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Insulitis is classified as 15 CD45+ cells per islet in a minimum of three islets ( In humans, roughly 20-30% of insulin-containing islets have been shown to exhibit insulitis compared to 2.9% in insulin-deficient islets ( 3 The genetic landscape of T1D: from risk scores to functional pathways Predisposition to T1D is caused by genetic susceptibility in multiple loci, including INS , IFIH1 , and the class I and II HLA genes ( 3.1 T1D-associated genes: impact on immune function Approximately 40-50% of the genetic risk of developing T1D is attributed to the class I and II MHC/HLA region, with class II being the most significant, as it is essential to the adaptive immune system ( Figure 1 ) ( HLA-DR , HLA-DQ , and HLA-DP loci ( HLA-DPB1 locus also contributes to risk, though its effect is less profound than the DR and DQ loci, with DPB1*0301 and DPB1*0202 associated with risk and DPB1*0402 acting as a protective allele in DR3 carrying patients ( After the HLA genes, the INS locus confers the highest genetic risk of developing T1D ( Figure 1 ) ( INS gene and the 11p15.5 genetic regionharboring the INS and the INS-IGF2 genesrespectively ( IDDM2 locus, which corresponds to the allelic variation at the INS variable number of tandem repeats (VNTR) ( INS gene and proinsulin protein in the thymus and lower expression in the pancreas of human patients harboring the class III allele compared to class I expression