Q:

1/18/2013
What is the relationship of elevated IgE & iron deficiency anemia (negative skin testing)?

A:

Thank you for your inquiry.

I am not aware of any reported direct relationship between iron deficiency anemia and elevated IgE. In fact, when one looks at the animal studies in the literature designed to assess the effect of iron deficiency anemia on cytokines controlling IgE, the results, as you can see from the abstracts copied below, are inconclusive and at times contradictory. Thus, as best I can tell, there is no direct relationship between iron deficiency anemia and elevated IgE has been demonstrated.

However, the two occurring together can suggest the presence of parasites. Not because the iron deficiency anemia and the elevated IgE are casually related, but because parasitosis can cause both as evidenced by many studies; one of these can be reviewed here.

Thus, in summary, I am not aware of any direct cause and effect relationship between iron deficiency anemia and elevated IgE or vice versa. However, the two can occur together in parasitosis.

Thank you again for your inquiry and we hope this response is helpful to you.

Nutr Res. 2012 Feb;32(2):107-15. doi: 10.1016/j.nutres.2011.12.005.
Iron deficiency reduces serum and in vitro secretion of interleukin-4 in mice independent of altered spleen cell proliferation.
Kuvibidila SR, Velez M, Gardner R, Penugonda K, Chandra LC, Yu L.
Source
Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
Abstract
Iron deficiency, a worldwide public health problem in children and adult women, impairs innate and cell-mediated immunity including interferon-¦Ã secretion. Its effects on interleukin (IL)-4 have not been well investigated. Interleukin-4, a cytokine primarily secreted by TH2 lymphocytes, regulates B-cell proliferation and the switching of immunoglobulin (Ig)M to IgE subtypes; the latter is involved in the defense against helminth infection. Considering the fact that interferon-¦Ã is a potent inhibitor of IL-4, we hypothesize that iron deficiency would increase the secretion of IL-4 and IgE. We measured IL-4 in serum and supernatant of concanavalin A and anti-CD3 antibody-treated spleen cells from iron-deficient, control, pair-fed DBA and C57BL/6 mice (20-24/group) and iron-replete mice for 3, 7, and 14 days (8-13/group). Feeding the low-iron diet (5 ppm vs 50 ppm for the control diet) for 2 months significantly reduced the mean levels of hemoglobin, hematocrit, liver iron stores, thymus weight, and induced splenomegaly in both strains of mice (P < .001). Iron deficiency, and not pair-feeding, reduced plasma IL-4 levels (P < .05), although it did not significantly affect IgE levels. Iron deficiency, especially when associated with thymus atrophy, reduced in vitro IL-4 secretion by activated spleen cells, cell proliferation, and percentage of CD4⁺IL-4⁺ cells (P < .05). Impaired cell proliferation did not fully explain reduced in vitro IL-4 secretion because iron-deficient mice with a normal thymus weight had a normal (3)H-thymidine uptake but decreased supernatant IL-4. It was likely due to low percentage of CD4⁺IL-4⁺. Iron repletion improved IL-4 measurements. Data suggest that iron deficiency has generalized negative effects on T-cell function. Unaltered plasma IgE may be due to other cytokines (ie, IL-13) that also modulate its secretion.

J Cell Biochem. 2003 Oct 1;90(2):278-86.
Effects of iron deficiency on the secretion of interleukin-10 by mitogen-activated and non-activated murine spleen cells.
Kuvibidila S, Yu L, Ode D, Velez M, Gardner R, Warrier RP.
Source
Department of Pediatrics, Division of Research, Louisiana State University Health Sciences Center, Research Institute for Children, 1542 Tulane Avenue, New Orleans, Louisiana 70112, USA.
Abstract
Interleukin (IL)-10 plays crucial regulatory roles in immune responses by inhibiting the secretion of several cytokines (IL-2, IL-12, interferon-gamma (IFN-gamma)) and lymphocyte proliferation. Iron deficiency, a public health problem for children, alters these immune responses. To determine whether these changes are related to altered IL-10 secretion, we measured IL-10 in 24 and 48 h supernatant of spleen cell cultures from iron deficient (ID), control (C), pairfed (PF), and ID mice fed the control diet (iron repletion) for 3 (R3) and 14 (R14) days (d, n = 12/group). Mean levels of hemoglobin, hematocrit, and liver iron stores varied as follows: C approximately equal PF approximately equal R14 > R3 > ID (P < 0.01). Mean baseline IL-10 levels of ID mice tended to be higher than those of other groups (P > 0.05, ANOVA). Mean IL-10 levels secreted by concanavalin A (Con A) and antibody raised against cluster of differentiation molecule 3 (anti-CD3)-treated cells (+/-background) were lower in ID than in C (48 h) and iron replete mice (P < 0.05). Underfeeding also reduced IL-10 secretion by anti-CD3-treated cells (48 h, P < 0.05). Lymphocyte proliferative responses to anti-CD3 +/- anti-CD28 antibodies were lower in ID than in C and PF mice, and they were corrected by iron repletion (P < 0.05). IL-10 levels negatively correlated with indicators of iron status (r <="" 0.05).="" data="" suggest="" that="" iron="" deficiency="" has="" a="" generalized="" deleterious="" effect="" on="" cells="" secrete="" both="" cytokines.="" reduced="" il-10="" secretion="" by="" activated="" does="" not="" overcome="" the="" inhibition="" of="" due="" to="" other="" factors="" t="" cell="" activation="" are="" regulated="" iron.

Cytokine. 2010 Dec;52(3):230-7. doi: 10.1016/j.cyto.2010.08.004. Epub 2010 Sep 17.
Iron deficiency, but not underfeeding reduces the secretion of interferon-gamma by mitogen-activated murine spleen cells.
Kuvibidila SR, Gardner R, Velez M, Yu L.
Source
Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
Abstract
Interferon-gamma (IFN-¦Ã), a cytokine primarily secreted by T and natural killer cells regulates cell-mediated and innate immunity. Iron deficiency, a public health problem in children impairs immune function. To determine whether reduced IFN-¦Ã contributes to impaired immunity, we measured IFN-¦Ã in supernatants of activated (2.5 ¦Ìg/ml concanavalin A, 50 ng/ml anti-CD3 antibody) spleen cells from control (C), iron-deficient (ID), pair-fed (PF), and iron-replete mice for 3 (R3) and 14 days (R14) (11-12/group). Except for iron content, the low iron (5 ppm) and control (50 ppm) diets had identical composition. Mean indices of iron status after 51 days of feeding were as follows: C=PF¡ÖR14>R3>ID (p<0.01). Iron deficiency, but not pairfeeding reduced IFN-¦Ã concentration in mitogen-treated cells by 30-43% (p<0.05); iron repletion improved it. Reduced IFN-¦Ã was not simply due to differences in IL-12 (IFN-¦Ã inducer), percentage of CD3+ T cells, or impaired cell proliferation because these indices were not always decreased. It was likely due to a defect in T cell activation that leads to IFN-¦Ã gene expression. IFN-¦Ã positively correlated with indicators of iron status, body, and thymus weights (r=0.238-0.472; p<0.05). Reduced IFN-¦Ã secretion during iron deficiency may affect response to infections

Nutr Res. 2012 Feb;32(2):107-15. doi: 10.1016/j.nutres.2011.12.005.
Iron deficiency reduces serum and in vitro secretion of interleukin-4 in mice independent of altered spleen cell proliferation.
Kuvibidila SR, Velez M, Gardner R, Penugonda K, Chandra LC, Yu L.
Source
Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
Abstract
Iron deficiency, a worldwide public health problem in children and adult women, impairs innate and cell-mediated immunity including interferon-¦Ã secretion. Its effects on interleukin (IL)-4 have not been well investigated. Interleukin-4, a cytokine primarily secreted by TH2 lymphocytes, regulates B-cell proliferation and the switching of immunoglobulin (Ig)M to IgE subtypes; the latter is involved in the defense against helminth infection. Considering the fact that interferon-¦Ã is a potent inhibitor of IL-4, we hypothesize that iron deficiency would increase the secretion of IL-4 and IgE. We measured IL-4 in serum and supernatant of concanavalin A and anti-CD3 antibody-treated spleen cells from iron-deficient, control, pair-fed DBA and C57BL/6 mice (20-24/group) and iron-replete mice for 3, 7, and 14 days (8-13/group). Feeding the low-iron diet (5 ppm vs 50 ppm for the control diet) for 2 months significantly reduced the mean levels of hemoglobin, hematocrit, liver iron stores, thymus weight, and induced splenomegaly in both strains of mice (P < .001). Iron deficiency, and not pair-feeding, reduced plasma IL-4 levels (P < .05), although it did not significantly affect IgE levels. Iron deficiency, especially when associated with thymus atrophy, reduced in vitro IL-4 secretion by activated spleen cells, cell proliferation, and percentage of CD4⁺IL-4⁺ cells (P < .05). Impaired cell proliferation did not fully explain reduced in vitro IL-4 secretion because iron-deficient mice with a normal thymus weight had a normal (3)H-thymidine uptake but decreased supernatant IL-4. It was likely due to low percentage of CD4⁺IL-4⁺. Iron repletion improved IL-4 measurements. Data suggest that iron deficiency has generalized negative effects on T-cell function. Unaltered plasma IgE may be due to other cytokines (ie, IL-13) that also modulate its secretion.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology