CTLA4-Ig in B7-1-positive diabetic and non-diabetic kidney disease.
Authors Bassi R, Fornoni A, Doria A, Fiorina P
Submitted By Alessia Fornoni on 4/4/2016
Status Published
Journal Diabetologia
Year 2016
Date Published 1/1/2016
Volume : Pages 59 : 21 - 9
PubMed Reference 26409459
Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease in
the Western world. Standard treatments have ultimately proven ineffective in
blocking DKD progression, thus necessitating the design of new therapies to
complement glycaemic and blood pressure control. High glucose levels upregulate
the immune-related molecule B7-1 in podocytes, and such an event may play a
relevant role in DKD onset, suggesting that B7-1 is a suitable therapeutic
target for DKD. CTLA4-Ig is a clinically available fusion protein, approved for
the treatment of some autoimmune diseases, which binds B7-1 and blocks its
signalling. We have previously demonstrated that CTLA4-Ig restores the
physiological structure and cellular motility of podocytes challenged with high
glucose in vitro and abrogates the onset of proteinuria in murine models of DKD
in vivo. Notably, these beneficial effects occurred independently of any
systemic immunological effects of CTLA4-Ig. While the expression of B7-1 on
podocytes raises questions regarding the very nature of the podocyte as we know
it, the preliminary positive effect of CTLA4-Ig on proteinuria in preclinical
models and the evidence of B7-1 expression in kidney biopsies of diabetic
individuals suggest a potential novel indication for CTLA4-Ig in DKD.
Nonetheless, recent reports of problems with detecting podocyte B7-1 and of
inconsistent therapeutic efficacy of CTLA4-Ig in proteinuric patients highlight
the necessity to establish uniformly accepted protocols for the detection of
B7-1 and underline the need for randomised trials with CTLA4-Ig in kidney

Investigators with authorship
Alessia FornoniUniversity of Miami - Medical Campus