Linking iron-deficiency with allergy: role of molecular allergens and the microbiome

Abstract

Atopic individuals tend to develop a Th2 dominant immune response, resulting in hyperresponsiveness to harmless antigens, termed allergens. In the last decade, epidemiological studies have emerged that connected allergy with a deficient iron-status. Immune activation under iron-deficient conditions results in the expansion of Th2-, but not Th1 cells, can induce class-switching in B-cells and hampers the proper activation of M2, but not M1 macrophages. Moreover, many allergens, in particular with the lipocalin and lipocalin-like folds, seem to be capable of binding iron indirectly via siderophores harboring catechol moieties. The resulting locally restricted iron-deficiency may then lead during immune activation to the generation of Th2-cells and thus prepare for allergic sensitization. Moreover, iron-chelators seem to also influence clinical reactivity: mast cells accumulate iron before degranulation and seem to respond differently depending on the type of the encountered siderophore. Whereas deferoxamine triggers degranulation of connective tissue-type mast cells, catechol-based siderophores reduce activation and degranulation and improve clinical symptoms. Considering the complex interplay of iron, siderophores and immune molecules, it remains to be determined whether iron-deficiencies are the cause or the result of allergy.

Atopic Disease and Anemia in Korean Patients: Cross-Sectional Study with Propensity Score Analysis

“…However, several studies presented above confirmed the correlation between atopic disease (atopic dermatitis, asthma, or food allergy) and anemia and/or iron deficiency. This may support the evidence as a result of studies that allergies cause iron deficiency at the molecular levels [47]. The causality of allergic disease and anemia and/or low iron levels cannot be accurately presented at this time, but we would like to suggest that it has an explicit association.…”

NCM 1921, a Mixture of Several Ingredients, Including Fatty Acids and Choline, Attenuates Atopic Dermatitis in 1-Chloro-2,4-Dinitrobenzene-Treated NC/Nga Mice

“…[18][19][20]. The severity of dermatitis and the clinical index of dermatitis were assessed according to a previously reported method [21].…”

AllergoOncology: Microbiota in allergy and cancer—A European Academy for Allergy and Clinical Immunology position paper

“…In atopy, a poor iron status is associated with allergy, whereas an improved status abrogates or seems to prevent the onset of allergy. In cancer, iron contributes to tumor growth with high serum iron increasing the risk of several cancers (Table ) …”

“…Human lipocalins, such as tear lipocalin 1 and lipocalin 2 present in the nasal mucosa, can interfere with bacterial iron sequestration, and may directly modulate site‐specific microbial composition. The immunomodulatory and apoptosis‐regulating properties of LCN2 have been linked to its ability to shuttle iron .…”