Serum IgE and IgG responses to food antigens in normal and atopic dogs, and dogs with gastrointestinal disease

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Abstract

In human food allergy, with or without concurrent atopy, there may be significant increases in serum allergen-specific IgE. Serological methods have been tried but are not currently recommended for diagnosis of suspected food allergy in dogs. The aim of this study was to investigate humoral immune responses to food antigens in dogs. Serum IgG and IgE antibodies specific for food antigens were measured by enzyme linked immunosorbent assay (ELISA) using polyclonal anti-dog IgG and IgE reagents. Antigens tested were beef, chicken, pork, lamb, chicken, turkey, white fish, whole egg, wheat, soybean, barley, rice, maize corn, potato, yeast and cow’s milk. Three groups were examined: normal dogs, dogs with atopic dermatitis (AD); and dogs with one of four types of gastrointestinal (GI) disease: small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), food-responsive disease, and infectious diarrhoea. Statistically significant differences in food-specific antibodies were not detected between the GI subgroups. There were statistically significant differences in the IgE concentration between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested. There were statistically significant differences in the average IgG concentrations between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested, except egg and yeast. The relationship of antigen responses for pooled data was analysed using principle component analysis and cluster plots. Some clustering of variables was apparent for both IgE and IgG. For example, all dogs (normal and diseased) made a similar IgG antibody response to chicken and turkey. Compared with other groups, atopic dogs had more food allergen-specific IgE and this would be consistent with a Th2 humoral response to food antigens. Dogs with GI disease had more food allergen-specific IgG compared with the other groups. This may reflect increased antigen exposure due to increased mucosal permeability which is a recognised feature of canine intestinal disease.

Introduction

In humans, a range of different adverse reactions to food are recognised. These include food allergy which may be defined as an immunologically-mediated, excessive reaction to food substances. Food allergy must be distinguished from food intolerance where non-immunological mechanisms are implicated.

Food allergic reactions are often considered to be IgE-mediated, where cross-linking of food allergen-specific IgE molecules on the surface of mast cells and basophils occurs following ingestion of the food allergen to which the individual is sensitive, causing immediate and late-phase reactions. The clinical manifestations of such IgE-mediated adverse food reactions may include signs of cutaneous and gastrointestinal (GI) disease. Some patients show signs of vomiting, diarrhoea and abdominal pain. In others, there may be urticaria and angioedema, asthma and rhinitis and, in severe cases, anaphylaxis. The late-phase IgE-mediated reactions may include food-induced eczema and urticaria. Alternatively, other immunopathological mechanisms have been implicated in the causation of food allergy. These non-IgE-mediated mechanisms may involve immune complex or delayed hypersensitivity based reactions (Metcalfe, 1991, Sampson, 1999a).

In human medicine, the method of choice for the demonstration of food allergy is an elimination diet followed by the introduction of selected foods in a sequential fashion; the double-blind placebo-controlled food challenge method is considered the “gold standard” (Sampson, 1999b). A number of in vitro methods have been used to evaluate human patients with suspected food allergy. The detection of serum allergen-specific IgG (notably IgG4) antibodies is assumed to reflect previous exposure to food antigens and is not considered indicative of a specific food-related pathogenesis (Sampson, 1999b). The measurement of food-specific serum IgE can be a useful negative predictive factor—a negative result is considered reliable for ruling out an IgE-mediated reaction to a food. However, the specificity of a positive result is low, although careful measurement of food-specific IgE concentrations has been used to calculate positive and negative predictive values in patients with confirmed food allergy (Sicherer and Sampson, 1999, Yunginger et al., 2000; Sampson, 2001).

In veterinary medicine, food allergy is considered to cause dermatitis more commonly than gastrointestinal disease, and the prevalence of food allergy varies from rare to common according to different authors (Chesney, 2001, Hillier and Griffin, 2001, Scott et al., 2001). Dermatological signs are variable; the most important sign is pruritus, which may start at any age and can be generalised or localised. The pathophysiology of food allergy in animals is not completely understood. Consequently, it has been proposed that the term ‘cutaneous adverse food reactions’ should be used rather than food allergy or food intolerance because the immunopathogenic mechanism is unknown (Hillier and Griffin, 2001).

Attempts to demonstrate an IgE-mediated basis in dogs in naturally occurring cases have previously been unsuccessful. This has shed doubt on the role of IgE and a type 1 hypersensitivity reaction in cutaneous adverse food reactions (Jeffers et al., 1991, Mueller and Tsohalis, 1998). The role of food allergy in causing gastrointestinal disease is even less well characterised. It is presumed that food allergy may arise through abnormal responses by the mucosal immune system to ingested food. The gut is the largest immunological organ in the body and normally generates a local immune response, but systemic tolerance to, an ingested antigen. The current understanding of the normal mucosal immune system is limited and proposed mechanisms of allergy are generally speculative (Hall and Simpson, 2000).

The aims of the present study were to measure the serum concentrations of IgG and IgE antibodies specific for a variety of common food antigens in three groups of dogs. Antibody concentrations were compared between dogs with atopic dermatitis (AD), gastrointestinal diseases and dogs with no clinical disease. Measuring serological responses in large populations of dogs may provide some insight into the type of immune mechanisms that may be present in such conditions.

Section snippets

Materials and methods

The study used serum samples collected from two groups of diseased dogs referred to the University of Bristol Small Animal Hospital, Langford as part of their clinical investigation. Group 1 comprised of dogs with suspected atopic dermatitis (n=91). Group 2 comprised of dogs with suspected gastrointestinal disease (n=72).

Dogs with pruritic skin disease were diagnosed with atopic dermatitis on the basis of a detailed history, the presence of appropriate clinical signs, and consideration of the

Results

There were significant differences between the three groups of dogs in their IgG and IgE responses to the different antigens. There were no detectable differences between the four sub-groups of Group 2 with GI disease in terms of either IgG or IgE response to any of the antigens, and no individual results from these analyses are presented.

Discussion

In human patients with suspected atopic eczema, and/or food allergy, the measurement of serum allergen-specific IgG is not recommended for the investigation of suspected food allergy because both healthy and diseased patients have IgG antibodies to common dietary antigens (Barnes, 1995). Individual IgG antibody responses in dogs may not have a predictive value but examination of a population response (as in this study) may suggest significant trends.

The serum IgG antibody responses to food

Acknowledgements

The skilled technical assistance of Helen Speight and Kate Pinnion.

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