D-dimer level, in association with humoral responses, negatively correlates with survival of porcine islet grafts in non-human primates with immunosuppression

作者：Kang Hee Jung^*; Lee Haneulnari; Park Eun Mi; Kim Jong Min; Min Byoung Hoon; Park Chung Gyu

来源：Xenotransplantation, 2017, 24(3): UNSP e12299.

DOI：10.1111/xen.12299

• D-dimer
• islets
• non-human primate
• pig
• xenotransplantation

BackgroundSeveral immunosuppression (IS) regimens achieve long-term graft survival in non-human primates (NHPs) after porcine islet transplantation (PITx), but their success rates vary. To understand the mechanism of graft loss, we investigated the relationships between graft survival and humoral or inflammatory responses for maintenance IS in NHPs after PITx.
MethodsIslets purified from adult wild-type pigs were intraportally transplanted into streptozotocin-induced diabetic rhesus monkeys. Three monkeys received an IS regimen without anti-CD154 monoclonal antibody (mAb, transplant [Tpl]-control) and 11 received IS with anti-CD154 mAb (Tpl-aCD154). Blood samples were obtained weekly from the recipients until graft function ceased and weekly from three healthy monkeys (non-Tpl-control) for 6 months. Levels of D-dimer, C-reactive protein (CRP), and anti-Gal1,3Gal (Gal) IgG, IgG1, IgG2, and IgM were measured. Liver biopsy sections were immunostained for fibrin, insulin, and human CD31.
ResultsTpl-control monkeys had higher time-weighted average levels (levels(twavrg)) of anti-Gal IgG (, difference from level at day 0) and D-dimer than Tpl-aCD154 or non-Tpl-control. The levels(twavrg) of anti-Gal IgG, IgG1, IgG2, and IgM did not differ between Tpl-aCD154 and non-Tpl-control. The levels(twavrg) of D-dimer and anti-Gal IgG2 negatively correlated with graft survival. Liver biopsy sections revealed many spots of fibrin deposition inside islet grafts that were well vascularized by human CD31-positive cells. Level of D-dimer positively correlated with anti-Gal IgG1 in Tpl-control and with anti-Gal IgG2 in Tpl-aCD154.
ConclusionsIntravascular coagulation, in association with immune responses against xenografts, may partly contribute to loss of islet grafts in NHPs after PITx.

• 出版日期2017-6