Abatacept and Glomerular Diseases: The Open Road for the Second Signal as a New Target is Settled Down.
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 binds to B7-1 by blocking the CD28 or potentiating the CTLA-4 signals. In B7-1 positive podocytes, abatacept may be a specific tool to decrease proteinuria. Selected patents are also briefly presented in this review.
Servicio de Nephrologia, Hospital Britanico de Buenos Aires, Perdriel 74 (1280), Buenos Aires, Argentina. htrimarchi@hotmail.com.
Hernan
H
Trimarchi
D000069594:Abatacept / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D005921:Glomerulonephritis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D010330:Patents as Topic; D011485:Protein Binding; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D007166:Immunosuppressive Agents; D000069594:Abatacept