Persistence of Allosensitization after Islet Allograft Failure

Abstract

Allosensitization (PRA+) has been reported after discontinuation of immunosuppression (IS) following graft failure (GF) in islet transplant (ITx) recipients. Persistence of PRA+ after GF is unknown. Thirteen ITx alone (IA) and 5 ITx subjects who also received donor CD34+ hematopoietic stem cells (IBM) and developed GF enrolled in the study “Allosensitization After Islet Transplantation.” Panel reactive antibodies (PRA) were measured yearly while having graft function, within 1 year post-GF and yearly after study enrollment. Two subjects who developed GF but remained on mycophenolate mofetil (MMF) for 2 years and 18 subjects with persistent graft function (15 IA and 3 islet after kidney [IAK]) were also evaluated. 80% IBM subjects developed high PRA+ (>89%) (Figure 1a) while 70% IA subjects were PRA+ at enrollment (0.8-6 years post-GF) and 42%-55% were PRA+ throughout follow-up. PRA results were variable (Figure 1b). The 2 subjects taking MMF post-GF and 1 subject who required IVIG pre-GF (for parvovirus infection) were not PRA+. Four subjects with persistent graft function by 10 years became PRA+ (2 IA and 2 IAK; Figure 1c). After stopping IS, 70% IA subjects became PRA+ with persistence of PRA (although variable) for at least 10 years post-GF. PRA+ was higher in IBM compared to IA subjects. While receiving IS, PRA+ was minimal. Persistence of PRA+ remains a concern due to potentially prolonged wait list time for subsequent organ transplantation if needed. Disclosure P. Rios: None. D. Baidal: None. N. Padilla: None. A.M. Alvarez Gil: None. S. Madiraju: None. J. Ambut: None. A.M. Mantero: None. S. Messinger Cayetano: None. C. Ricordi: None. R. Alejandro: None.

A Strategy to Simultaneously Cure Type 1 Diabetes and Diabetic Nephropathy by Transplant of Composite Islet-Kidney Grafts

“…I-K protocols usually require up to 10,000 IEQ/kg to achieve insulin independence, and direct islet infusion protocols require much more, often necessitating the use of more than a single donor for each recipient ( 29 , 30 ). This in turn may also increase the risk of allosensitization ( 57 , 58 ).…”