Iron loading in HFE p.C282Y homozygotes found by population screening: relationships to HLA-type and T-lymphocyte subsets

Thorstensen, Ketil; Kvitland, Mona A.; Irgens, Wenche Ø.; Åsberg, Arne; Borch-Iohnsen, Berit; Moen, Torolf; Hveem, Kristian

doi:10.1080/00365513.2017.1342136

Cited by 3Iron Metabolism and DisordersNeurological diseases and metabolismHemoglobinopathies and Related Disorders

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Iron loading in HFE p.C282Y homozygotes found by population screening: relationships to HLA-type and T-lymphocyte subsets

Thorstensen, Ketil, Kvitland, Mona A., Irgens, Wenche Ø., Åsberg, Arne, Borch-Iohnsen, Berit, Moen, Torolf, Hveem, Kristian·2017·Scandinavian Journal of Clinical and Laboratory Investigation

DOI 10.1080/00365513.2017.1342136

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Abstract

Iron loading in p.C282Y homozygous HFE hemochromatosis subjects is highly variable, and it is unclear what factors cause this variability. Finding such factors could aid in predicting which patients are at highest risk and require closest follow-up. The degree of iron loading has previously been associated with certain HLA-types and with abnormally low CD8 + cell counts in peripheral blood. In 183 Norwegian, p.C282Y homozygotes (104 men, 79 women) originally found through population screening we determined HLA type and measured total T-lymphocytes, CD4 + and CD8 + cells, and compared this with data on iron loading. In p.C282Y homozygous men, but not in homozygous women, we found that the presence of two HLA-A*03 alleles increased the iron load on average by approximately 2-fold compared to p.C282Y homozygous men carrying zero or one A*03 allele. On the other hand, the presence of two HLA-A*01 alleles, in male subjects, apparently reduced the iron loading. In p.C282Y homozygous individuals, the iron loading was increased if the CD8 + cell number was below the 25 percentile or if the CD4 + cell number was above the 75 percentile. This effect appeared to be additive to the effect of the number of HLA-A*03 alleles. Our data indicate that homozygosity for the HLA-A*03 allele significantly increases the risk of excessive iron loading in Norwegian p.C282Y homozygous male patients. In addition, low CD8 + cell number or high CD4 + cell number further increases the risk of excessive iron loading.

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Low numbers of CD8+ T cells and high numbers of CD4+ T cells are associated with a higher degree of iron overload in hereditary hemochromatosis patients.
“Vice versa, low numbers of CD8 + T cells and high numbers of CD4 + T cells are associated with a higher degree of IO in HH patients (Thorstensen et al., 2017).”
From Iron in infection and immunity (2020) · cites this paper as Thorstensen et al., 2017

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Authors: Thorstensen, K., Kvitland, M. A., Irgens, W. Ø., Åsberg, A., Borch-Iohnsen, B., Moen, T., & Hveem, K.
Affiliations: St Olav's University Hospital (NO)
Institute of Basic Medical Sciences, Department of Nutrition, University of Oslo, Oslo, Norway;
Norwegian University of Science and Technology (NO)
Corresponding author: Thorstensen, Ketil
ORCID: Åsberg, Arne
Moen, Torolf
Hveem, Kristian
Venue: Scandinavian Journal of Clinical and Laboratory Investigation
Publisher: Informa UK Limited
Published: 2017-07-05
Volume: 77
Issue: 7
Pages: 477-485
ISSN: 0036-5513 (ISSN-L)
1502-7686
DOI: 10.1080/00365513.2017.1342136
OpenAlex: W2726118716
Cited by: 3
References: 53
Citations by year: 2023: 1 · 2021: 1 · 2020: 1
FWCI: 0.21
Type: journal article
Language: en
Open access: closed
Locations: Scandinavian Journal of Clinical and Laboratory Investigation (publishedVersion)
PubMed (publishedVersion)
Funders: Norwegian University of Science and Technology
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Keywords: hereditary hemochromatosis, iron overload, HLA-A*03, HLA-A*01, CD8+ T cells, CD4+ T cells, T cell subsets, sex differences, mass screening, Norwegian patients
MeSH terms: Hemochromatosis Protein, Alleles, Female, HLA Antigens, Homozygote, Humans, Iron, Male, Mass Screening, Middle Aged, Regression Analysis, Risk Factors, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes

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Iron loading in HFE p.C282Y homozygotes found by population screening: relationships to HLA-type and T-lymphocyte subsets

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