The failure of the glomerular filtration barrier, predominantly due to a loss of slit diaphragm architecture, is at the root of nephrotic syndrome in minimal change disease. The cause was still unknown. Because of the success of B cell–targeted therapy in some patients, as well as the known proteinuric impact of anti-nephrin antibodies in rat models, researchers hypothesized that nephrin autoantibodies could be present in patients with minimal change in illness. They looked for circulating nephrin autoantibodies in sera from patients with minimal change disease in the Nephrotic Syndrome Study Network (NEPTUNE) cohort and from our institutions using indirect ELISA and immunoprecipitation of full-length nephrin from human glomerular extract or a recombinant purified extracellular domain of human nephrin. They also used immunofluorescence to look for podocyte-associated punctate IgG colocalizing with nephrin in renal samples from their institutions. 

They found circulating nephrin autoantibodies during active illness that were considerably decreased or eliminated following treatment response in a subpopulation of patients with minimal change disease in two separate patient cohorts. In renal biopsies from the institutions, they found the autoantibodies together with podocyte-associated punctate IgG. They also found a patient with steroid-dependent childhood minimal change illness who advanced to end stage renal disease; she had a significant post-transplant recurrence of proteinuria, which was related with high pretransplant circulating nephrin autoantibodies.

The identification of nephrin autoantibodies in a subgroup of adults and children with minimal change illness was consistent with previous animal research and adds to the evidence for an autoimmune etiology. They propose a novel molecular categorization of nephrin antibody minimal change illness to serve as a foundation for the development of precision therapies for these patients.

Reference:jasn.asnjournals.org/content/33/1/238

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