The Role of Anti-PLA2R and Anti-THSD7A Antibodies in the Pathogenesis and Diagnostics of Primary Membranous Nephropathy: A Review of Current Knowledge for Clinical Practice

Abstract

Primary membranous nephropathy (PMN) is considered a major cause of nephrotic syndrome. The discovery of circulating autoantibodies directed against glomerular podocytes helped to classify them as autoimmune diseases. Over the past years, there has been an increasing significance of anti-Phospholipase A2 Receptor (anti-PLA2R), which has been detected in 70–80% of PMN cases, and relevance of anti-Thrombospondin type I domain-containing 7A (anti-THSD7A) even though they are present in 2–5% of patients. The results of clinical and experimental studies indicate that these antibodies are pathogenic. It radically changed the diagnostic and therapeutic approach. Measurement of antibody titers in the serum seems to be a valuable tool for identifying PMN and for the assessment of disease activity. By monitoring pathogenic antibodies levels rather than proteinuria or reduced glomerular filtration rate (GFR) as an indicator of glomerular disease, physicians would easier divide patients into those with active and inactive PMN disease and decide about their therapy. The aim of this review is to evaluate scientific evidence about the role of autoantibodies, namely anti-PLA2R and anti-THSD7A, as PMN biomarkers. The present manuscript focuses on PMN pathogenesis and key data of diagnosis, monitoring of the disease, and treatment strategies that are currently being used in clinical practice.

Primary Membranous Nephropathy - what do we know today?

“…M-type phospholipase A2 receptor (PLA2R) is a transmembrane glycoprotein belonging to the mannose receptor family, which is expressed on podocytes. Antibodies against PLA2R can be found in kidney biopsy specimens as well as circulating in the blood [12]. The presence of anti-PLA2R-Ab in diagnostic levels has been revealed in 50-80% of patients, as studies show [13].…”

A review of progress on complement and primary membranous nephropathy

“…The antibodies against these circulating or subepithelial antigens are predominantly of the IgG4 subclass. [11][12][13][14][15][16] However, IgG4 cannot bind to C1q. [17] Complements are essentially a series of proteins that, upon activation, exhibit enzymatic activity and are widely distributed in fresh serum, cell membrane surfaces, and tissue fluids of humans and animals.…”

“…The antibodies against these circulating or subepithelial antigens are predominantly of the IgG4 subclass. [11–16] However, IgG4 cannot bind to C1q. [17]…”