B7-1 Is Not Induced in Podocytes of Human and Experimental Diabetic Nephropathy

J Am Soc Nephrol. 2016 Apr;27(4):999-1005. doi: 10.1681/ASN.2015030266. Epub 2015 Aug 28.

Abstract

The incidence of progressive kidney disease associated with diabetes continues to rise worldwide. Current standard therapy with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers achieves only partial renoprotection, increasing the need for novel therapeutic approaches. Previous studies described B7-1 induction in podocytes of patients with proteinuria, including those with FSGS and type 2 diabetic nephropathy (DN). These findings sparked great excitement in the renal community, implying that abatacept, a costimulatory inhibitor that targets B7-1, could be a novel therapy for diabetic renal disease. Given previous concerns over the value of B7-1 immunostaining and the efficacy of abatacept in patients with recurrent FSGS after renal transplantation, we investigated B7-1 expression in human and experimental DN before embarking on clinical studies of the use of B7-1 targeting strategies to treat proteinuria in DN. Immunohistochemical analysis of kidney specimens using different antibodies revealed that B7-1 is not induced in podocytes of patients with DN, independent of disease stage, or BTBR ob/obmice, a model of type 2 diabetes. These results do not support the use of abatacept as a therapeutic strategy for targeting podocyte B7-1 for the prevention or treatment of DN.

Keywords: B7–1; diabetic nephropathy; podocyte.

MeSH terms

  • Animals
  • B7-1 Antigen / analysis
  • B7-1 Antigen / biosynthesis*
  • Diabetic Nephropathies / metabolism*
  • Humans
  • Male
  • Mice
  • Podocytes / chemistry
  • Podocytes / metabolism*

Substances

  • B7-1 Antigen