Elevated lymphocyte expression of CLIP is associated with type 1 diabetes and may be a useful marker of autoimmune susceptibility

Type 1 diabetes (T1D) susceptibility in humans and in the non-obese diabetic mouse is linked to MHC class II molecules characterized by an amino acid substitution at position 57 of the beta-chain (nonAspB57). The mechanism whereby nonAspB57 MHC molecules contribute to diabetes susceptibility is not currently known. As CLIP is displaced from MHC class II molecules upon peptide binding, if nonAspB57 haplotypes are associated with high CLIP expression, this may reflect a defect in peptide loading. Non-obese diabetic mice have higher mononuclear cell CLIP expression than non-diabetes prone strains, raising the question of whether humans with T1D also exhibit increased CLIP levels. We therefore sought to test whether subjects with T1D have higher levels of leukocyte CLIP expression. Cell surface expression of CLIP was measured on lymphocytes and monocytes using a FITC-conjugated antibody against human CLIP (Pharmingen). Leukocyte CLIP expression was significantly higher in the blood of T1D patients compared to non-diabetic controls. Increased CLIP expression was not a secondary effect of hyperglycemia as CLIP expression was not increased in subjects with type 2 diabetes. This confirms that elevated CLIP expression is a feature of T1D and may be a useful marker for T1D susceptibility.