Subject(s)
Acquired Immunodeficiency Syndrome/complications , Choroid Diseases/etiology , Ocular Hypotension/etiology , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/drug therapy , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Choroid Diseases/diagnosis , Choroid Diseases/drug therapy , Coloring Agents , Eye Diseases/etiology , Fluorescein Angiography , Glucocorticoids/therapeutic use , Humans , Indocyanine Green , Male , Methylprednisolone/therapeutic use , Middle Aged , Ocular Hypotension/diagnosis , Ocular Hypotension/drug therapy , Prednisolone/analogs & derivatives , Prednisolone/therapeutic use , Tomography, Optical Coherence , Viral Load , Vitreous Body/pathologyABSTRACT
BACKGROUND: Tissue factor (TF) expression on islets can result in an instant blood-mediated inflammatory reaction (IBMIR) that contributes to early islet loss. We tested whether peritransplant protection of islets from IBMIR with a monoclonal anti-TF antibody (CNTO859) would enhance engraftment in our nonhuman primate marginal mass model. METHODS: Each of six pairs of cynomolgus monkeys (CM) with streptozotocin-induced diabetes was closely matched for metabolic control and was transplanted with 5,000 IEQ/kg allogeneic, ABO-compatible islets from the same donor under the cover of steroid-free immunosuppression. For each pair, experimental animals received islets cultured with 20 microg/mL anti-TF and were dosed with 6 mg/kg anti-TF intravenously, 10-25 min before islet infusion; control monkeys received an equal number of islets from the same preparation cultured without anti-TF and no in vivo treatment. RESULTS: Early fasting C-peptide (CP) values were different between (P<0.01), but not within, pairs and correlated with in vitro functional capacity of islets as assessed by perifusion (r=0.60; P=0.022). Compared to their matched controls, experimental animals had decreased posttransplant markers of coagulation, higher fasting CP levels (1 month posttransplant and end of study) and prolonged graft function. CONCLUSIONS: These data suggest that pretreatment of islets and the recipient with anti-TF may limit the effects of IBMIR, thereby enhancing islet engraftment and survival.