Analysis of natural killer cell functions in patients with hereditary hemochromatosis

Hereditary hemochromatosis (HH) is an autosomal-recessive disorder of the iron metabolism. Patients are typically affected by dysregulated iron levels, which can lead to iron accumulation within essential organs, such as liver, heart and pancreas. Furthermore, many HH patients are also afflicted by several immune defects and increased occurrence of autoimmune diseases that are linked to human homeostatic iron regulator protein (HFE) in the immune response. Here we examined immune cell phenotype and function in 21 HH patients compared to 21 healthy controls with a focus on Natural Killer (NK) cells. We observed increased basal and stimulated production of pro-inflammatory cytokines such as IL-1β or IL-18 in HH patients compared to healthy controls. However, we did not find major changes in the phenotype, the amount or the cytotoxic function of NK cells in HH patients. Instead, our data show a general decrease in the total number of granulocytes in HH patients (2774 ± 958 per μl versus 3457 ± 1122 per μl in healthy controls). These data demonstrate that NK cells of HH patients are not significantly affected and that the patients’ treatment by regular phlebotomy is sufficient to avoid systemic iron overload and its consequences to the immune system

The importance of the general practitioner as an information source for patients with hereditary haemochromatosis

Objective To explore hereditary haemochromatosis (HH) patients’ perspectives on genetic information, namely the types of sources used, preferred or trusted. Methods A survey online was conducted by the European Federation of Associations of Patients with Haemochromatosis (EFAPH) and applied to members of nine National Associations. Results From a total of 1019 validated questionnaires, 895 respondents had performed a genetic testing for HH. From these, 627 self-declared that they were sufficiently informed about the implications of the genetic test to their health. The majority (66%) obtained the information from a specialist doctor, but would like to obtain it from the family doctor. However, the specialist was still the one they trusted more (69%). Regarding the 298 respondents who did not feel sufficiently informed, the majority (78%) also would like to have information from the family doctor although they also trusted the specialist more (75%). A different perspective was reported when patients were asked about the implications of the genetic testing to their family members, where the majority of respondents preferred obtaining information from a specialist (69%). Conclusion This study elucidates the patients’ needs for information and identifies the general practitioner (GP) as the preferred source to obtain information about HH. Practice implications These results may have important implications in future strategies for HH awareness, giving a special emphasis on GPs as the main players

Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles

Analysis of Natural Killer cell functions in patients with hereditary hemochromatosis

Hereditary hemochromatosis (HH) is an autosomal-recessive disorder of the iron metabolism. Patients are typically affected by dysregulated iron levels, which can lead to iron accumulation within essential organs, such as liver, heart and pancreas. Furthermore, many HH patients are also afflicted by several immune defects and increased occurrence of autoimmune diseases that are linked to human homeostatic iron regulator protein (HFE) in the immune response. Here we examined immune cell phenotype and function in 21 HH patients compared to 21 healthy controls with a focus on Natural Killer (NK) cells. We observed increased basal and stimulated production of pro-inflammatory cytokines such as IL-1β or IL-18 in HH patients compared to healthy controls. However, we did not find major changes in the phenotype, the amount or the cytotoxic function of NK cells in HH patients. Instead, our data show a general decrease in the total number of granulocytes in HH patients (2774 ± 958 per μl versus 3457 ± 1122 per μl in healthy controls). These data demonstrate that NK cells of HH patients are not significantly affected and that the patients’ treatment by regular phlebotomy is sufficient to avoid systemic iron overload and its consequences to the immune system

Diagnosis of hereditary hemochromatosis in the era of genetic testing

Background Homozygous C282Y mutation in HFE gene is responsible for the majority of hereditary hemochromatosis cases. Since 1996 this mutation can be identified by a simple genetic test. Aims To determine the clinical presentations in patients with homozygous HFE C282Y mutation and the impact of genetic testing on the time needed for diagnosis. Methods A total of 414 patients diagnosed with C282Y homozygous hereditary hemochromatosis before and after the introduction of genetic testing were evaluated regarding symptoms and clinical findings at diagnosis as well as first hemochromatosis-related clinical features in their past medical history. Results At the time of diagnosis, the predominant symptom was joint pain, in particular of the hands/wrists. Those patients presenting with hand/wrist arthralgia had significantly higher ferritin levels than patients without this joint involvement (p = 0.0005 for males and p\0.0001 for females). After the introduction of the HFE genetic test an earlier diagnosis after first onset of hemochromatosis-associated clinical features was observed between 2006 and 2009 vs. 2000–2005 p = 0.01). Conclusions Arthralgia, in particular of the hands/wrists, is a hallmark of hereditary hemochromatosis and its presence is associated with higher ferritin levels. Despite the availability of a genetic test, it often takes more than 6 years from the first onset of clinical features to diagnose hereditary hemochromatosis. This underlines the importance of raising the awareness of hemochromatosis and its typical clinical presentations

The importance of the general practitioner as an information source for patients with hereditary haemochromatosis.

International audienceOBJECTIVE: To explore hereditary haemochromatosis (HH) patients' perspectives on genetic information, namely the types of sources used, preferred or trusted. METHODS: A survey online was conducted by the European Federation of Associations of Patients with Haemochromatosis (EFAPH) and applied to members of nine National Associations. RESULTS: From a total of 1019 validated questionnaires, 895 respondents had performed a genetic testing for HH. From these, 627 self-declared that they were sufficiently informed about the implications of the genetic test to their health. The majority (66%) obtained the information from a specialist doctor, but would like to obtain it from the family doctor. However, the specialist was still the one they trusted more (69%). Regarding the 298 respondents who did not feel sufficiently informed, the majority (78%) also would like to have information from the family doctor although they also trusted the specialist more (75%). A different perspective was reported when patients were asked about the implications of the genetic testing to their family members, where the majority of respondents preferred obtaining information from a specialist (69%). CONCLUSION: This study elucidates the patients' needs for information and identifies the general practitioner (GP) as the preferred source to obtain information about HH. PRACTICE IMPLICATIONS: These results may have important implications in future strategies for HH awareness, giving a special emphasis on GPs as the main players

Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype.

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles