Autoimmune Diagnostics

Nephrology

Disease – Primary Membranous Glomerulonephritis: Primary membranous glomerulonephritis (pMGN) is a chronic inflammatory disease of the glomeruli which is accompanied by a progressive impairment of the kidney function. The autoimmune mechanism of primary MGN, which was first discovered and described in 2009, is the result of autoantibodies reacting with phospholipase A2 receptors (PLA2R, transmembrane glycoproteins), which are expressed in human glomeruli on the surface of podocytes. They are involved in regulatory processes in the cell following phospholipase binding. Up until now, two main groups of PLA2R have been des ribed (types M and N), with the M type identified as the major target antigen of the autoantibodies. The antigen/antibody complexes (immune deposits) are formed in situ in the glomerular basement membrane of patients with primary MGN. They trigger complement activation with overproduction of collagen IV and laminin. Alternatively, the autoantibodies can function as agonists or antagonists of the receptors. This causes damage to the podocytes due to destruction of the cytoskeleton and broadening of the basement membrane, leading to protein entering the primary urine, and subsequently proteinuria.

Primary_Membranous_Nephropathy
Immunhistochemical photos from Hoxha E, Kneißler U, Stege G, et al. Antiphospholipase A2 Receptor Antibody Titer and Subclass in Idiopathic Membranous Nephropathy. Kidney Int. 82(7): 797-804 (2012)

Diagnostics:The identification and characterization of PLA2R (type M) as the target antigen of circulating antibodies in primary MGN has proven to be of major importance for non-invasive diagnostics. Autoantibodies of class IgG against PLA2R are highly specific for primary membranous glomerulonephritis and can be found in the serum of up to 80% of patients with primary MGN. In contrast, they are not exhibited by healthy blood donors or patients with secondary MGN.

EUROIMMUN recombinant-cell IFT (RC-IFT) and ELISA are available for the determination of autoantibodies against PLA2R. The anti-PLA2R RC-IFT uses transfected cells as standard substrate, while the anti-PLA2R ELISA is based on human recombinant receptors purified from transfected cells. RC-IFT and ELISA are suitable for qualitative and quantitative detection of human autoantibodies of class IgG against PLA2R.

The anti-PLA2R IFT and ELISA are FDA cleared. Testing is available at Cincinnati Children’s Hospital Medical Center, Massachusetts General Hospital, and Nephropath.