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Allogeneic islet transplantation with monitoring of islet-specific cellular autoimmunity in a Japanese patient with type 1 diabetes: A case report.

ABSTRACT: Here, we report a case of allogeneic islet transplantation in Japan. A 48-year-old man received intraportal islet transplantation (5,945 islet equivalent/kg), and stabilization of blood glucose levels and suppression of hypoglycemia were achieved. In the present case, we used our original assessment method to detect the responses of the recipient's T cells to islet autoantigens over time to monitor cellular autoimmunity. Other markers could not predict graft dysfunction in advance, but our method detected the activation of islet antigen-specific CD8⁺ T-cell responses before the deterioration of pancreatic β-cell function, indicating the possibility of the non-invasive detection of pancreatic β-cell damage due to recurrent autoimmunity.

SUBMITTER: Chujo D

PROVIDER: S-EPMC9017629 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Allogeneic islet transplantation with monitoring of islet-specific cellular autoimmunity in a Japanese patient with type 1 diabetes: A case report.

Chujo Daisuke D Kurokawa Toshiaki T Kawabe Akitsu A Takahashi Nobuyuki N Inagaki Fuyuki F Shinohara Koya K Hagiwara Shotaro S Edamoto Yoshihiro Y Ohmagari Norio N Hinoshita Fumihiko F Tajima Tsuyoshi T Kajio Hiroshi H Ohtsu Hiroshi H Takemura Nobuyuki N Matsumoto Shinichi S Shimoda Masayuki M

Journal of diabetes investigation 20211217 4

Here, we report a case of allogeneic islet transplantation in Japan. A 48-year-old man received intraportal islet transplantation (5,945 islet equivalent/kg), and stabilization of blood glucose levels and suppression of hypoglycemia were achieved. In the present case, we used our original assessment method to detect the responses of the recipient's T cells to islet autoantigens over time to monitor cellular autoimmunity. Other markers could not predict graft dysfunction in advance, but our metho ...[more]

PMID: 34792297

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Project description:Islet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular islet autoreactivity may be required. Monitoring cellular immune reactivity can be useful to identify factors influencing graft survival and to assess efficacy of immunosuppression.Clinicaltrials.gov NCT00623610.

Project description:Aims/hypothesisWe sought to assess the frequency, determinants and prognosis for future diabetes in individuals with islet autoimmunity and whether these factors differ depending on the age of onset of islet autoimmunity.MethodsA prospective cohort (n = 2547) of children from the general population who had a high-risk HLA genotype and children who had a first-degree relative with type 1 diabetes were followed for up to 21 years. Those with the persistent presence of one or more islet autoantibodies were categorised as early-onset (<8 years of age, n = 143, median 3.3 years) or late-onset (≥8 years of age, n = 64, median 11.1 years), and were followed for a median of 7.4 and 4.7 years, respectively. Progression to diabetes was evaluated by Kaplan-Meier analysis with logrank test. Factors associated with progression to diabetes were analysed using the parametric accelerated failure time model.ResultsChildren with late-onset islet autoimmunity were more likely to be Hispanic or African-American than non-Hispanic white (p = 0.004), and less likely to be siblings of individuals with type 1 diabetes (p = 0.04). The frequencies of the HLA-DR3/4 genotype and non-HLA gene variants associated with type 1 diabetes did not differ between the two groups. However, age and HLA-DR3/4 were important predictors of rate of progression to both the presence of additional autoantibodies and type 1 diabetes. Late-onset islet autoimmunity was more likely to present with a single islet autoantibody (p = 0.01) and revert to an antibody-negative state (p = 0.01). Progression to diabetes was significantly slower in children with late-onset islet autoimmunity (p < 0.001).Conclusions/interpretationA late onset of islet autoimmunity is more common in African-American and Hispanic individuals. About half of those with late-onset islet autoimmunity progress to show multiple islet autoantibodies and develop diabetes in adolescence or early adulthood. Further investigation of environmental determinants of late-onset autoimmunity may lead to an understanding of and ability to prevent adolescent and adult-onset type 1 diabetes.

Dataset Information

Allogeneic islet transplantation with monitoring of islet-specific cellular autoimmunity in a Japanese patient with type 1 diabetes: A case report.

Publications

Allogeneic islet transplantation with monitoring of islet-specific cellular autoimmunity in a Japanese patient with type 1 diabetes: A case report.

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