Primary Membranous Nephropathy Autoantibody Profile*

Overview:

Use: This autoantibody profile is recommended for the evaluation of patients at risk for primary membranous nephropathy (PMN).

PMN represents a kidney-specific autoimmune disorder initiated by the presence of circulating antibodies directed against specific native podocyte antigens, particularly PLA2R (phospholipase A2 receptor) and THSD7A (human thrombospondin, type I, domain containing 7A). PMN is characterized by the accumulation of immune complexes at the glomerular filtration barrier, leading to detrimental glomerular damage. It is noteworthy that PMN stands as the most prevalent cause of idiopathic nephrotic syndrome in non-diabetic adults. The disease's progression varies considerably, with some untreated patients experiencing spontaneous remission, while others face a deterioration that ultimately leads to end-stage renal disease (ESRD). In the diagnosis and ongoing monitoring of PMN, conventional kidney function tests and kidney biopsies remain in use. Nonetheless, the role of serum testing for PLA2R and THSD7A antibodies in PMN diagnosis, prognosis and disease tracking is becoming increasingly significant.

Approximately 70% of individuals with PMN can be identified as having circulated PLA2R antibodies, and these antibodies exhibit an almost 100% specificity for PMN. Given the high specificity of these antibodies, it may not be necessary to perform a kidney biopsy when PLA2R antibodies are found in patients at low risk of disease progression or at high risk of complications associated with the biopsy. Additionally, the concentration of PLA2R antibodies carries prognostic significance. Lower antibody levels are linked to a higher chance of experiencing spontaneous remission, while higher concentrations are associated with the development of nephrotic syndrome (if not initially present) and a decline in kidney function. Patients with undetectable antibody levels following treatment are more likely to remain in remission for at least five years, while those with less than a 50% reduction in antibodies at the end of treatment are to have treatment-resistant disease. Circulating THSD7A antibodies are found in 3% to 9% of PMN patients, and they exhibit a high specificity, potentially up to 100%, for PMN, as they have not been detected in healthy individuals or those with other renal or systemic diseases. THSD7A antibodies have been reported to decrease before achieving remission and increase before experiencing a relapse. Recurrence of PMN is a common occurrence after kidney transplantation, with the highest incidence within the first-year post-transplant and again after four to five years. For individuals with PLA2R-related PMN who have undergone kidney transplantation, vigilant monitoring of antibody concentrations can aid in predicting relapse. In patients with THSD7A-related PMN, elevated antibody levels at the time of transplant are associated with the recurrence of the disease.

If PLA2R Antibody, IgG is positive, then a PLA2R Antibody, IgG titer will be added. If THSD7A Antibody, IgG is positive, then a THSD7A Antibody, IgG titer will be added.

Limitations: This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Methodology: Transfected cell-based semi-quantitative indirect immunofluorescence assay (IFA)

*If this test reflexes additional charges will apply