Autoimmune Conditions in 235 Hemochromatosis Probands withHFEC282Y Homozygosity and Their First-Degree Relatives

Barton, James C.

doi:10.1155/2015/453046

Cited by 12 publications

(8 citation statements)

References 90 publications

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“…The general population prevalence of type 1 diabetes defined as autoimmune beta-cell destruction and absolute insulin deficiency is approximately the same as that of hemochromatosis [ 124 ]. Genes within the MHC are major risk factors for type 1 diabetes [ 125 , 126 ], although diverse autoimmune conditions in 236 nonscreening hemochromatosis probands with p.C282Y homozygosity did not include type 1 diabetes [ 127 ]. In a population study of hemochromatosis and iron overload, it was unclear whether participants with “late-onset type 1 diabetes” had beta-cell autoimmunity [ 128 ].…”

Section: Morbidity and Mortality Of Diabetes In Hfe mentioning

confidence: 99%

Diabetes inHFEHemochromatosis

Barton

Acton

2017

Journal of Diabetes Research

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Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with HFE hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without HFE hemochromatosis is similar. Routine iron phenotyping or HFE genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in HFE hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without HFE hemochromatosis.

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Section: Morbidity and Mortality Of Diabetes In Hfe mentioning

confidence: 99%

Diabetes inHFEHemochromatosis

Barton

Acton

2017

Journal of Diabetes Research

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“…Hence, it is one of the major causes of disability, leading to reduction in life expectance, secondary health complications, and socioeconomic damage [ 14 ]. While the exact mechanism of the initiation of the disease is not known, both environmental and genetic factors have been implicated in RA [ 12 , 15 , 16 ]. As RA is multifactorial and complex, both innate and adaptive immunity drive the progression of the disease.…”

Section: Introductionmentioning

confidence: 99%

Alcohol Consumption in Rheumatoid Arthritis: A Path through the Immune System

Azizov

Zaiss

2021

Nutrients

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Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing TFH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol’s negative effects on the immune system is multivariate. Future studies addressing alcohol and its’ metabolite acetate’s effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.

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“…A recent in vitro study evidenced a difference between wild-type and C282Y HFE proteins in their ability to activate CD8+ T lymphocytes, suggesting that C282Y mutation may confer a stronger cellular immunity response in individuals harboring it [24]. On the other hand, autoimmune conditions are common among HH patients [25].…”

Section: Introductionmentioning

confidence: 99%

Cytokine and Gene Expression Profiling in Patients with HFE-Associated Hereditary Hemochromatosis according to Genetic Profile

et al. 2020

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Background: Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is characterized by downregulation of hepcidin synthesis, leading to increased intestinal iron absorption. Objectives: The objectives were to characterize and elucidate a possible association between gene expression profile, hepcidin levels, disease severity, and markers of inflammation in HFE-associated HH patients. Methods: Thirty-nine HFE-associated HH patients were recruited and assigned to 2 groups according to genetic profile: C282Y homozygotes in 1 group and patients with H63D, as homozygote or in combination with C282Y, in the other group. Eleven healthy first-time blood donors were recruited as controls. Gene expression was characterized from peripheral blood cells, and inflammatory cytokines and hepcidin-25 isoform were quantified in serum. Biochemical disease characteristics were recorded. Results: Elevated levels of interleukin 8 were observed in a significant higher proportion of patients than controls. In addition, compared to controls, gene expression of ζ-globin was significantly increased among C282Y homozygote patients, while gene expression of matrix metalloproteinase 8, and other neutrophil-secreted proteins, was significantly upregulated in patients with H63D. Conclusion: Different disease signatures may characterize HH patients according to their HFE genetic profile. Studies on larger populations, including analyses at protein level, are necessary to confirm these findings.

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Autoimmune Conditions in 235 Hemochromatosis Probands withHFEC282Y Homozygosity and Their First-Degree Relatives

Cited by 12 publications

References 90 publications

Diabetes inHFEHemochromatosis

Diabetes inHFEHemochromatosis

Alcohol Consumption in Rheumatoid Arthritis: A Path through the Immune System

Cytokine and Gene Expression Profiling in Patients with <b><i>HFE</i></b>-Associated Hereditary Hemochromatosis according to Genetic Profile

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