Soluble L-selectin levels in type I diabetes mellitus: a surrogate marker for disease activity?

L-selectin (CD62L) is a cell adhesion molecule which plays a key role in th e initiation of leucocyte migration from blood vessels to sites of local in flammation. The aim of this study was to investigate T-lymphocyte expressio n of CD62L antigen and serum levels of soluble L-selectin (sL-selectin) in subjects with clinical and preclinical type I diabetes to determine whether they could provide surrogate markers for disease activity. CD62L selectin expression on memory T lymphocytes was studied by cytometric analysis in 22 patients with newly diagnosed type I diabetes, 20 first-degree relatives o f patients with type I diabetes, 14 patients with Graves' disease, and 22 h ealthy controls. sL-selectin levels were measured by enzyme-linked immunoso rbent assay (ELISA) in enlarged groups of subjects in these categories, as well as in patients with long-standing type I diabetes, treated Graves' dis ease and type II (non-insulin dependent) diabetes. L-selectin levels were a lso related to islet autoantibodies, human leucocyte antigen (HLA) genotype and L-selectin T668C gene polymorphisms. L-selectin expression on memory T lymphocytes was reduced in newly diagnosed diabetes and islet autoantibody positive siblings compared with controls. sL-selectin levels were signific antly raised in newly diagnosed type I diabetes compared with controls, wit h intermediate levels in family members, both with and without islet autoan tibodies, and in long-standing type I diabetes. Levels were also raised in patients with untreated Graves' disease. Patients with type II diabetes had sL-selectin levels which did not differ from controls. sL-selectin levels correlated with the presence of diabetes-associated HLA alleles in both fam ily members and controls; levels also fell with increasing age in family me mbers. Multiple regression analysis showed that HLA genotype and age were i ndependent determinants of sL-selectin levels. sL-selectin levels are raise d at the time of diagnosis of type I diabetes and Graves' disease and appea r to be modulated by disease activity, but levels are determined predominan tly by HLA-associated genetic susceptibility and age. sL-selectin may provi de a late marker of autoimmune destruction of islets and sequential measure ment may be useful in monitoring disease activity and the effect of interve ntions preceding type I diabetes.