M L Maia1, C S Pereira1, G Melo2, I Pinheiro1, M A Exley3,4, G Porto2,5, M F Macedo6,7. 1. UniLiPe, IBMC-Institute for Molecular and Cellular Biology, University Porto, Porto, Portugal. 2. Clinical Hematology, CHP-HSA-Santo António General Hospital Porto, Porto, Portugal. 3. University of Manchester, Manchester, UK. 4. Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. 5. BCRIB, IBMC-Institute for Molecular and Cellular Biology and ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal. 6. UniLiPe, IBMC-Institute for Molecular and Cellular Biology, University Porto, Porto, Portugal. fmacedo@ibmc.up.pt. 7. Aveiro Health Sciences Program, University of Aveiro, Aveiro, Portugal. fmacedo@ibmc.up.pt.
Abstract
PURPOSE: Invariant natural killer T (iNKT) cells are CD1d restricted-T cells that react to lipid antigens. iNKT cells were shown to be important in infection, autoimmunity and tumor surveillance. Alterations in the number and function of these cells were described in several pathological conditions including autoimmune and/or liver diseases. CD1d is critical for antigen presentation to iNKT cells, and its expression is increased in liver diseases. The liver is the major organ affected in Hereditary Hemochromatosis (HH), an autosomal recessive disorder caused by excessive iron absorption. Herein, we describe the study of iNKT cells of HH patients. METHODS: Twenty-eight HH patients and 24 control subjects from Santo António Hospital, Porto, were included in this study. Patient's iron biochemical parameters (serum transferrin saturation and ferritin levels) and the liver function marker alanine transaminase (ALT) were determined at the time of study. Peripheral blood iNKT cells were analyzed by flow cytometry using an anti-CD3 antibody and the CD1d tetramer loaded with PBS57. RESULTS: We found a decrease in the percentage and number of circulating iNKT cells from HH patients when compared with control population independently of age. iNKT cell defects were more pronounced in untreated patients, relating with serum ferritin and transferrin saturation levels. No correlation was found with ALT, a marker of active liver dysfunction. CONCLUSIONS: Altogether, our results demonstrate that HH patients have reduced numbers of iNKT cells and that these are influenced by iron overload.
PURPOSE: Invariant natural killer T (iNKT) cells are CD1d restricted-T cells that react to lipid antigens. iNKT cells were shown to be important in infection, autoimmunity and tumor surveillance. Alterations in the number and function of these cells were described in several pathological conditions including autoimmune and/or liver diseases. CD1d is critical for antigen presentation to iNKT cells, and its expression is increased in liver diseases. The liver is the major organ affected in Hereditary Hemochromatosis (HH), an autosomal recessive disorder caused by excessive iron absorption. Herein, we describe the study of iNKT cells of HHpatients. METHODS: Twenty-eight HHpatients and 24 control subjects from Santo António Hospital, Porto, were included in this study. Patient's iron biochemical parameters (serum transferrin saturation and ferritin levels) and the liver function marker alanine transaminase (ALT) were determined at the time of study. Peripheral blood iNKT cells were analyzed by flow cytometry using an anti-CD3 antibody and the CD1d tetramer loaded with PBS57. RESULTS: We found a decrease in the percentage and number of circulating iNKT cells from HHpatients when compared with control population independently of age. iNKT cell defects were more pronounced in untreated patients, relating with serum ferritin and transferrin saturation levels. No correlation was found with ALT, a marker of active liver dysfunction. CONCLUSIONS: Altogether, our results demonstrate that HHpatients have reduced numbers of iNKT cells and that these are influenced by iron overload.
Entities:
Keywords:
Invariant natural killer T cells; hereditary hemochromatosis; iron; lipid
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