Vaccines can prevent infectious diseases, but their efficacy varies, and factors impacting vaccine effectiveness remain unclear. Iron deficiency is the most common nutrient deficiency, affecting >2 billion individuals. It is particularly common in areas with high infectious disease burden and in groups that are routinely vaccinated, such as infants, pregnant women, and the elderly. Recent evidence suggests that iron deficiency and low serum iron (hypoferremia) not only cause anemia but also may impair adaptive immunity and vaccine efficacy. A report of human immunodeficiency caused by defective iron transport underscored the necessity of iron for adaptive immune responses and spurred research in this area. Sufficient iron is essential for optimal production of plasmablasts and IgG responses by human B-cells in vitro and in vivo. The increased metabolism of activated lymphocytes depends on the high-iron acquisition, and hypoferremia, especially when occurring during lymphocyte expansion, adversely affects multiple facets of adaptive immunity, and may lead to prolonged inhibition of T-cell memory. In mice, hypoferremia suppresses the adaptive immune response to influenza infection, resulting in more severe pulmonary disease. In African infants, anemia and/or iron deficiency at the time of vaccination predict decreased response to diphtheria, pertussis, and pneumococcal vaccines, and response to measles vaccine may be increased by iron supplementation. In this review, we examine the emerging evidence that iron deficiency may limit adaptive immunity and vaccine responses. We discuss the molecular mechanisms and evidence from animal and human studies, highlight important unknowns, and propose a framework of key research questions to better understand iron-vaccine interactions.

UNASSIGNED: Upon re-examination of our human history, evolutionary perspectives, and genetics, a prevailing iron deficiency phenotype appears to have evolved to protect the human race from extinction.
UNASSIGNED: In this review, we summarize the evolutionary and genetic perspectives pointing towards the hypothesis that low iron mitigates infection. The presence of infection promotes the generation of resistance alleles, and there are some evolutionary and genetic clues that suggest the presence of an iron deficiency phenotype that may have developed to protect against infection. Examples include the relative paucity of iron overload genes given the essential role of iron, as well as the persistence of iron deficiency among populations in spite of public health efforts to treat it. Additional examination of geographic areas with severe iron deficiency in the setting of pandemics including H1N1, SARS, and COVID-19 reveals that areas with higher prevalence of iron deficiency are less affected. RNA viruses have several evolutionary adaptations which suggest their absolute need for iron, and this dependency may be exploited during treatment.
UNASSIGNED: RNA viruses pose a unique challenge to modern healthcare, with an average of 2-3 new pathogens being discovered yearly. Their overarching requirements for iron, along with human evolutionary and genetic adaptations which favored an iron deficiency phenotype, ultimately suggest the potential need for iron control in these infections.

BACKGROUND: Anemia is the main extraintestinal comorbidity of Inflammatory Bowel Disease (IBD). Differentiating the type of anemia in these disorders is still a challenge. Hepcidin could be a promising biomarker to identify iron deficiency anemia (IDA), anemia of chronic disease (ACD) and the concomitant presence of both IDA and ACD.
METHODS: To evaluate the potential role of hepcidin dosage in the management of anemia in IBD patients, we performed a systematic review by a comprehensive literature analysis of original papers reporting the dosage of hepcidin in IBD patients. In all the articles reviewed, the dosage of ferritin was reported, and the correlation between hepcidin and ferritin has been used to compare these two biomarkers.
RESULTS: A total of 12 articles concerning the dosage of hepcidin in IBD were included, comprising in total of 976 patients. The results of the hepcidin values in IBD patients when compared with controls were conflicting. In fact, four articles described an increase in this biomarker, three showed a decrease and five did not find significant differences. The correlation with ferritin was positive and significant. In three studies, some differences between hepcidin dosages and ferritin levels indicate a possible role when IDA and ACD could be present at the same time.
CONCLUSIONS: Considering the contradictory data of the studies, the diagnostic role of hepcidin as a biomarker remains elusive in IBD patients. These differences could be due to the clinical characteristics of the patients enrolled that should be better defined in the future. A suitable clinical trial should be designed to outline the possible role of hepcidin in differentiating IDA, ACD and concomitant IDA and ACD in IBD patients. At the moment, ferritin still remains the best marker to diagnose these conditions, in addition to hemoglobin, transferrin saturation and CRP as recommended by the ECCO guidelines.

Iron overload emerges as a serious complication in myelodysplastic syndromes (MDS), particularly associated with frequent transfusions during the course of the disease. The discovery and description of hepcidin\'s mechanisms of action have contributed to a deeper understanding of iron metabolism. The existing literature reports a potential role of hepcidin in MDS, yet these data are fragmented and presented in an unstructured, somewhat chaotic manner. Hence, to address the existing data, we performed a systematic review of observational studies examining hepcidin levels in MDS. An extensive review of three bibliographic databases (Pubmed, Web of Science, and Scopus) enabled us to identify 12 observational studies. These studies focused primarily on adult patients with low-risk MDS who underwent transfusions and chelation therapy. An in-depth analysis of these manuscripts led to four main conclusions: (1) although high serum hepcidin levels are associated with MDS, most studies generally have not found a significant difference in these levels between patients and healthy individuals; (2) serum hepcidin levels are specific to MDS type; (3) serum hepcidin levels in MDS are strongly associated with transfusions and the genetic status of patients; and (4) high-risk MDS is associated with high serum hepcidin levels. While we have furnished a comprehensive summary of the significance of hepcidin in MDS, there are still gaps that future research should address. This pertains primarily to the capacity of hepcidin in predicting adverse outcomes for MDS patients and evaluating the efficacy of chelation therapy or the need for transfusion.

Following a diagnosis of iron deficiency anaemia in pregnancy, iron supplements are prescribed using UK guidelines; however, despite this, the condition remains highly prevalent, affecting up to 30% of pregnant women in the UK. According to the World Health Organisation, it globally accounts for 45% in the most vulnerable groups of pregnant women and infants (<5 years old). Recently, the efficacy of iron replacement therapy and the effectiveness of current standard testing of iron parameters have been reviewed in order to evaluate whether a more accurate diagnosis can be made using alternative and/or supplementary markers. Furthermore, many questions remain about the mechanisms involved in iron metabolism during pregnancy. The most recent studies have shed more light on serum hepcidin and raised questions on the significance of pregnancy related inflammatory markers including cytokines in iron deficiency anaemia. However, research into this is still scarce, and this review aims to contribute to further understanding and elucidating these areas.

OBJECTIVE: This study evaluated the correlation between maternal hepcidin and other biomarkers of iron status, markers of inflammation, and maternal body weight during pregnancy, as well as neurodevelopment in the offspring.
METHODS: PubMed, Web of Science, Scopus, and Embase were searched from inception until March 2022.
METHODS: Studies conducted among pregnant women without apparent pregnancy complications were included. Eligible studies reported correlation coefficients between maternal hepcidin and any outcomes of maternal biomarkers of iron status or inflammatory load during pregnancy, prenatal maternal body weight, and offspring neurodevelopment. Studies without correlation data were eligible if they quantitatively reported volumes of both maternal hepcidin and any marker of iron status and/or inflammatory load during gestation.
METHODS: Pooled correlation coefficients between maternal hepcidin and outcomes of interest were calculated using the Fisher r-to-Z transformation. Both fixed-effects and DerSimonian and Laird random-effects models were used to calculate pooled correlation coefficient. When meta-analysis was not feasible, results were descriptively synthesized.
RESULTS: Forty-six studies with 6624 participants were eligible. Hepcidin was significantly correlated with hemoglobin in the third trimester (r=0.21; 95% confidence interval, 0.1-0.32); ferritin in the first (r=0.31; 95% confidence interval, 0.01-0.61) and third trimester (r=0.35; 95% confidence interval, 0.23-0.48); soluble transferrin receptor in the second trimester (r=-0.27; 95% confidence interval, -0.4 to -0.14); total iron-binding capacity in the second trimester (r=0.37; 95% confidence interval, 0.24-0.50); and serum iron in the third trimester (r=0.11; 95% confidence interval, 0.02-0.19). Hepcidin was significantly correlated with the inflammatory marker interleukin-6 in the third trimester (r=0.26; 95% confidence interval, 0.17-0.34) and C-reactive protein in the second (r=0.16; 95% confidence interval, 0.03-0.30) and third trimester (r=0.28; 95% confidence interval, 0.04-0.52). Four out of 5 studies reported weak-to-moderate positive correlation between hepcidin and body mass index. Hepcidin levels varied across body mass index categories. No single study reported the relationship between maternal hepcidin and neurodevelopment in offspring.
CONCLUSIONS: Hepcidin weakly to moderately correlates with biomarkers of iron and inflammation in pregnancy.

This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity\'s inflammation biomarkers.
Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes.
Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin\'s quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity\'s inflammatory environment began to be published in 2008.
Obesity\'s chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.

Iron deficiency anemia is the most common extraintestinal symptom in patients with colorectal cancer (CRC). Inflammation associated with malignancy leads to functional iron deficiency via the hepcidin pathway, whereas chronic blood loss causes absolute iron deficiency and depletion of iron stores. The assessment and treatment of preoperative anemia is of great importance in patients with CRC, since published data have consistently shown that preoperative anemia is associated with increased need for perioperative blood transfusions and more postoperative complications. Recent studies have documented mixed results regarding the preoperative intravenous iron administration in anemic CRC patients in terms of efficacy for anemia correction, cost-effectiveness, need for transfusions and risk for postoperative complications.

OBJECTIVE: The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this potential relationship through a systematic review of observational studies.
METHODS: An electronic search of three databases, including PubMed, Scopus, and Web of Science Core Collection, was performed up to 31 March 2022. Two independent reviewers assessed the search results according to predetermined inclusion and exclusion criteria, following PRISMA guidelines.
RESULTS: Of the 3607 titles identified, 13 studies published between 2008 and 2021 met the inclusion criteria. Most studies included a moderate number of participants and controls and used enzyme-linked immunosorbent assay (ELISA) to determine serum hepcidin levels. The principal findings: (1) serum hepcidin levels in patients with AL or undergoing HCT are increased compared to controls, regardless of the patient\'s age and the phase of disease treatment; (2) AL therapy and HCT significantly influence serum hepcidin levels; (3) serum hepcidin may predict a worse outcome in patients with AL and post-HCT.
CONCLUSIONS: This systematic review provides an overview of observational studies that deal with the association of hepcidin with AL and HCT. Although disturbances in iron metabolism are common in AL and HCT, and hepcidin seems to play a cardinal role in their modulation, more extensive research is needed.

Tuberculosis (TB) is an airborne illness that induces systemic inflammation. It often affects the lungs causing cough, fever, and chest pain. A commonly associated comorbid condition in TB is anemia. This review article has summarized various studies with an aim to gain a better understanding of pathogenesis and the role of cytokines that contribute to the development of anemia in TB. The study has gathered risk factors that enhance the likelihood of TB patients acquiring anemia. It has reviewed therapeutic modalities such as antitubercular therapy and iron therapy in an attempt to find which of them are effective in reducing the severity of anemia. This review article has also emphasized the importance of measuring hepcidin and ferritin and has touched upon the investigations that can be easily implemented.