Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Introduction: Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for refractory chronic pancreatitis. The mechanisms underlying islet graft loss, however, remain unclear. Interferon gamma-induced protein (IP)-10 or CXCL10 is a chemokine which plays a central role in inflammatory diseases. We determined the role of IP-10 in islet function in autologous transplantation.
Methods: Serum samples collected from 26 TPIAT patients during 24h after islet infusion were analyzed for IP-10 using Luminex assay. Patients were divided into two groups based on high (n =11) or low (n =15) levels of post-transplant IP-10 determined by the area under the curve (AUC) after correction of islet yield (IEQ). Marginal dose of 200 islets isolated from IP-10 knockout B6 mice were transplanted into wild-type diabetic B6 mice. Graft function was determined with post-transplant blood glucose levels.
Results: Among TPIAT patients, IP-10 low group had significantly higher levels of secreted C-peptide compared to the IP-10 high group one-year post-transplant (1.1 ± 0.2 Vs 0.5 ± 0.1 ng/mL; p =0.03) (Figure). We also observed increased amount of exogenous insulin and hemoglobin A1c and decreased SUITO index in IP-10 high group compared to IP-10 low group. In the animal study, 0/6 mice in the control group showed restored normoglycemia, whereas in the mice receiving IP-10-/- islets 4/8 exhibited normoglycemia following 60 days post-transplantation. Comparison of IPGTT curves among the transplant groups showed mice receiving marginal dose of 200 IP-10-/- islets having glucose levels similar to mice receiving full dose of 400 islets from wild type mice.
Conclusions: Together, these data suggested that IP-10 secretion during the peritransplant period can result in poor glycemic control. Inhibition of IP-10, therefore, should be considered for improving islet graft function.
To cite this abstract in AMA style:Kanak M, Lawrence M, Kunnathodi F, Yoshimatsu G, Shahbazov R, Takita M, Levy M, Naziruddin B. Association of IP-10 With Poor Islet Graft Function After Total Pancreatectomy With Islet Autotransplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/association-of-ip-10-with-poor-islet-graft-function-after-total-pancreatectomy-with-islet-autotransplantation/. Accessed December 4, 2020.
« Back to 2015 American Transplant Congress