodies has an important impact on the diagnosis of idiopathic membranous nephropathy (iMN), helping in differentiating it from sMN and other nephropathies [11]
Summary
Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. MN can be either idiopathic (iMN) or secondary (sMN) to various clinical conditions, including systemic autoimmune diseases, infections, neoplasia and drug intoxication [1,2,3]. Mass spectrometry of the reactive protein band detected the phospholipase A2 receptor (PLA2R), a membrane glycoprotein located on the normal renal glomerular podocytes and present in kidney immune deposits, indicating that PLA2R is a major antigen in this disease. This finding led to the subsequent development of anti-PLA2R antibody tests as an aid in the differential diagnosis of iMN from sMN and other nephropathies displaying similar clinical features [4,5,6]. Renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
