Hepatic damage in C282Y homozygotes relates to low numbers of CD8+ cells in the liver lobuli
Department of Gastroenterology and Hepatology, Karolinska Hospital, Stockholm, Sweden (E. M. P. Cardoso, K. Hagen, R. Hultkrantz); Department of Molecular Pathology and Immunology, Abel Salazar Institute for Biomedical Sciences, Porto, Portugal (M. de Sousa).Correspondence to: Rolf Hultcrantz MD, Department of Gastroenterology and Hepatology, Karolinska Hospital, S-171 76 Stockholm, Sweden. Tel.: + 46–85–1775033; fax: + 46–85–1772637; e-mail: rolfhult@divmed.ks.se
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.
Patients and 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.
Conclusion 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.