Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecules relate to cell invasion of autoimmune thyroid disease. We studied plasma soluble P-Selectin (platelet activation-dependent granule-external membrane protein), E-Selectin (endothelial leukocyte adhesion molecule) and L-Selectin (leukocyte endothelial cell adhesion molecule-1) levels in patients with Graves' disease before and during methimazole treatment. Plasma P-, E- and L-Selectin levels in patients with untreated Graves' disease were significantly higher than those in normal subjects. Plasma P-Selectin levels decreased when their thyroid functions were normal for more than 6 months after the start of methimazole treatment. No significant change in plasma E- and L-Selectin levels in patients with Graves' disease was found between hyperthyroid state and euthyroid state after the start of methimazole treatment, but plasma L-Selectin levels in patients with untreated Graves' disease were significantly lower than those in the patients in the first euthyroid state. There was no significant correlation between plasma P-Selectin levels and serum FT4 levels, nor between plasma P-Selectin levels and serum FT3 levels. These results suggested that thyroid hormones might reflect expression of P-, L- and E-Selectin from endothelial cells, or lymphocytes, or platelets in patients with Graves' disease.
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PMID:Plasma selectin levels in patients with Graves' disease. 907 11

Adhesion molecules, such as Intercellular Adhesion Molecule-1 (ICAM-1), play an important role during the autoimmune process of Graves' disease (GD). So the objective of the study was to evaluate the time-course of the soluble ICAM-1 (sICAM-1) in GD. Concentrations of sICAM-1, thyroid hormones and TSAb (thyroid-stimulating antibodies) were determined in sera from 30 healthy controls, 41 untreated GD patients and after 3, 6, 12, 18 months of carbimazole therapy (no.=30), at relapse (no.=11) or 2 years after the end of therapy when remission (no.=13). Mean sICAM-1 concentration was significantly higher in untreated GD patients than in controls (mean+/-SD: 371+/-108 ng/ml vs 243+/-47 ng/ml, p<0.0001) until 6 months of therapy (289+/-102 ng/ml; NS). The number of positive patients (sICAM-1 levels>mean of the controls+2 SD) declined from 56% (23/41) at the time of the diagnosis to 10% (3/29) at 18 months. At relapse, mean sICAM-1 level significantly increased compared to that at 18 months of therapy (288+/-65 vs 236+/-59 ng/ml, p=0.005). At remission mean sICAM-1 level was significantly lower than in relapse patients (240+/-48 ng/ml, p=0.04); no patient displayed sICAM-1 positive values. In conclusion, sICAM-1 concentrations were increased in sera of newly diagnosed GD patients, declined significantly during carbimazole therapy and could again be increased at relapse. sICAM-1 could reflect an ongoing immune process and help to affirm the presence of an autoimmunity notably in some cases of TSAb negative patients. However its precise interest in clinical practice remains to be determined in further studies.
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PMID:Longitudinal study of soluble intercellular adhesion molecule-1 (ICAM-1) in sera of patients with Graves' disease. 1043 52

Graves' ophthalmopathy (GO) is thought to result from a complex interplay of genetic and environmental factors. Various genes, including those coding for HLA, may determine a patient's susceptibility to the disease and its severity, but in addition, numerous and often unknown environmental factors may determine its course. Once established, the chronic inflammatory process within the orbital tissues appears to take on a momentum of its own. Based upon our current state of knowledge, we propose the working scheme shown in Fig. 1 for the pathogenesis of GO: Against the background of a permissive immunogenetic milieu, circulating T cells in patients with Graves' Disease (GD), directed against certain antigens on thyroid follicular cells, recognize antigenic epitopes that are shared by tissues contained in the orbital space. Here, preadipocytes and fibroblasts most likely act as target and effector cells of the orbital immune process. This includes preadipocyte fibroblasts present in the perimysium of extraocular muscles, which do not appear to be immunologically or metabolically different from those located in the orbital connective tissue. Differentiation of orbital preadipocyte fibroblasts into mature adipocytes expressing increased levels of TSHR may be driven by stimulation with circulating or locally produced cytokines or effectors. To date, it is still unknown how autoreactive T cells escape deletion by the immune system and become directed against a self-antigen that is presented by cells residing in the thyroid gland and in certain extrathyroidal locations. Mimicry of a host antigen by a microorganism or presentation of an altered self-antigen may promote proliferation and expansion of autoreactive T cell clones. T cell recruitment into the orbital tissues is facilitated by certain chemokines and cytokines, which help to attract T cells by stimulating the expression of several adhesion molecules (e.g. ICAM-1, VCAM-1, CD44) in vascular endothelium and connective tissue cells. Adhesion molecules are known to be important for a variety of interactions between immunocompetent cells, connective tissue cells and extracellular matrix components. In addition, these molecules play a central role in lymphocyte activation and localization, facilitating antigen recognition, T cell costimulation, and various effector-target cell functions at the inflammatory sites, many of which result in amplification of the cellular immune process in active GO. Analysis of variable region genes of T cell antigen receptors in orbital T cells of patients with active GO has revealed limited variability of TcR V gene usage, suggesting that antigen-driven selection and/or expansion of specific T cells may occur during the early stages of GO. T cells and macrophages populate the orbital space and release a number of cytokines (most likely a Th-1-type spectrum) into the surrounding tissues. Cytokines, oxygen free radicals and fibrogenic growth factors, released both from infiltrating inflammatory and residential cells, act upon orbital preadipocytes in a paracrine and autocrine manner to stimulate adipogenesis, fibroblast proliferation, glycosaminoglycan synthesis, and the expression of immunomodulatory molecules. Smoking, a well-known aggravating factor in GO with an uncertain mode of action, may aggravate tissue hypoxia and exert important immunomodulatory effects. Finally, the long-held hypothesis of a thyroid cross-reactive antigen within the orbital tissues has recently gained significant support from an animal model of ophthalmopathy, and from in vitro and ex vivo studies. If confirmed by immunological studies, these data may well explain the localized infiltration of the orbital tissues by autoreactive lymphocytes that share intriguing molecular features with intrathyroidal lymphocytes. Local release of certain cytokines, TSHR-directed autoantibodies, or other factors might further enhance adipogenesis, glycosaminoglycan synthesis and expression of
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PMID:Thyroid-associated eye disease. 1098 Jun 91

Graves' ophthalmopathy (GO) is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles and/or orbital connective tissue. Adhesion molecules play an important role in the initiation and maintenance of the inflammatory immune process. Cellular activation and local expression of adhesion molecules lead to leucocyte recruitment, migration to inflammatory sites and targeting in the extravascular space. Vascular endothelium in retroocular connective tissues of patients with GO is strongly positive for EMAL-1 and VCAM-1, whereas VCAM-1 immunoreactivity is minimal and ELAM-1 immunoreactivity is generally absent in normal retroocular tissue. Interactions between matched activated T lymphocytes and orbital endothelial cells are mediated by integrin dependent ICAM-1/LFA-1 and VCAM-1/VLA-4 pathways and reveal marked differences when comparing GO orbital endothelial cells to normal ones. Higher soluble ICAM-1 volumes in patients with Graves' disease with GO than those in patients with Graves' disease without ophthalmopathy can reflect the degree of inflammatory activity. Increased soluble ELAM-1 concentration only in patients with GO suggests that soluble ELAM-1 could be a specific marker of endothelium activation in GO.
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PMID:[The role od adhesion molecules in the pathogenesis of Graves ophthalmopathy]. 1187 15

Adhesion molecules play a key role in autoimmune disorders, and serum concentrations of soluble adhesion molecules are increased in Graves' ophthalmopathy (GO). Whether this is due to the strong association with smoking is unknown. It is also not known if the severity or activity of GO determine the serum levels of adhesion molecules. We measured serum concentrations of sICAM-1, sVCAM-1 and sELAM-1 in 62 euthyroid Graves' patients with untreated GO, in 62 healthy controls matched for sex, age and smoking habits, and in 26 euthyroid Graves' patients without GO. GO severity was assessed by the Total Eye Score and the activity by the Clinical Activity Score. Adhesion molecules were measured by highly sensitive ELISAs. GO patients had higher levels than controls (median values in ng/ml with range): sICAM-1 300 [171--575] versus 244 [119--674], P < 0.001; sVCAM-1 457 [317--1060] versus 410 [238--562], P < 0.001; and sELAM-1 61 [19--174] versus 53 [23--118], P = 0.021. Euthyroid Graves' disease patients without GO had levels similar to controls: sICAM-1 273 138--453), sVCAM-1 386 [260--1041] and sELAM-1 46 [22--118]. Smoking had an independent effect and was associated with higher levels of sICAM-1 and lower levels of sVCAM-1 in both GO patients and controls; sELAM-1 levels were comparable. In the 62 GO patients, sICAM-1 correlated significantly with severity of eye disease (r = 0.40, P = 0.002). No correlation was found with the duration of GO, the Clinical Activity Score or TBII levels. Multivariate analysis of all 150 subjects showed that the presence of GO and smoking are independent determinants of sICAM-1 and sVCAM-1 concentrations. In GO patients, the Total Eye Score was a stronger determinant than smoking. It is concluded that (i) smoking is associated with increased sICAM-1 and decreased sVCAM-1 levels; (ii) independent from smoking, euthyroid GO patients have higher levels of sICAM-1, sVCAM-1 and sELAM-1 than patients with euthyroid Graves' disease or healthy controls; (iii) the major determinant of sICAM-1 in GO patients is the severity of their eye disease.
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PMID:Smoking and disease severity are independent determinants of serum adhesion molecule levels in Graves' ophthalmopathy. 1187 56

Adhesion molecules are involved in cell invasion in autoimmune thyroid disease. It was also reported that patients with untreated Graves' disease (GD) had high serum level of soluble form of E-selectin (sE-selectin), the concentration of which correlated with the activity of the disease. The aim of the present study was to elucidate whether the common variants in E-selectin gene (SELE) were associated with the development of GD. Six tagSNPs within SELE were studied in 297 patients with GD and 208 healthy subjects in Chinese population. Our data showed that common SELE variants were associated with GD (P=0.012-0.036). Haplotype analysis of the single nucleotide polymorphisms revealed an association of a haplotype ATAACC with GD (P=0.005). Furthermore, quantitative trait analysis showed a significant association of SELE haplotype with sE-selectin levels (P=0.0438). This study therefore could provide us to a certain degree the insight that common SELE variants may be associated with susceptibility to GD in Chinese population, though the limitation of sample size and multiple test problems exists.
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PMID:The common variants of E-selectin gene in Graves' disease. 1809 8

The etiopathogenesis of Graves' disease (GD) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. Adhesion molecules such as intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and E-selectin are secreted from vascular endothelium and promote accumulation of leukocytes in damaged endothelial areas. This study examined the possible association of ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) single nucleotide polymorphisms (SNPs) with the occurrence of GD. ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs in DNA from peripheral blood leukocytes of 171 patients with GD and 259 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. We did not find significant differences in the distributions of studied polymorphisms, nor in the haplotype frequencies between patients with GD and healthy control. However, the anti-TPO levels in E-selectin 128R allele carrying subjects (SR + RR) were higher than S128S genotype (p < 0.05). In addition, the decline of TSH levels was more prominent in ICAM1 469 E carrying subjects (KE + EE) in comparison with wild homozygotes (p < 0.05). Although there is not association between ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs and susceptibility to GD, higher anti-TPO in E-selectin 128 SR + RR, and lower TSH in ICAM1 469 KE + EE subjects suspect that these genotypes are prone to increased antithyroid autoantibody production with more accentuated TSH suppression in GD. Further studies with a larger cohort, analyzing other polymorphisms in ICAM, VCAM1 and E-selectin genes are necessary to support our observations.
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PMID:ICAM1 K469E and E-selectin S128R polymorphisms could predispose to increased autoantibody production and TSH suppression in Graves' disease. 2324 61