Triple islet autoantibody–positive type 1 diabetes in Japanese stiff-person syndrome despite a protective HLA haplotype

Type 1 diabetes is a recognized complication of stiff-person syndrome (SPS), yet its immunogenetic determinants in non-European populations remain poorly characterized. A 39-year-old Japanese woman with a 14-year history of SPS presented with diabetic ketoacidosis and was found to have autoimmune type 1 diabetes with rapid beta-cell loss despite long-term immunosuppression. Anti-GAD65 titers were persistently ≥2000 U/mL by enzyme immunoassay, with anti-IA-2 at 8.2 U/mL and anti-ZnT8 at 53.1 U/mL. Urinary C-peptide declined from 4.16 μg/day (SI: 1.38 nmol/day) to <0.9 μg/day (SI: <0.3 nmol/day) over 13 months, indicating rapid progression to near-complete beta-cell failure. High-resolution human leukocyte antigen (HLA) typing revealed a susceptibility haplotype DRB1*04:05-DQA1*03:03-DQB1*04:01, a protective haplotype DRB1*15:02-DQA1*01:03-DQB1*06:01, and HLA-A*24:02; DRB1*03:01, the allele most strongly associated with SPS in European cohorts, was absent. This case demonstrates that SPS-associated autoimmunity can override protective HLA haplotypes, resulting in triple islet autoantibody–positive type 1 diabetes with an immunogenetic profile distinct from that reported in European cohorts.