Analysis of Glomerular B7-1 Staining in Renal Allograft Biopsies.

Abstract

Background: It has been recently published that patients with recurrent focal segmental glomerulosclerosis in association with B7-1 immunostaining on podocytes may have a clinical response to abatacept (NEJM, 2013). Abatacept was able to stabilize β1-integrin activation in podocytes and reduce proteinuria in patients with B7-1-positive glomerular disease. However, prevalence of positive B7-1 staining in renal allografts and a possible role of abatacept in the treatment of proteinuria post-transplantation remains to be explored. Methods: Using a goat anti-human B7-1 (CD80) antibody, we performed immunostaining for B7-1 on frozen sections of 133 clinically indicated kidney transplant biopsies obtained between 2011 and 2012. Ten samples were excluded from the analysis due to the absence of glomeruli. Results: Out of 123 kidney allograft biopsies analyzed, 93 (76%) were negative for B7-1 staining, 15 biopsies (12.1%) showed trace glomerular positivity, 7 had 1+ (5.6%) and 8 had ≥2+ B7-1 staining (6.5%). There were no cases of recurrent FSGS among those 123 cases. All positive glomeruli showed a granular pattern limited to the periphery of the glomeruli, suggesting specific podocyte staining. Four (4) of the 15 patients with B7-1 staining ≥1+ in their biopsies had nephrotic range proteinuria (27%). The predominant pathologic diagnoses among those with B7-1 positivity were transplant glomerulopathy (46%), followed by acute rejection (33%) and acute tubular injury (20%). In addition, 50% of allograft biopsies obtained from patients with nephrotic syndrome stained positive for B7-1 (4 out of 8). Of those 15 B7-1 positive allografts, five grafts were lost (33%) and one patient died after mean 1.2 year follow-up. Conclusions: In our study cohort, B7-1 is expressed at significant levels in about 10% of kidney allograft biopsies, and the predominant pathologic diagnosis is transplant glomerulopathy. Further studies are needed to resolve B7-1 localization in those biopsies, determine variations of expression over time and explore potential benefits of abatacept therapy in improving graft survival in B7-1-positive patients.