Highly sensitivity adhesion molecules detection in hereditary haemochromatosis patients reveals altered expression.
Several abnormalities in the immune status of patients with hereditary haemochromatosis (HH) have been reported, suggesting an imbalance in their immune function. This may include persistent production of, or exposure to, altered immune signalling contributing to the pathogenesis of this disorder. Adhesion molecules L-, E- and P-Selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) are some of the major regulators of the immune processes and altered levels of these proteins have been found in pathological states including cardiovascular diseases, arthritis and liver cancer. The aim of this study was to assess L-, E- and P-Selectin, ICAM-1 and VCAM-1 expression in patients with HH and correlate these results with HFE mutation status and iron indexes. A total of 139 subjects were diagnosed with HH (C282Y homozygotes = 87, C282Y/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 healthy control subjects with no HFE mutation (N/N), 18 normal subjects heterozygous for the H63D mutation served as age-sex-matched controls. We observed a significant decrease in L-selectin (P = 0.0002) and increased E-selectin and ICAM-1 (P = 0.0006 and P = 0.0059) expression in HH patients compared with healthy controls. This study observes for the first time that an altered adhesion molecules profile occurs in patients with HH that is associated with specific HFE genetic component for iron overload, suggesting that differential expression of adhesion molecules may play a role in the pathogenesis of HH.
Norris
S
S
Hepatology Research Division and Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, Dublin, Ireland.
White
M
M
Mankan
A K
AK
Lawless
M W
MW
D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000097:blood*; D019040:E-Selectin / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007501:Iron / Q000378:metabolism; D019041:L-Selectin / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D019007:P-Selectin / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
D015815:Cell Adhesion Molecules; D019040:E-Selectin; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D007501:Iron