HLA-A*24 Carrier Status and Autoantibody Surges Posttransplantation Associate With Poor Functional Outcome in Recipients of an Islet Allograft

Abstract

OBJECTIVE We investigated whether changes in islet autoantibody profile and presence of HLA risk markers, reported to predict rapid β-cell loss in pre–type 1 diabetes, associate with poor functional outcome in islet allograft recipients. RESEARCH DESIGN AND METHODS Forty-one patients received ≥2.3 million β-cells/kg body wt in one to two intraportal implantations. Outcome after 6–18 months was assessed by C-peptide (random and stimulated), insulin dose, and HbA1c. RESULTS Patients carrying HLA-A*24-positive or experiencing a significant autoantibody surge within 6 months after the first transplantation (n = 19) had lower C-peptide levels (P ≤ 0.003) and higher insulin needs (P < 0.001) despite higher HbA1c levels (P ≤ 0.018). They became less often insulin independent (16% vs. 68%, P = 0.002) and remained less often C-peptide positive (47% vs. 100%, P < 0.001) than recipients lacking both risk factors. HLA-A*24 positivity or an autoantibody surge predicted insulin dependence (P = 0.007). CONCLUSIONS HLA-A*24 and early autoantibody surge after islet implantation associate with poor functional graft outcome.