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D‐dimer level, in association with humoral responses, negatively correlates with survival of porcine islet grafts in non‐human primates with immunosuppression
Author(s) -
Kang Hee Jung,
Lee Haneulnari,
Park Eun Mi,
Kim JongMin,
Min ByoungHoon,
Park ChungGyu
Publication year - 2017
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12299
Subject(s) - immunosuppression , islet , antibody , transplantation , immunology , immune system , biology , medicine , insulin
Background Several immunosuppression ( IS ) regimens achieve long‐term graft survival in non‐human primates ( NHP s) after porcine islet transplantation ( PIT x), 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 NHP s after PIT x. 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‐ CD 154 monoclonal antibody ( mA b, transplant [Tpl]‐control) and 11 received IS with anti‐ CD 154 mA b (Tpl‐ aCD 154). 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‐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 (levels twavrg ) of Δanti‐Gal IgG (Δ, difference from level at day 0) and D‐dimer than Tpl‐ aCD 154 or non‐Tpl‐control. The levels twavrg of Δanti‐Gal IgG, IgG1, IgG2, and IgM did not differ between Tpl‐ aCD 154 and non‐Tpl‐control. The levels twavrg of D‐dimer and Δanti‐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 CD 31‐positive cells. Level of D‐dimer positively correlated with Δanti‐Gal IgG1 in Tpl‐control and with Δanti‐Gal IgG2 in Tpl‐ aCD 154. Conclusions Intravascular coagulation, in association with immune responses against xenografts, may partly contribute to loss of islet grafts in NHP s after PIT x.