Noninvasive diagnosis of recurrent autoimmune type 1 diabetes after islet cell transplantation

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Laxminarayana KorutlaPrashanth Vallabhajosyula

Abstract

Islet cell transplantation is curative therapy for patients with complicated autoimmune type 1 diabetes (T1D). We report the diagnostic potential of circulating transplant islet-specific exosomes to noninvasively distinguish pancreatic β cell injury secondary to recurrent autoimmunity vs immunologic rejection. A T1D patient with hypoglycemic unawareness underwent islet transplantation and maintained normoglycemia until posttransplant day 1098 before requiring exogenous insulin. Plasma analysis showed decreased donor islet exosome quantities on day 1001, before hyperglycemia onset. This drop in islet exosome quantity signified islet injury, but did not distinguish injury type. However, analysis of purified transplant islet exosome cargoes showed decrease in insulin-containing exosomes, but not glucagon-containing exosomes, indicating selective destruction of transplanted β cells secondary to recurrent T1D autoimmunity. Furthermore, donor islet exosome cargo analysis showed time-specific increase in islet autoantigen, glutamic acid decarboxylase 65 (GAD65), implicated in T1D autoimmunity. Time-matched analysis of plasma transplant islet exosomes in 3 control subjects undergoing islet cell transplantation failed to show changes in...Continue Reading

References

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Citations

Jul 1, 2020·Frontiers in Endocrinology·Stephanie ChidesterPaule V Joseph
Aug 2, 2019·Current Diabetes Reports·Sarita NegiSteven Paraskevas
Dec 17, 2020·Frontiers in Immunology·Haipeng PangZhiguang Zhou
Mar 30, 2021·Frontiers in Endocrinology·Taylor M Triolo, Melena D Bellin
Sep 20, 2019·Lancet·Marie-Christine VantyghemMichael R Rickels
Nov 14, 2020·Journal of Translational Medicine·Kaiyuan XuWenmei Wang
Aug 7, 2021·Cell Reports Methods·Patrick M VanderboomK Sreekumaran Nair
Aug 5, 2020·Signal Transduction and Targeted Therapy·Biting ZhouShu Zheng
Aug 28, 2021·Frontiers in Endocrinology·Jordan MattkeBashoo Naziruddin
Sep 28, 2021·Cell Transplantation·Midhat H Abdulreda, Per-Olof Berggren

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