Abatacept and Glomerular Diseases: The Open Road for the Second Signal as a New Target is Settled Down

Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Hernan Trimarchi

Abstract

Glomerulopathy is the third most important cause of kidney disease. Proteinuria is the hallmark of glomerular damage, and a marker of progression of kidney disease, cardiovascular morbidity and mortality. Strategies to reduce proteinuria are partially successful, and despite proteinuria management, renal disease may still progress. Immunosuppression to treat glomerulopathies is nonspecific, partially effective and presents side-effects. It is critical to find safe drugs with specific podocyte molecular targets. Podocytes contain a complex array of proteins. Lymphocyte activation antigen B7-1 (CD80) is located on antigen presenting cells modulating CD4+ and CD8+ T cells by interacting with co-stimulator CD28, a glycoprotein located on T-cells, or with cytotoxic T-lymphocyte protein 4 (CTLA-4) co-inhibitor. Normally, podocytes do not express B7-1. However, certain glomerulopathies are associated with an increase on the surface of podocytes of B7-1, which reduces the ability of podocytes to attach to the surrounding glomerular basement membrane, favouring podocyturia and proteinuria. When the B7-1-CTLA-4 interaction takes place, the immune response is abrogated, while a B7-1-CD28 coupling leads to T cell activation. Abatacept bind...Continue Reading

Citations

Jun 20, 2015·Expert Opinion on Biological Therapy·Domenico SantoroMichele Buemi
May 7, 2016·Journal of Nephropathology·Hernán TrimarchiIris Agorio
Oct 14, 2016·Journal of Translational Medicine·H TrimarchiA Ortiz
Jan 31, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Hernán Trimarchi, Rosanna Coppo
Jun 10, 2019·Archivum Immunologiae Et Therapiae Experimentalis·Ewelina GrywalskaWojciech Załuska
Sep 24, 2020·Genes·Tina LevstekKatarina Trebusak Podkrajsek
May 1, 2021·Journal of Clinical Medicine·Clara Carnicer-CáceresGuillem Pintos-Morell

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