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How Severe Anaemia Might Influence the Risk of Invasive Bacterial Infections in African Children.
Abuga, KM, Muriuki, JM, Williams, TN, Atkinson, SH
International journal of molecular sciences. 2020;(18)
Abstract
Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.
2.
Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or α1-Acid Glycoprotein.
Jorgensen, JM, Yang, Z, Lönnerdal, B, Chantry, CJ, Dewey, KG
The Journal of nutrition. 2017;(6):1194-1199
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Abstract
Background: Ferritin and hepcidin are markers of iron status that typically increase during inflammation or infection. The postpartum period is a physiologically unique life stage in which the relations between these proteins and other markers of inflammation have not been extensively studied.Objective: We aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive protein (CRP) and α1-acid glycoprotein (AGP)] were associated with ferritin or hepcidin in postpartum women in California.Methods: This is a secondary analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP, ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating women. We examined Pearson correlation coefficients between all biomarkers at both time points and differences in mean values of ferritin and hepcidin between those with and without elevated CRP and/or AGP.Results: At 2 and 17 wk postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L, respectively. Neither CRP nor AGP was significantly correlated with ferritin (r = 0.07 and -0.06; n = 114 at 2 wk; -0.14 and -0.14; n = 95 at 17 wk) or hepcidin (r = 0.18 and -0.03 at 2 wk; -0.05 and -0.14 at 17 wk; P > 0.05 for all). At 2 wk, geometric mean plasma ferritin and hepcidin concentrations did not differ between women with and without elevated CRP or AGP (P > 0.5), but at 17 wk women with elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL) compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P = 0.02].Conclusion: Lower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states.
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Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.
Langer, AL, Ginzburg, YZ
Hemodialysis international. International Symposium on Home Hemodialysis. 2017;(Suppl 1):S37-S46
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Abstract
Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development.