title: Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of metalloproteinases, TIMP-1, are elevated in patients with autoimmune thyroid disorders: relevance to vascular inflammation.
abstract: Serum levels of ICAM-1 (Inter Cellular Adhesion Molecule-1), VCAM-1 (Vascular cell Adhesion Molecule-1-I), TIMP-1 (tissue inhibitor of metalloproteinases 1) and MMP-9 (Metalloproteinase 9) are well established markers of inflammation. The physiopathological link between inflammation, atherosclerosis and autoimmunity is well demonstrated. However, serum levels of these biomarkers in patients with autoimmune-mediated dysthyroidism, including their evolution after improvement of the thyroid disorder have not been assessed. So, we evaluated the circulating levels of these markers in autoimmune and in non-autoimmune-mediated dysthyroid patients, and their evolution after treatment of thyroid disease. We conducted a prospective study to evaluate these markers before and after treatment in hyperthyroid patients (n = 33; 28 patients with autoimmune disease), hypothyroid patients (n = 38; 33 patients with autoimmune disease) and euthyroid subjects (n = 33). At baseline, serum levels of ICAM-1, VCAM-1 and TIMP-1 were significantly elevated in patients with hyperthyroidism as compared to euthyroid and hypothyroid patients (respectively p = 0.0005 and p < 0.0001). In multivariate analysis, the differences remained significant for VCAM-1 and TIMP-1. Median levels of ICAM-1, VCAM-1 and TIMP-1 were significantly higher in patients with autoimmune-mediated dysthyroidism compared to euthyroid patients (respectively p < 0.0001 and p = 0.002). In hyperthyroid patients, ICAM-1, VCAM-1 and TIMP-1 concentrations fell significantly after they had become euthyroid (respectively p = 0.0006; p < 0.0001 and p = 0.0009), although VCAM-1 values remained higher than those observed in the control group (p = 0.005). We found that autoimmune-mediated dysthyroidism were associated with increased peripheral blood concentrations of VCAM-1, ICAM-1 and TIMP-1. Whether these biological abnormalities translate into increase intima remodelling and atherosclerosis remains to be studied.
authors.affiliation: Service d'Endocrinologie-Métabolisme, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. christel.jublanc@psl.aphp.fr
authors.forename: C
authors.initials: C
authors.lastname: Jublanc
authors.forename: J L
authors.initials: JL
authors.lastname: Beaudeux
authors.forename: F
authors.initials: F
authors.lastname: Aubart
authors.forename: M
authors.initials: M
authors.lastname: Raphael
authors.forename: R
authors.initials: R
authors.lastname: Chadarevian
authors.forename: M J
authors.initials: MJ
authors.lastname: Chapman
authors.forename: D
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: E
authors.initials: E
authors.lastname: Bruckert
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000097:blood*; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000276:immunology; D007037:Hypothyroidism / Q000097:blood / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013959:Thyroid Diseases / Q000097:blood / Q000276:immunology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1