The comparison between autoantibody-positive participants who carried HLA-DR4-DQ8 and those with HLA-DR4 but not HLA-DQ8 demonstrated that most features that are associated with DR3/DR4 (e.g. prevalence of IA-2A positivity, dysglycaemia, T1D-GRS2 and risk of progression to type 1 diabetes) were significantly higher in participants with HLA-DR4-DQ8, except for IAA positivity, which was significantly more prevalent in those with HLA-DR4 but not HLA-DQ8. This evidence concerns the gene TNFRSF25 and type 1 diabetes mellitus.