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 the initiation of leucocyte migration from blood vessels to sites of local inflammation. The aim of this study was to investigate T-lymphocyte expression 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 of patients with type I diabetes, 14 patients with Graves' disease, and 22 healthy controls. sL-selectin levels were measured by enzyme-linked immunosorbent assay (ELISA) in enlarged groups of subjects in these categories, as well as in patients with long-standing type I diabetes, treated Graves' disease and type II (non-insulin dependent) diabetes. L-selectin levels were also 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 significantly raised in newly diagnosed type I diabetes compared with controls, with intermediate levels in family members, both with and without islet autoantibodies, 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 family members and controls; levels also fell with increasing age in family members. Multiple regression analysis showed that HLA genotype and age were independent determinants of sL-selectin levels. sL-selectin levels are raised at the time of diagnosis of type I diabetes and Graves' disease and appear to be modulated by disease activity, but levels are determined predominantly by HLA-associated genetic susceptibility and age. sL-selectin may provide a late marker of autoimmune destruction of islets and sequential measurement may be useful in monitoring disease activity and the effect of interventions preceding type I diabetes.
Kretowski
A
A
Department of Endocrinology, Medical School, Bialystok, Poland and Diabetes and Metabolism, Division of Medicine, University of Bristol, Bristol, UK.
Gillespie
K M
KM
Bingley
P J
PJ
Kinalska
I
I
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000097:blood; D006650:Histocompatibility Testing; D006801:Humans; D019041:L-Selectin / Q000097:blood*; D008875:Middle Aged; D012995:Solubility
D015415:Biomarkers; D019041:L-Selectin