IMN is the main cause of nephrotic syndrome in adults. Although this condition may spontaneously go into remission, a significant number of patients (up to 40%) progress to end stage renal disease. Renal biopsy is the gold standard for diagnosing membranous nephropathy, because specific serological markers were not available so far. Lots more, outcome predictors as well as prognostic biomarkers, helping to identify response to immunosuppressive treatment, would be of utmost usefulness. Recently, an important role for autoantibodies recognizing podocytes antigens has been suggested. Different podocyte proteins have been reported as the target of the immune response in IMN. However, circulating antibodies directed towards the M-type phospholipase A2 receptor (PLA2r) seem to play a major role in the development of the disease, being present in 52-78% of cases (Figure 1) (Figure 2).
AIMS OF THE STUDY
To assess the prevalence of anti-PLA2r antibodies in a large cohort of IMN patients •to correlate their presence and titer with disease activity and clinical parameters.
PATIENTS & METHODS
Patients: 100 newly diagnosed IMN, 30 non-membranous primary GN, 48 secondary GN, and 43 healthy controls. 9 IMN anti-PLA2r +ve pts were followed-up. AutoAbs levels were evaluated at diagnosis/biopsy and 1 & 3 months after starting immunosuppression, or during the “conservative” treatment.
Method: Indirect Immunofluorescence Technique using HEK293 cells transfected with the specific c-DNA as substrate (anti-PLA2r IIFT, Euroimmun).
Anti-PLA2r, measured by IIF assay, were present in 69/100 IMN patients but only in 2/78 glomerular disease controls; all healthy controls were negative (Figures 3, 4). In this selected “high-prevalence” clinical setting the PPV of a +ve test result for diagnosis of IMN was 97.6%. Anti-PLA2r did not correlate with basal uProt, sCreat, sProt and sAlb. Anti-PLA2r levels decreased during the short-time follow-up in 7 out of 8 treated patients (Ponticelli regimen or Rtx) that went into partial or complete clinical remission, while increased in pt n° 9, who did not respond to the therapy (Figure 5).
Anti-PLA2r antibodies are present in about two-thirds of IMN sera, but only occasionally found in non-membranous primary GN or secondary GN. Such high prevalence and specificity suggest a pathogenetic role of such autoantibodies, and strongly support the diagnostic usefulness of the novel anti-PLA2r assay. Correlation between anti-PLA2r levels and clinical parameters is ongoing. However, to evaluate the prognostic potential of such biomarker a great collaborative effort is needed, to set up large and prospective studies, enrolling patients with detailed clinical data.