predisposes to a delayed antigen spreading of humoral autoimmunity, whereas and are associated with accelerated progression of advanced subclinical autoimmunity in distinct risk groups. The relation of these alleles to the underlying disease process requires further investigation. Their typing should be relevant for the preparation and interpretation of observational and interventional studies in asymptomatic type 1 diabetes.
OBJECTIVEWe investigated whether changes in islet autoantibody profile and presence of HLA risk markers, reported to predict rapid b-cell loss in pre-type 1 diabetes, associate with poor functional outcome in islet allograft recipients.
RESEARCH DESIGN AND METHODSForty-one patients received ‡2.3 million b-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 HbA 1c .
RESULTSPatients carrying HLA-A*24-positive or experiencing a significant autoantibody surge within 6 months after the first transplantation (n 5 19) had lower C-peptide levels (P £ 0.003) and higher insulin needs (P < 0.001) despite higher HbA 1c levels (P £ 0.018). They became less often insulin independent (16% vs. 68%, P 5 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 5 0.007).
CONCLUSIONSHLA-A*24 and early autoantibody surge after islet implantation associate with poor functional graft outcome.The success rate of an intraportal islet graft for achieving insulin independence critically hinges on the amount of donor tissue implanted (1). However, a positive outcome can be counteracted by other factors, including preexisting autoreactive T cells, HLA alloantibodies, or high lymphocyte counts (2-4). In recipients of a sufficiently large intraportal islet allograft (5,6), we investigated whether the presence of HLA-A*24, HLA-DQ2/DQ8, or rising islet autoantibody levels, previously shown to independently predict rapid b-cell loss in prediabetes (7,8), associates with poor functional graft outcome.
RESEARCH DESIGN AND METHODS
Transplant ProtocolForty-one patients with C-peptide-negative type 1 diabetes (median age 45 years) with a history of recurrent hypoglycemia and negative for preexisting HLA class I and class II antibodies (4) received $2.3 million b-cells (;4,600 islet equivalents)/kg
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