CD80 and CD86 Expression Patterns and the Capacity of Belatacept to Saturate CD86 in Vitro in Adult and Pediatric Whole Blood

Purpose: Belatacept is a novel co-stimulatory blocker approved for prophylaxis of organ rejection in adult recipients of kidney transplants. It is a fully-human fusion protein that binds to CD80 and CD86, and blocks the CD28 co-stimulation pathway to prevent T-cell activation. CD28 is a co-stimulatory molecule expressed on T cells that binds CD80 and CD86 on antigen presenting cells. In general, CD86 is constitutively expressed on APCs and upon stimulation is rapidly up-regulated, whereas CD80 requires stimulation for expression on the surface of most APCs. This study evaluated and compared CD80 and CD86 expression on monocytes, B cells and myeloid dendritic cells (mDC), as well as belatacept binding to CD86, in adult and pediatric whole blood. Methods: Blood samples were obtained from pediatric patients (age 4-17 yrs) with chronic kidney disease and normal adult volunteers. Expression of CD80 and CD86 was evaluated using a whole blood flow cytometry-based assay. CD86 binding was assessed using a receptor competition assay. Statistical significance was calculated with a twosample unequal variance t-test. Results: CD80 and CD86 expression patterns were comparable between pediatric and adult blood samples. CD86 was expressed at high levels on monocytes and mDC and at very low levels on B cells in both pediatric and adult samples. However, the mean percentage of CD86+ mDC was higher in pediatric patients (69.0±10.0% SD) compared to adults (51.8±12.0% SD, P< 0.001). CD80 was expressed at low levels on monocytes and mDCs, and at slightly higher levels on B cells in pediatric patients and adults. CD80 expression in all cells was much lower overall than expression of CD86.Table: [CD80 and CD86 receptor levels in whole blood]Belatacept-mediated CD86 receptor saturation on monocytes in whole blood was similar between pediatric patients (IC50 = 0.340±0.250 μg/mL) and adults (IC50 = 0.220±0.190 μg/mL). Conclusion: Expression patterns of CD86 and CD80 were comparable between pediatric and adult blood samples. Belatacept binding to CD86 was similar in pediatric and adult blood samples, thereby supporting the investigation of belatacept therapy for pediatric renal transplant recipients.