Malignant gliomas in older adults with poor prognostic signs. Getting nowhere, and taking a long time to do it.

OBJECTIVE

Posttransplant type 1 diabetes (T1D) is typically attributed to transferred donor autoimmunity. We investigated a distinct etiology in a patient who developed diabetes following haploidentical hematopoietic cell transplantation, assessing whether autoimmunity originated from donor or residual host cells.

RESEARCH DESIGN AND

METHODS

Leveraging HLA disparity between the haploidentical donor and recipient, we used HLA class II tetramers to enumerate islet-specific CD4+ T cells in peripheral blood restricted by shared versus recipient-only HLA alleles.

RESULTS

Tetramer analysis revealed an expanded population of islet-specific T cells in the recipient. The donor showed no such expansion. Despite 99% donor T-cell chimerism, >80% of the islet-specific T cells were restricted by recipient-unique HLA alleles, suggesting they originated from the residual host fraction.

CONCLUSIONS

T1D in this patient was most likely driven by residual recipient-derived T cells. Their survival despite myeloablative conditioning and repeated immunotherapy underscores the remarkable durability of established islet autoimmunity.