Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes

Savilahti, E; Rantanen, Ville; Lin, Jing; Karinen, Sirkku; Saarinen, Kimmo; Goldis, Marina; Mäkelä, Mika J.; Hautaniemi, Sampsa; Savilahti, Erkki; Sampson, Hugh A.

doi:10.1016/j.jaci.2010.03.025

Cited by 138 publications

(159 citation statements)

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“…Food-specific IgG values may reflect exposure to a specific food [5]. In support of our results, decreased IgE levels were associated with elevated levels of IgG antibodies against milk in individuals who had developed a tolerance to cow’s milk after experiencing an allergy to the same product [17], and subjects drinking milk had higher levels of milk IgG in their sera than did non-milk drinkers in one study [18]. …”

Section: Discussionsupporting

confidence: 76%

IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population

2012

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BackgroundPatients with Irritable Bowel Syndrome (IBS) often relate their symptoms to the intake of food and modify their diet. IgE-mediated food allergy is uncommon in IBS, but the role of IgG-mediated food hypersensitivity remains inconclusive. The primary aim of this study was to compare food- and yeast-specific IgG and IgG4 antibodies in subjects with and without IBS.MethodsThis was a case control study in the general population for which subjects completed questionnaires about abdominal complaints and their intake of common food items. Blood samples were collected, and food- and yeast-specific IgG and IgG4 antibodies were measured. Antibodies were measured in mg/L.ResultsWe included 269 subjects with IBS and 277 control subjects. After correction for subject characteristics and diet, there were no significant differences with regard to food- and yeast-specific IgG and IgG4 antibodies between subjects with IBS and controls. Lower values of IgG antibodies against egg (OR 0.99 (0.98 to 1.00), p = 0.002) and beef (OR 0.75 (0.60 to 0.94), p = 0.012) and higher values of IgG antibodies against chicken (OR 1.14 (1.03 to 1.27), p = 0.009) were associated with more severe symptoms.ConclusionsOur findings suggest that IgG-and IgG4-mediated food and yeast hypersensitivity in IBS is unlikely. IgG antibodies against food and yeast may reflect the diet.

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Section: Discussionsupporting

confidence: 76%

IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population

2012

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“…An intense specific IgE response to CM proteins is associated with the persistence of CMA, whether measured as serum IgE levels to CM [14,15], serum IgE binding to CM peptides [16,17] or as a skin prick test (SPT) to CM [2]. Decreasing CM-specific IgE levels point to recovery whereas constant or increasing levels predict the persistence of allergy [15,18].…”

Section: Introductionmentioning

confidence: 99%

Specific Antibodies in Oral Immunotherapy for Cow's Milk Allergy: Kinetics and Prediction of Clinical Outcome

Savilahti

Kuitunen

Savilahti

et al. 2014

Int Arch Allergy Immunol

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Background: Methods for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. Methods: We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, β-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). Results: Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged. Conclusions: High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.

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“…Additionally, involvement of IgG4 and also IgA antibodies in natural induction of tolerance is supported by reports of increased allergen-specific IgG4 serum levels in patients who spontaneously become tolerant to cow's milk and from findings that these serum levels are maintained and remain higher than those measured from individuals with diagnosed active cow's milk allergies (134,135). Finally, favored production of IgG4 antibodies was recently demonstrated in patients with melanomas and extrahepatic cholangiocarcinomas, suggesting the association of IgG4 antibodies with immune tolerance favored by IL-10-rich environments such as those in tumors (136,137 monocytes/macrophages) different from those bearing IgG receptors; and (vi) desirable pharmacokinetic properties such as fast clearance from circulation, reducing the chance of antibody-neutralizing antibody responses (35,139,140,141).…”

Section: Triggering Protective Immunity With Immunotherapy-the Role Omentioning

confidence: 89%

Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

Karagiannis

Josephs

et al. 2013

Microbiol Spectr

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The pathogenic role of immunoglobulin E (IgE) antibodies in triggering and maintaining allergic inflammation in response to allergens is due to the binding of multivalent allergens to allergen-specific IgEs on sensitized effector cells. These interactions trigger effector cell activation, resulting in release of potent inflammatory mediators, recruitment of inflammatory cells, antigen presentation, and production of allergen-specific antibody responses. Since its discovery in the 1960s, the central role of IgE in allergic disease has been intensively studied, placing IgE and its functions at the heart of therapeutic efforts for the treatment of allergies. Here, we provide an overview of the nature, roles, and significance of IgE antibodies in allergic diseases, infections, and inflammation and the utility of antibodies as therapies. We place special emphasis on allergen-IgEFcε receptor complexes in the context of allergic and inflammatory diseases and describe strategies, including monoclonal antibodies, aimed at interrupting these complexes. Of clinical significance, one antibody, omalizumab, is presently in clinical use and works by preventing formation of IgE-Fcε receptor interactions. Active immunotherapy approaches with allergens and allergen derivatives have also demonstrated clinical benefits for patients with allergic diseases. These treatments are strongly associated with serum increases of IgE-neutralizing antibodies and feature a notable redirection of humoral responses towards production of antibodies of the IgG4 subclass in patients receiving immunotherapies. Lastly, we provide a new perspective on the rise of recombinant antibodies of the IgE class recognizing tumor-associated antigens, and we discuss the potential utility of tumor antigen-specific IgE antibodies to direct potent IgE-driven immune responses against tumors.

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Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes

Cited by 138 publications

References 31 publications

IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population

IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population

Specific Antibodies in Oral Immunotherapy for Cow's Milk Allergy: Kinetics and Prediction of Clinical Outcome

Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment

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