Diagnostic and prognostic value of Anti-phospholipase A2 receptor antibodies in patients with membranous nephropathy

ABSTRACT Objective: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Although kidney biopsy is the gold standard method in the diagnosis of MN, it is an invasive procedure that involve risks such as pain and bleeding. In recent years, phosholipase A2 receptor antibody (anti-PLA2R) has been identified as a promising diagnostic biomarker. This study aimed to investigate the diagnostic and prognostic value of anti-PLA2R antibody in patients with MN by using two different commercial Enzyme-Linked ImmunoSorbent Assay (ELISA) kits, and to determine the most optimal cut-off values. Materials and Methods: This study included 74 patients who were followed up with a diagnosis of primary membranous nephropathy (PMN), secondary membranous nephropathy (SMN) or non-MN nephrotic syndrome at Karadeniz Technical University Faculty of Medicine, Department of Nephrology, between June 2022-June 2023. 15 healthy individuals were also included. Anti-PLA2R antibody levels were assessed with two different commercial ELISA kits (Euroimmun, Lübeck, Germany and MyBioSource, San Diego, California, USA). Clinical biochemistry test results were obtained from hospital records. Results: When the Euroimmun ELISA kit was used at a cut-off of 20 RU/ml in accordance with the manufacturer's recommendations, sensitivity was detected 30% and specificity was 100%. When receiver operating characteristic (ROC) analysis was performed, the cut-off value of the Euroimmun ELISA kit for our study was found to be 1.19 RU/ml. When this cut-off value was used, the sensitivity of the test was found to be 66.6% and the specificity was 72.7%. When the cut-off value of 2 RU/ml was used, sensitivity was increased to 46.6% and specificity remained 100%. Such a cut-off value could not be determined with the ROC curve analysis of the concentration values determined by the MyBioSource ELISA kit. In the Euroimmun ELISA kit, antibody-positive patients were found to have higher mean proteinuria (p=0.015) and lower mean albumin (p=0.010) levels than negative patients. Average hemoglobin (p=0.030) and hematocrit (p=0.039) values were found to be lower in anti-PLA2R antibody positive patients who have PMN compared to negative patients. Conclusion: In this study, it has been determined that when the cut-off value recommended by the manufacturer is used in the Euroimmun ELISA kit, a positive result is more useful and eliminates the need for biopsy, while a negative result should be confirmed by biopsy. Further studies are needed to determine the optimal cut-off value for both test kits. Antibody positivity was found to be associated with high proteinuria levels and low hemoglobin/hematocrit values; it may be associated with the progression of MN to chronic renal failure and may indicate that this antibody can be used as a prognostic biomarker.