2392-P: Prevalence of HLA-DRB1*04:01 in U.S. Adults with New-Onset Type 1 Diabetes

Introduction and Objective: HLA-DRB1*04:01 (DRB1*04:01) is a known risk allele, frequently found in non-Hispanic white Type 1 Diabetes (T1D) populations. T1D incidence across the globe has risen along with identification of lower-risk HLAs. The modern prevalence of DRB1*04:01 in the adult onset T1D population is yet to be established. Previous studies reported a prevalence of DRB1*04:01 of up to 39% in T1D Swedish children, and 38.6% of 2674 participants in the BRIDge (BRI, Seattle) study. Here, we aim to determine the prevalence of DRB1*04:01 among new onset adults in a diverse U.S. population. Methods: This ongoing, non-interventional study is enrolling adults aged 18-45 yrs with recent T1D diagnosis at 5 U.S. sites. HLA genotyping is performed on blood using a GenDx NGSgo® MX11-3 next generation sequencing kit. Results: Of the first 18 participants enrolled, 38.9% (n=7) were positive for DRB1*04:01, and 61.1% were negative (n=11), consistent with previously reported data. The median age was 24.5 years (± SD 7.3yrs, range 18-42), with no difference between DRB1*04:01 positive or negative groups and evenly distributed between male and female. Most participants were white (n=16) and non-Hispanic/Latino (n=14). One participant reported Black/African American race, 3 reported Hispanic ethnicity, and 1 was unreported. All DRB1*04:01 positive participants were white and non-Hispanic. Other prevalent genotypes were HLA-DRB1*03:01 (n=6, 33.3%) and HLA-DRB1*01:01 (n=3, 16.7%). Conclusion: Preliminary analysis of new onset T1D participants shows a DRB1*04:01 prevalence of 38.9%, consistent with prior literature. In this cohort, all DRB1*04:01 positive participants were white and non-Hispanic/Latino. Enrollment is ongoing, and future analysis will report DRB1*04:01 prevalence by race and ethnicity. These results will inform deployment of GNTI-122, an autologous engineered Treg cell therapy designed to prevent T1D progression in individuals with new onset T1D, leveraging the presentation of islet specific antigen by the HLA-DRB1*04:01 allele to target Treg cells to the pancreas. Disclosure R. Unger: None. K.R. Klein: Consultant; Current; Roche Pharmaceuticals, Novo Nordisk A/S. Advisory Panel; Current; vTv Therapeutics. Consultant; Current; Antag Therapeutics, Metsera. C. Levy: Research Support; Current; Tandem Diabetes Care, Inc., Novo Nordisk, Abbott Diabetes, MannKind Corporation. Consultant; Current; MannKind Corporation, Tandem Diabetes Care, Inc. Research Support; Current; Deka/Sequel, Dexcom, Inc., Genti Bio. Consultant; Current; Deka/Sequel. S.J. Rancic: None. D. Turculet: None. C.M. Levister: Research Support; Ended; Capillary Biomedical, Inc., Tandem Diabetes Care, Inc. Research Support; Current; DEKA, Sequel. J. Gaglia: Consultant; Current; Vertex Pharmaceuticals Incorporated, AstraZeneca, polTreg. Research Support; Current; Sanofi. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. M. Zhang: None. S. Kateman: None. B. Resnick: None. A.R. Coryell: None. S.E. Gitelman: Advisory Panel; Current; Sanofi, SAB Biotherapeutics, Inc., Eli Lilly and Company, Genentech, Inc. Research Support; Current; Sanofi, SAB Biotherapeutics, Inc., GentiBio. Other - Member, DSMB; Current; Diamyd. Advisory Panel; Current; AnaptysBio, Inc. C. Ellement: None. B.S. Bruggeman: Research Support; Current; GentiBio. S. Peeling: None. J.L. Hosford: Consultant; Ended; GNTI-BIO. V.L. DeVault-Nelson: Employee; Current; GentiBio. D. Gaddis: Other - I am an employee and own options at GentiBio, Inc.; Current; GentiBio, Inc. Other - I was an employee and owned stock at Novartis; Ended; Novartis AG. C.L. Kotynski: None. C. Patel: None. K.M. Neff: None. M.A. Bach: Employee; Current; GentiBio. Employee; Ended; Structure Therapeutics.