Astrid Weins, MD, PhD

Neptune Ancillary Studies Grant Award

Astrid Weins, MD, PhD, is an Associate Pathologist at Brigham and Women’s Hospital in Boston, MA, and an Assistant Professor of Pathology at Harvard Medical School. She is a kidney pathologist attending on the BWH diagnostic renal pathology service since 2011, and also directs an active translational research program studying proteinuric kidney diseases. She has received the 2019 Renal Pathology Society’s Gloria Gallo Research Award for her contributions to understanding podocyte pathobiology and primary podocytopathies, and a 2019 Eleanor and Miles Shore fellowship by Harvard Medical School.

Brigham & Women’s Hospital in Boston, MA

Harvard Medical School

Lay Summary of the Project:

Minimal Change Disease (MCD) and primary/idiopathic FSGS are important pathology diagnoses in adults and children with nephrotic syndrome (NS). Both are characterized by disruption of the filtration slit diaphragm, the final barrier to protein loss formed by specialized kidney cells, the podocytes; hence, we term this group of diseases “podocytopathies”. In contrast to congenital forms, the cause of acquired podocytopathies/NS remains unknown. There is strong evidence pointing to a role of the immune system and a causative factor circulating in the blood; however, its identity has remained elusive. The fact that particular immunosuppressive therapies are often effective in these patients further supports an autoimmune etiology.

Our studies in a substantial subset of adult and pediatric MCD patients have led to the discovery of autoantibodies targeting and removing an essential kidney filter protein. In animal models, similar antibodies cause rapid disassembly of the filtration slit diaphragm and, consequently, massive proteinuria. We can detect and quantify those antibodies in the blood using a specific test (ELISA). Based on our findings in MCD, we hypothesize that the same antibodies are also detectable in some NS patients who progress to FSGS and in some who show rapid proteinuria recurrence in the transplant.

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