Abstract
Background:Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans.MethodsThis was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated.ResultsOf the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32).ConclusionGlomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.
Highlights
Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN)
Demographic and Clinical Characteristics Overall, there were eighty-eight (88) patients included in this study: 41 with PMN, 19 with pure class V lupus nephritis (LN-V) and 28 with diabetic nephropathy (DN)
We found a respective frequency of occurrence of positive glomerular staining for PLA2R and THSD7A in 51.2% (21/41 patients) and 4.9% (2/41 patients) of biopsies initially categorized as PMN
Summary
Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. While quantitative and semi-quantitative serologic assays are commercially available for PLA2R and THSD7A antibodies, it has been noted that a significant number of individuals with histologically confirmed antigens to PLA2R in glomerular deposits (and a biopsy diagnosis of PMN) have negative PLA2R serology results.[10] It has been shown that early in the time course of PMN, due to delayed seroconversion, PLA2R may be negative in serum but demonstrable in histologic specimen.[11] Kidney biopsy tissue-based testing may be a veritable diagnostic tool in appropriately identifying PMN
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