ISLET CELL TRANSPLANTS FAIL DUE TO DONOR SPECIFIC ANTIBODIES

LATE BREAKING II

L. Piemonti¹, P.I. Terasaki², M.J. Everly³, P. Maffi¹, S. Mario⁴, A. Secchi¹, C. Massimo⁴, M. Ozawa^3
1, Diabetes Research Institute (HSR-DRI) San Raffaele Scientific Institute, Milano/ITALY, ², Terasaki Foundation Laboratory, Los Angeles/UNITED STATES OF AMERICA, ³, One Lambda Inc, Los Angeles/CA/UNITED STATES OF AMERICA, ⁴Foundation Ca' Granda Ospedale Maggiore Policlinico, Organ and Tissue Transplantation Immunology, Milan/ITALY

Body: Background: To date little is known regarding the impact of human leukocyte antigen (HLA) antibodies on islet cell transplantation. Herein we describe the association between HLA antibodies and outcomes in islet cell transplant patients. Methods: Islet cell transplanted patients between 2001 and 2010 were studied. Prospectively collected sera was serially collected from 44 islet cell recipients from the date of transplant. Of the 44, 39 had recipient typing for A,B, and DR loci and were included in analysis. DQ typing was not conducted on any patient. The mean number of donors per patient was 2.3±1.0. Sera from these 39 patients was tested retrospectively on LABScreen® mixed and LABScreen® single antigen beads (SAB) from One Lambda, Inc (Canoga Park, CA). A positive cutoff for SAB was set at 1000 mean florescence intensity (MFI). All statistics were performed via STATA-MP v.10. A p-value greater than 0.05 was considered significant. Results: Of the 39 islet cell recipients, the median survival from first islet cell infusion was 441 days (16 days to 7.5 years). Insulin independence was achieved in 41% (16/39) of recipients. The median period of insulin independence was 249 days (56 days to 6.9 years). Regarding donor specific HLA (DSA), 17/39 (46%) of the patients were positive post-transplant and was significantly associated with failure (p=0.037). Primarily patients had Class I antibodies (11/39). DR loci DSA was uncommon (3/39). Those who developed DSA were more likely to have multiple donors (p=0.013).

	Failure (n=25) n (%)	Success (n=14) n (%)	p-value
HLA antibodies	20 (80)	13 (93)	NS
DSA (all)	14 (56)	3 (21)	0.037
DSA Class I	10 (40)	1 (7)	0.029
DSA (DR-loci)	1 (4)	2 (14)	NS
DSA Both	3 (12)	0 (0)	NS
DQ antibody	11 (44)	4 (29)	NS

Conclusion: The presence of DSA in islet cell transplantation is highly associated with failure. This data suggests that monitoring for donor specific HLA antibodies in islet cell transplant patients is important and that treatment of these antibodies could benefit outcomes.

Disclosure: All authors have declared no conflicts of interest.