Effects of a new immunosuppressive agent, β-SQAG9, in swine kidney transplantation

We previously reported that 1,2-di-O-acyl-3-O-(-d-sulfoquinovosyl)-glyceride with two stearic acids (β-SQAG9) bound to L-selectin on the cell surface of the CD62L+ T-cell subset and inhibited T-cell migration into lymph nodes in a rat skin allograft model. The aim of this study was to verify the efficacy of β-SQAG9 for kidney allograft survival in miniature swine. Recipient swine underwent bilateral nephrectomy and then received renal allograft transplantation from a swine leukocyte antigen-mismatched donor. Swine were divided into 4 experimental groups. The control (n = 2), 25-SQ (n = 3), FK (n = 3) and 10-SQ/FK (n = 2) groups were treated with no immunosuppressant, 25 mg/kg β-SQAG9, 0.1 mg/kg FK506, and a combination of 10 mg/kg β-SQAG9 and 0.1 mg/kg FK506, respectively, for 14 days. All recipients were autopsied on the day of death to evaluate the cause of death histopathologically. In the control group, the grafts survived for 12 and 15 days. By comparison with the control, β-SQAG9 alone did not contribute to prolongation of graft survival (9, 10 and 24 days), whereas the FK group had significantly longer graft survival (19, 20 and 68 days, p = 0.0289). The 10-SQ/FK pigs died of lethal visceral hemorrhage, although the grafts were still functioning. In conclusion, our results suggest that β-SQAG9 possesses an insufficient immunosuppressive effect for kidney allografts in miniature swine, and may affect blood coagulation and fibrinolysis. In addition, the combination of β-SQAG9 and FK506 can potentially cause severe hemorrhagic complications.