D-Dimer Level, in Association with Humoral Responses, Negatively Correlates with Survival of Porcine Islet Grafts in Nonhuman Primates with Immunosuppression.
1Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
2Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea
Meeting: 2017 American Transplant Congress
Abstract number: A145
Keywords: Islets, Pig, Primates, Xenotransplantation
Session Information
Session Name: Poster Session A: Immunosuppression
Session Type: Poster Session
Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Background: Several immunosuppression (IS) regimens achieve long-term graft survival in nonhuman 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.
Methods: Islets 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 from three healthy monkeys (nonTpl-control) for 6 months. Levels of D-dimer, C-reactive protein (CRP), and anti-Galα1,3Gal (Gal) IgG, IgG1, IgG2, and IgM were measured. Liver biopsy sections were immunostained for fibrin, insulin, and human CD31.
Results: Tpl-control monkeys had higher time-weighted average levels (levelstwavrg) of [Delta]anti-Gal IgG ([Delta], difference from level at day 0) and D-dimer than Tpl-aCD154 or nonTpl-control. The levelstwavrg of [Delta]anti-Gal IgG, IgG1, IgG2, and IgM did not differ between Tpl-aCD154 and nonTpl-control. The levelstwavrg of D-dimer and [Delta]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 [Delta]anti-Gal IgG1 in Tpl-control and with [Delta]anti-Gal IgG2 in Tpl-aCD154.
Conclusions: Coagulation activation on the vasculature of porcine islets, in association with immune responses against xenografts, may perpetuate and result in development of microvascular thrombosis in grafts, playing a role in loss of islet grafts in NHPs after PITx.
CITATION INFORMATION: Kang H, Lee H, Park E, Kim J, Min B, Park C.-G. D-Dimer Level, in Association with Humoral Responses, Negatively Correlates with Survival of Porcine Islet Grafts in Nonhuman Primates with Immunosuppression. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Kang H, Lee H, Park E, Kim J, Min B, Park C-G. D-Dimer Level, in Association with Humoral Responses, Negatively Correlates with Survival of Porcine Islet Grafts in Nonhuman Primates with Immunosuppression. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/d-dimer-level-in-association-with-humoral-responses-negatively-correlates-with-survival-of-porcine-islet-grafts-in-nonhuman-primates-with-immunosuppression/. Accessed May 12, 2025.« Back to 2017 American Transplant Congress