China
Africa
Explore chapters and articles related to this topic
Major histocompatibility complex
Published in Gabriel Virella, Medical Immunology, 2019
Ellen Klohe, Janardan P. Pandey
High (iron) Fe (HFE) protein is another nonclassical HLA molecule encoded by a gene close to the HLA-A locus. The α chain protein structure is similar to class I molecules and it binds β2-microglobulin. However, the HFE binding groove is predicted to be too small to accommodate peptides. HFE binds the transferrin receptor and is involved in iron adsorption.
Haematology
Published in Michael McGhee, A Guide to Laboratory Investigations, 2019
Haemochromatosis is part of the differential diagnosis in the investigation of abnormal LFT. All first-degree relatives of patients with haemochromatosis should be screened for the disease by genetic testing for the HFE genotype.
Case 71
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
A full history is mandatory. The additional history required is his alcohol intake (alcohol can raise the serum ferritin) and whether there is a relevant family history. Hereditary haemochromatosis is due to mutations in the high Fe (HFE) gene and is inherited in an autosomal recessive fashion. In the United Kingdom, it is often seen in individuals of Irish heritage. Hepcidin is a protein synthesized by the liver which lowers the levels of ferroportin present on the portal vein border of intestinal cells. It therefore serves to reduce iron absorption. Hepcidin also reduces release of iron from macrophages to transferrin. HFE, hemojuvelin (HJV) and the minor transferrin receptor 2 TFR2 all control hepcidin synthesis; mutations in any of the corresponding genes can lower hepcidin secretion and lead to iron overload.
Platelet counts in HFE p.C282Y/p.C282Y and wt/wt post-screening clinical evaluation participants
Published in Platelets, 2023
James C. Barton, J. Clayborn Barton, Ronald T. Acton
Hemochromatosis in whites of western European descent is associated with homozygosity for p.C282Y (exon 4, c.845 G>A; rs1800562), a common missense allele of the HFE gene (homeostatic iron regulator, chromosome 6p22.2).1,2 HFE, a non-classical class I major histocompatibility complex protein, is an upstream regulator of hepcidin and thus of iron homeostasis.3 Laboratory phenotypes of many adults at diagnosis of HFE p.C282Y/p.C282Y include elevated levels of transferrin saturation (TS) and serum ferritin (SF).4 Adults with p.C282Y/p.C282Y have increased risks to develop iron overload and resulting complications, including arthropathy, diabetes mellitus, hypogonadotropic hypogonadism, hepatic cirrhosis, and cardiomyopathy.4 Severe iron overload and cirrhosis due to hemochromatosis occur predominantly in men.4,5 Non-HFE alleles and environmental factors modify iron loading in adults with hemochromatosis.2,4,6
Hereditary hemochromatosis: data from a single center Copenhagen cohort
Published in Scandinavian Journal of Gastroenterology, 2022
Rikke Therkildsen, Eva Efsen Dahl, Frank Vinholt Schiødt
Retrospectively, patients with HH, not previously diagnosed at other centers, from the years 2009 to 2020 were included. Diagnosis was based on genotype. Biochemical data symptoms and signs were recorded following systematic interviews at presentation by one of the authors of this manuscript. The HFE gene was analyzed at Rigshospitalet, Copenhagen, a national biochemical and genetic center. Patients were followed at the HH outpatient clinic at Bispebjerg Hospital, an urban area of Copenhagen. The population in the hospital recruitment area is approximately 270,000 people. Patients were primarily referred from the general practitioner, the blood banks, rheumatologists, fertility centers, or after family follow-up; however, referral patterns were not systematically recorded. A plan for phlebotomies was scheduled according to national guidelines [17]. Phlebotomies were performed weekly in the early years 2009–2012, and from 2013 every two weeks at the clinic by experienced nurses until ferritin was <100 ug/L. The every-two-week phlebotomy program was easier to comply with for the patients.
Oral ferroportin inhibitor vamifeport for improving iron homeostasis and erythropoiesis in β-thalassemia: current evidence and future clinical development
Published in Expert Review of Hematology, 2021
John Porter, Ali Taher, Vip Viprakasit, Antonis Kattamis, Thomas D Coates, Maciej Garbowski, Franz Dürrenberger, Vania Manolova, Frank Richard, M. Domenica Cappellini
The effects of vamifeport have been evaluated in several animal disease models (Table 3). The selection of doses tested in the preclinical models was based on dose-optimization pilot studies in the respective models. A murine model of hereditary hemochromatosis (HFE C282Y) was used to determine the impact of vamifeport on serum and organ iron concentrations. This disease is a result of mutations in genes encoding components that regulate iron homeostasis through the hepcidin–ferroportin axis, causing excessive intestinal absorption of dietary iron and pathological iron overload. Mice fed a low-iron diet were dosed with vamifeport 40 or 110 mg/kg along with stable iron isotope (58Fe) in the drinking water, with the concentration adjusted to 250 ppm iron content to correspond to the iron intake of a standard rodent diet. At the end of the study period, vamifeport had resulted in the correction of serum iron to the levels of wild-type mice and prevented iron retention in the livers of the hemochromatosis mice [51,53].