In membranous nephropathy (MN), which is characterized by deposition of immune complexes along the glomerular basement membrane (GBM), phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A are target antigens in approximately 70% and 1%-5% of cases of primary MN, respectively.
We conclude that the novel anti-THSD7A ELISA can be used to identify patients with THSD7A-associated MN and to monitor autoantibody titers during treatment.
Taken together, these 2 cases suggest that immunoadsorption could be a useful tool in the treatment of patients with THSD7A antibody-positive membranous nephropathy.
While there is an increasing understanding of primary MN with the discovery of antibodies directed against phospholipase A2 receptor (PLA2R Ab) and thrombospondin type 1 domain-containing 7A, circulatory factors causative of inducing MCD and FSGS remain in part elusive.
It has been reported that phospholipase A2 receptor (PLA2R) is the first autoantigen involved in idiopathic membranous nephropathy and thrombospondin type-1 domain-containing 7A (THSD7A) may have a close relationship with malignancy-related membranous nephropathy.
While the pathogenesis of MN is still controversial, the detection of autoantibodies against two specific glomerular antigens, phospholipase A2 receptor (PLA<sub>2</sub>R) and thrombospondin type 1 domain containing 7A (THSD7A), together with the beneficial effect of therapies targeting B cells, have highlighted the main role of autoreactive B cells driving this renal disease.
Circulating antibodies against M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A in Chinese patients with membranous nephropathy.
Autoantibodies both to the M-type phospholipase A2 receptor (PLA2R) and to thrombospondin type-1 domain-containing 7A (THSD7A), initially described in adult MN, have now been identified in children and adolescents with MN and serve as a useful diagnostic and monitoring tool in this younger population as well.
The identification of antibodies directed against the M-type phospholipase A<sub>2</sub> receptor (PLA2R) and thrombospondin type-1 domain-containing 7A protein have added a new perspective on diagnosis, monitoring the immunological activity, predicting prognosis and guiding therapy in patients with primary MN.
The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism.
Notably, immunization experiments in rabbits and mice revealed that induced antibodies, like patient autoantibodies, preferentially bound to the most N-terminal domains of THSD7A.<b>Conclusions</b> Our data show that the immune response in THSD7A-associated MN is polyreactive and that autoantibodies predominantly target the most N-terminal part of THSD7A.
We conclude that THSD7A tissue staining of kidney biopsies with membranous nephropathy is a sensitive and specific method for the diagnosis of THSD7A-associated membranous nephropathy and it correlates strongly with the serum antibody testing.