Diabetes and other autoimmune endocrine diseases

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Transfer of Type 1 Diabetes by Bone Marrow Transplantation in Humans: Rare Clinical Cases of a Great Potential for Understanding Disease Pathogenesis

Thursday, June 15
5:45 PM - 7:00 PM

In the early 1990s, a few cases of Type 1 Diabetes (T1D) transfer after allogeneic bone marrow transplantation (BMT) between HLA-identical siblings were reported as case reports but the mechanism responsible for this transfer has never been investigated. We believe that these “accidental experiments” provide the ideal clinical setting to gain insights into T1D pathogenesis.
Two cases of T1D transfer after BMT between HLA-identical adult and paediatric siblings occurred at our Hospital. The adult bone marrow recipient became diabetic 9 years post-transplant while the seven-year-old boy seroconverted one year after transplantation and he is currently T1D-free but 4 T1D-autoAb positive.
To dissect the mechanism of disease transfer we tested whether the same autoAg-specific T cells were present both in the donor and the recipient. Proliferative responses to T1D-associated autoantigens (GAD65 and pro-insulin) were measured by the CFSE dilution assay. The same frequencies of autoreactive T cells proliferating to GAD65 and pro-insulin were present both in donor and recipient while the frequencies of T cells to the recall Ag Tetanus Toxoid were different. Autoreactive T-cell clones were generated and current studies are testing the presence of shared TCR among the donors and the recipients. These rare clinical cases represent a unique opportunity to test the hypothesis that transfer of pathogenic T cells in humans can cause pancreas destruction in the absence of a diabetogenic-specific environmental trigger.

Alessandra Mandelli

San Raffaele Scientific Institute, Diabetes Research Institute

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    Angela Stabilini

    San Raffaele Scientific Institute, Diabetes Research Institute

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      Eleonora Tresoldi

      San Raffaele Scientific Institute, Diabetes Research Institute

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        Maki Nakayama

        University of Colorado, Barbara Davis Center

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          Piermarco Piatti

          San Raffaele Scientific Institute, Diabetes Research Institute

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            Emanuele Bosi

            San Raffaele Scientific Institute, Diabetes Research Institute

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              Manuela Battaglia

              San Raffaele Scientific Institute, Diabetes Research Institute

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