title: Hepatic damage in C282Y homozygotes relates to low numbers of CD8+ cells in the liver lobuli.
abstract: BACKGROUND
  Although most Caucasian patients with hereditary haemochromatosis (HH) show the same mutation in the HFE gene, the phenotypic expression of the disease varies greatly. We have previously shown that patients with HH who have high iron stores have low numbers of circulating CD8+ T lymphocytes.
  
  
  METHODS
  Liver and peripheral blood were studied in 37 C282Y homozygous HH patients; nine normal livers and 11 livers from patients with cirrhosis due to hepatitis C virus or alcoholic liver disease were also investigated. Eleven jejunal biopsies from HH patients and 17 normal biopsies were studied. The numbers of CD8+ cells were determined in peripheral blood by fluorescence-activated cell sorting analysis, and in the liver or small intestine by immunohistochemistry.
  
  
  RESULTS
  In HH patients the number of CD8+ T lymphocytes in peripheral blood correlated significantly with the number of CD8+ cells in the liver lobuli but not with that in the small intestine. Body iron stores correlated negatively with the number of CD8+ T lymphocytes in peripheral blood and in the liver, but not with the number in the small intestine. HH patients with cirrhosis had the lowest CD8+ cell count in liver sections, in contrast with other forms of cirrhosis.
  
  
  CONCLUSIONS
  The results indicate that HH patients with the HFE C282Y mutation and low numbers of CD8+ cells in the liver lobuli have higher iron stores and are more prone to develop liver cirrhosis.
authors.affiliation: Department of Gastroenterology and Hepatology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: E M
authors.initials: EM
authors.lastname: Cardoso
authors.forename: K
authors.initials: K
authors.lastname: Hagen
authors.forename: M
authors.initials: M
authors.lastname: de Sousa
authors.forename: R
authors.initials: R
authors.lastname: Hultcrantz
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D019943:Amino Acid Substitution; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005293:Ferritins / Q000032:analysis; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D000071020:Hemochromatosis Protein; D006485:Hemosiderin / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000032:analysis; D007583:Jejunum / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000032:analysis; D000074019:T-Cell Intracellular Antigen-1
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D005293:Ferritins; D006485:Hemosiderin; D007501:Iron