Towards optimizing use of PLA2R antibody testing in membranous nephropathy

Excerpt

The ability to detect and measure autoantibodies to the target antigen M-type phospholipase A2 receptor (PLA2R) in patients with membranous nephropathy (MN) has been revolutionary for understanding and diagnosing MN, as well as monitoring humoral disease activity by following the trend of PLA2R-Ab titers. The definition of PLA2R-Ab seropositivity can vary depending on the specific assay used and its reference range. There are two FDA-approved commercial assays available for PLA2R-Ab: a cell-based indirect immunofluorescence test (IIFT) and an enzyme-linked immunosorbent assay (ELISA), both of which detect total IgG against PLA2R [1]. According to manufacturer instructions for the IIFT, a positive signal at 1:10 defines seropositivity. For the ELISA, a clear positive assay is represented by a titer > 20 RU/mL, while a titer in the 14–20 RU/mL range is considered borderline, and < 14 RU/mL is considered negative. These thresholds were established based on the study by Dahnrich et al. that included 200 cases of primary MN, 230 other kidney diseases, 316 other autoimmune diseases, and 291 healthy individuals [1]. While many clinical laboratories and most publications in the field use these definitions for seropositivity, several studies have shown that using a much lower ELISA cutoff (2–3 RU/mL) increases sensitivity without sacrificing specificity, and therefore more accurately defines seropositivity [2‐5]. …