Evaluating the Prognostic Value of Islet Autoantibody Monitoring in Islet Transplant Recipients with Long-Standing Type 1 Diabetes Mellitus.

Roi Anteby,Ling-Jia Wang,Aaron Lucander,Laurencia Perea,Gabriela S Generette,Piotr J Bachul,Karolina Golab,Damian Grybowski,John Fung,Lindsay Basto,Piotr Witkowski,Jordan Pyda,Celeste Thomas,Martin Tibudan

doi:10.3390/jcm10122708

Abstract

(1) Background: The correlation between titers of islet autoantibodies (IAbs) and the loss of transplanted islets remains controversial. We sought to evaluate the prognostic utility of monitoring IAbs in diabetic patients after islet transplantation (ITx); (2) Methods: Twelve patients with Type 1 diabetes mellitus and severe hypoglycemia underwent ITx. Serum concentration of glutamic acid decarboxylase (GAD), insulinoma antigen 2 (IA-2), and zinc transport 8 (ZnT8) autoantibodies was assessed before ITx and 0, 7, and 75 days and every 3 months post-operatively; (3) Results: IA-2A (IA-2 antibody) and ZnT8A (ZnT8 antibody) levels were not detectable before or after ITx in all patients (median follow-up of 53 months (range 24–61)). Prior to ITx, GAD antibody (GADA) was undetectable in 67% (8/12) of patients. Of those, 75% (6/8) converted to GADA+ after ITx. In 67% (4/6) of patients with GADA+ seroconversion, GADA level peaked within 3 months after ITx and subsequently declined. All patients with GADA+ seroconversion maintained long-term partial or complete islet function (insulin independence) after 1 or 2 ITx. There was no correlation between the presence of IAb-associated HLA haplotypes and the presence of IAbs before or after ITx; (4) Conclusions: There is no association between serum GADA trends and ITx outcomes. IA-2A and ZnT8A were not detectable in any of our patients before or after ITx.

Highlights

Type 1 diabetes mellitus (T1D) results from the T lymphocyte-mediated destruction of insulin-producing β-cells in the pancreatic islets of Langerhans, B lymphocytes and autoantibodies play
Given the integral role of neutrophils and T cells in disease pathogenesis, we evaluated the effect of inhibiting leukocyte and lymphocyte trafficking via the CXCR1 and CXCR2 inhibitor Reparixin on islet graft failure and insulin-independence
T1D is commonly managed via exogenous insulin administration, some patients are unable to maintain appropriate glycemic control and require islet engraftment to avoid long-term diabetes-related complications

Summary

Introduction

Type 1 diabetes mellitus (T1D) is a widespread economically and socially significant autoimmune disorder [1]. The incidence of T1D is rapidly increasing, with 3–5% more cases each year, and has doubled over the last two decades and the development of more effective and reliable therapies is essential for optimizing patient care but to effectively address the global disease burden [2]. T1D results from the T lymphocyte-mediated destruction of insulin-producing β-cells in the pancreatic islets of Langerhans, B lymphocytes and autoantibodies play 4.0/). A role in islet autoimmunity [3]. Clinical symptoms are preceded by the appearance of autoantibodies targeting islet-related antigens (IAbs). The presence of two or more of the four major islet autoantibodies (IAbs), targeting insulin (IAA), glutamic acid decarboxylase

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