This article may be helpful for individuals that suspect the food they are feeding is causing problems for their dog. I've removed a section on cats due to character limit, but the link is below to read about them too and for references.
Food Allergy in Dogs and Cats: A Review
April 7, 2006
By Verlinden, A; Hesta, M; Millet, S; Janssens, G P J
Food allergy (FA) is defined as “all immune-mediated reactions following food intake,” in contrast with food intolerance (FI), which is non-immune-mediated. Impairment of the mucosal barrier and loss of oral tolerance are risk factors for the development of FA. Type I, III, and IV hypersensitivity reactions are the most likely immunologic mechanisms. Food allergens are (glyco-)proteins with a molecular weight from 10-70 kDa and are resistant to treatment with heat, acid, and proteases. The exact prevalence of FA in dogs and cats remains unknown. There is no breed, sex or age predilection, although some breeds are commonly affected. Before the onset of clinical signs, the animals have been fed the offending food components for at least two years, although some animals are less than a year old. FA is a non-seasonal disease with skin and/or gastrointestinal disorders. Pruritus is the main complaint and is mostly corticoid-resistant. In 20-30% of the cases, dogs and cats have concurrent allergic diseases (atopy/flea-allergic dermatitis). A reliable diagnosis can only be made with dietary elimination- challenge trials. Provocation testing is necessary for the identification of the causative food component(s). Therapy of FA consists of avoiding the offending food component(s).
Keywords adverse food reactions, clinical signs, diagnosis, hypoallergenic diet, therapy
INTRODUCTION
Food allergy (FA) is recognized as a potential cause of various dermatological and gastrointestinal (GI) signs in the dog and cat. The exact incidence of FA is unknown. However, the term “allergy” is often used indiscriminately. Acquaintance with exact terminology is important when dealing with FA. The aim of this review is to give a survey about the current knowledge of FA based on an extensive literature study. General information concerning the terminology, etiopathogenesis, underlying immunologie mechanisms, and occurrence of FA will be given. Next to it, practical aspects as clinical signs, differential diagnosis, diagnosis, management, and prognosis will be discussed.
TERMINOLOGY
The current terminology of adverse food reactions is advised by the “American Academy of Allergy and Immunology” and the “National Institute of Allergy and Infectious Disease.”2,37 Adverse food reactions (food sensitivity) are divided into two categories: immunological and non-immunological reactions (Table 1). Food allergy (food hypersensitivity) implies all immunological reactions following food intake. Non-immune mediated reactions are indicated as food intolerance (FI). Food idiosyncrasy, food toxicity, and food poisoning, anaphylactic food reaction, pharmacological and metabolic food reactions are all forms of FI. Overlap between the different types is possible, because a clear distinction is difficult.
Food idiosyncrasy describes a quantitatively abnormal response to a food substance or additive which resembles allergy but does not involve immune mechanisms.2 Because previous sensitization is not required, a food idiosyncrasy can occur on the first exposure to the causative substance, which differs from FA. Most of the reactions on food additives are food idiosyncrasies.39
Food intoxication and food poisoning are biological effects caused by an infection or the presence of toxins in foods. These toxins can be inherent to the food or are produced by parasites or micro-organisms.2 Aflatoxicosis (aflatoxins) and botulism (exotoxins of Clostridium botulinwn) are examples of food poisoning by micro- organisms.
Anaphylactoid reactions to food mimic real anaphylaxis, but are not mediated by an immunologie release of chemical mediators. These reactions are also part of FI, food idiosyncrasy, food toxicity, and food poisoning or pharmacological reaction to food.2 Anaphylactoid reactions can occur after ingestion of spoilt tuna which contains large amounts of histamine, resulting from decarboxylation of histidine by bacteria as Proteus and Klebsiella. A non- immunological release of histamine can also be influenced by endorphins in the brain11,86 and might explain why a dog becomes pruritic when he shows signs of euphory.37
Table 1 Classification of adverse reactions to food (adapted from Guilford, 1996a; Roudebush et al., 2000)
A metabolic food reaction is related to the reaction of the metabolism of the host after food intake.2 Reasons for susceptibility to a particular food include disease status, malnutrition, and inborn errors of metabolism.21 Lactose intolerance is a metabolic adverse reaction that can occur in dogs and cats.37,42,64 A form of primary lactose intolerance occurs in puppies.37 When puppies are weaned, lactase activity falls to 10% of the levels found in the young. These pups can only tolerate small amounts of milk, and suffer from diarrhoea after excessive milk intake. In cases of FA, quantities of milk are smaller than those required to induce clinical signs in animals with a dietary intolerance.37 secondary lactose intolerance can affect adult animals with enteritis because of a reduced lactase activity.37
ETIOPATHOGENESIS
The wall of the digestive tract is the largest surface of the body exposed to the environment. The GI tract has to differentiate between nutrients on the one hand and potential harmful substances (bacteria, viruses, parasites) on the other hand, which have to be tolerated and expelled (immunity) respectively.80 The Gut $#@!ociated Lymphoid Tissue (GALT) accomplishes this double function. GALT is composed of four distinct lymphoid compartments: Peyer*s patches (PP) and aggregates of lymphoid follicles throughout the intestinal mucosa, lymphocytes and plasma cells scattered throughout the lamina propria, enterocytes with intraepithelial lymphocytes (IELs), and mesenteric lymph nodes.80 The nature of GALT in the dog and cat is now becoming clearly defined. Canine PP have classical follicular (B lymphocyte) and parafollicular (T lymphocyte) zones and an overlying dome epithelium that constitutively expresses MHC cl$#@! II molecules, which suggests that enterocytes (in addition to M cells) may be important in the transfer of luminal antigen to the underlying lymphoid tissue.23 Plasma cells in the dome of the canine PP predominantly express IgG, but isolated cells produce mostly IgA in the proximal intestine and IgM in the ileum.45*46 The small intestinal lamina propria of the dog contains a mixture of plasma cells (TgA > IgG > IgM), T lymphocytes and MHC II macrophages and dendritic cells, in addition to eosinophils and IgE-bearing mast cells.24*25 Recent studies of the feline small intestinal mucosa have identified several differences to the dog: a much larger population of IELs, a lack of constitutive expression of MHC II by enterocytes, and a higher concentration of lamina propria plasma cells in the ileum compared to the duodenum.72*96
Four mechanisms ensure the conflicting functions of tolerance and exclusion of antigens: (1) the mucosal barrier, (2) regulation of the immune response, (3) elimination and (4) tolerance of antigens reaching the mucosa.31 Impairment of this GI defence predisposes patients to FA.
Mucosal Barrier
Exclusion of substances from the lumen is ensured by components of the mucosal barrier, which is composed of different interrelated immunologie and non-immunologic components (Table 2). The rate of intact protein absorption depends on the integrity of the mucosal barrier, to which different factors contribute: morphology and functionality of the enterocytes, presence of IgA, effective digestion, quality and composition of the food and presence of inflammation.30
Table 2 Components of the mucosal barrier (adapted iiom Sampson, 1991)
According to available data in man, the maturation of the enterocyte depends on the age and the stage of development along the crypt-villus axis.85 The uptake of antigen by the enterocytes depends on the content of proteins and phospholipids of the cell membrane. A change in composition and function of the enterocytes occurs at a young age.83 The larger neonatal permeability of enterocytes enhances the absorption of food molecules and colostral antibodies. During the development of the enterocyte along the crypt- villus axis, the composition of the cell membrane also changes: immature crypt cells have twice the endocytotic capacity (i.e. protein absorption) of mature crypt cells.85 Recent research in dogs concerning postnatal development of nutrient transport in the intestine of dogs, revealed a decreased absorption for most nutrients between birth and adulthood.10
IgA is an important immunologie component of the mucosal barrier.83 In the intestinal secretions, IgA is mainly present in the secretory form (slgA): two monomeric IgA molecules are covalently bound by a peptide (J-chain) synthesised by IgA- producing plasma cells. This dimeric form of IgA is transported actively through the epithelia of the gut mucosa and is added to a secretory component of the epithelial cell. Owing to this, slgA is formed, which is resistant to enzymatic degradation. IgA may complex with food antigens thereby preventing their transport through the mucosa. After attachment to the glycocalyx, the antigen-IgA complex is more sensitive to proteolytic digestion than the free antigen in the gut lumen.
An effective digestion of proteins results in free amino acids and small peptides which are poor antigens, whilst incomple\te digestion leads to exposure of larger polypeptides with residual antigenic properties which can still elicit an allergic reaction.80
Malnutrition increases intestinal permeability to macromolecules by changing the morphology and activity of the enterocytes.85 More proteins can p$#@! the mucosal barrier because of incomplete digestion and enhanced possibility of protein absorption.
Diet composition can influence protein absorption in two ways: consuming a protein along with other proteins decreases individual absorption rates of the proteins, whereas protein absorption will increase when ingesting a protein with glucose.85
Regulation of the Immune Response
Penetration of the epithelium by an antigen evokes an immune response. This happens constantly, but the organism differentiates between “good” and “bad” antigens to prevent a continuous immune reaction. M-cells (specialised epithelial cells for antigen presentation in the Peyer*s patches)31 take up small amounts of antigen, and present it to the underlying lymphoid tissue.83 Immune reactions can be prevented by T-cell suppression, which leads to tolerance. In cases of FA however, an antigenspecific immune reaction with formation of IgM, IgG, or IgE occurs.84
Elimination of Antigens
In spite of the defence, the mucosal barrier is not totally impermeable to macromolecules even in normal circumstances. Small but immunologie significant amounts of dietary proteins cross the intact mucosa and reach the systemic immune system. Formed immune complexes are removed by the mononuclear phagocytic system of the liver and the mesenterial lymph nodes.31 The consequences of increased mucosal permeability and increased circulating immune complexes against food components are unpredictable. Contributing factors are species, age of the animal, type and quantity of the antigen absorbed, location of the absorption, pathophysiological state and genetic makeup of the host.85 In some cases, oral tolerance to the absorbed antigen is maintained, whilst in other situations the suppressor response of the GALT is by-passed and local inflammation results. Hypersensitivity rather than tolerance to the absorbed protein develops (see also regulation of the immune response and oral tolerance).
Oral Tolerance
Oral tolerance is the phenomenon whereby prior exposure to an antigen by the enteric route induces a specific immunological unresponsiveness (locally and systemically) on subsequent systemic exposure to the same antigen.16 The suppressor function of the GALT (cellular immunity) is the basis of oral tolerance. In addition to the suppressor response, the gut-$#@!ociated humoral immune system generates IgA, which is secreted on the mucosal surface. Although oral tolerance is essential to life, animals are not born with it. It develops at a young age, but the exact time is unknown. When animals are weaned and start eating new foods, they have to be able of develop oral tolerance. It is estimated that puppies and kittens have this potential from 6 weeks on.89 If new food components are consumed before that age, it is likely that oral tolerance will not develop, which can result in an allergy to that food. Induction of oral tolerance is more effective after repetitive contact with smaller amounts of protein during several weeks.31 Without new exposure to the antigen, oral tolerance will be reduced. A study carried out by Zemann et al. (2003) describes a successful protocol for tolerance induction in atopic dogs. Oral tolerance was induced by means of a 28-day treatment with ovalbumin dissolved in cow*s milk starting at the age of 9 weeks.
IMMUNOLOGIC MECHANISMS
The most common studied and best defined allergic reactions to food in man are IgE-mediated reactions (Type I hypersensitivity) that lead to clinical symptoms of immediate hypersensitivity (within a few minutes to hours after food intake). IgE-activated mast cells can release cytokines that cause a delayed hypersensitivity reaction (within a few hours to days). Type II (cytotoxic reactions), Type III (mediated by immune complexes) and Type IV (cell mediated) hypersensitivity reactions have been implicated in food-allergic disorders in people and other animals, but their involvement in FA in the dog and cat has not been clearly established.80 In dogs and cats, Type I, Type III, and Type IV hypersensitivity are possible immunologie mechanisms.63 Table 3 gives an overview of the different types of hypersensitivity reactions.
Immediate Hypersensitivity
Immediate hypersensitivities to food occur within a few minutes to several hours after ingestion of the offending antigen. These responses are mediated by IgE bound on mast cells.16 In all probability this is also true for cats and dogs.47,48,56,100 Without oral tolerance, an individual develops an IgE response to a certain food antigen instead of an IgA response.16 IgE binds on GI and peripheric mast cells, which leads to sensitization for the causative food antigen. On subsequent contact with the antigen, mast cell degranulation occurs. This releases a range of inflammatory mediators. When the sensitized mast cells are limited to the GI tract, a local and intestinal Type I hypersensitivity reaction causes loss of fluid, plasma proteins, and blood through the capillaries of the gut into the lumen.16 The stimulated secretion of mucus and chloride disturbs motility and disaccharidase activity. These changes lead to clinical symptoms of vomiting, diarrhoea, and weight loss. In some cases, repeated degranulation of mast cells leads eventually to accumulation of eosinophils in the gut wall, resulting in eosinophilic gastroenteritis.61 The increase in absorption of macromolecules following gastrointestinal hypersensitivity can deteriorate the allergic reaction or may even lead to multiple hypersensitivities.16 More general reactions occur when the antigen escapes from the gut and reaches sensitized basophils or IgE-bearing mast cells in the skin. Extra- gastrointestinal effects are also possible after the release of gastrointestinal mast cell mediators in the systemic circulation.83
Table 3 Comparison of different types of hypersensitivity reactions (Roitt, 1991)
Intermediate Hypersensitivity
When judging the reported timing of occurrence of adverse reactions after food challenge, intermediate hypersensitivities to food appear frequently in dogs and cats.51*95,98 They occur several hours after antigen ingestion and are probably the result of a late- phase response to IgE-mediated mast cell degranulation and/or type III hypersensitivity response to immune complexes. Activated mast cells release a great number of cytokines, which attract neutrophils, eosinophils, and in smaller amounts also lymphocytes. These cells also release other mediators, evoking chronic inflammation.83 In man, IgA complexes dominate the lamina propria of normal people. These are non-inflammatory and are quickly eliminated by the liver. In food-allergic people, IgE and IgG complexes are thought to accumulate in the gastrointestinal mucosa.83 This leads to an inflammatory response by the fixation of complement and the attraction of phagocytes. Moreover, IgG and IgE complexes are another stimulus for mast cell degranulation and eosinophil migration and may contribute to the eosinophilic infiltration seen in some cases of FA.16
Delayed Hypersensitivity
In man, delayed type hypersensitivity (DTH) reactions appear several hours to 2-3 days after ingestion of the allergen and are probably mediated by Type III and Type IV reactions.16,83 Non- specific symptoms such as recurrent abdominal pain, fatigue, arthropathies, oral ulcers and GI upsets can be seen. The prevalence of DTH responses to food in the canine and feline population is unknown, but clinical experiences indicate their occurrence.51,95,97
Table 4 Common food allergens in the dog
FOOD ALLERGENS
General Characteristics
Although all food proteins are antigenic (foreign to the body), only a small component of the total protein content of a food is allergenic: the capacity of a protein to induce an allergic reaction is influenced by the immunogenicity and the permeability of the gut for the protein.90 Allergen immunogenicity depends on stimulation of IgE production and histamine release of mast cells after bridging of the allergen between two IgE molecules on the surface of the mast cell membrane.90 This requirement places a minimum size limit on molecules that can stimulate IgE production. The maximum size limit is related to the absorption capacity of the enteric mucosa for the protein. In man, food allergens are almost exclusively glycoproteins with a molecular weight (MW) of 10-70 kDa.90 In dogs and cats no data are available on the exact MWs of food allergens.
Factors that determine which proteins are the most important allergens are incompletely understood. Immunogenicity and stability of the protein play an important role.90 Food allergens maintain their immunogenicity in spite of different treatments: a lot of allergens are partially resistant to influence of heat and acid and can resist the digestion process. However, it seems that allergenicity can be influenced by food processing: protein denaturation can destroy old epitopes (antigenic determinants) or expose new ones, with a decrease or increase of allergenicity respectively.30 The importance of this phenomenon in FA is under debate, but it appears that the allergenicity of most foods is either unchanged or reduced by cooking or partial digestion.4,51 Maillard reactant products are formed when proteins are cooked with carbohydrate. They can increase or decrease the allergenicity of proteins, depending on the food component. This phenomenon may explain the apparent increase in allergenicity of proteins in canned pet foods compared to fresh proteins.30
Table 5 Common food allergens in the cat
Common Food Allergens in Dogs and Cats
There are a lot of potential food allergens an\d because of the multiple ingredient content in commercial pet food, it is difficult to detect the specific causative food allergens. Several publications have been analyzed in which the allergen has been identified by elimination and single ingredient challenge trials yields in dogs.13-19,40,51,52,68,95 and cats28,32,33-60,70,88,95 with FA. The allergens are presented in Tables 4 and 5, for dogs and cats respectively. Veterinarians believe that food additives (dyes and preservatives) are common food allergens.76 However, not one case was found in literature for dogs and only two cases for cats.32*33 Moreover, most reactions on food additives are types of FI.39
Multiple Food Hypersensitivities
According to Walton (1967), multiple hypersensitivities are uncommon in dogs and cats. However, Harvey (1993) and Paterson (1995) showed that 35^8% of the dogs were allergic to more than one food component. According to Jeffers et al. (1996), the average number of allergic reactions per dog is 2.4. A study in cats with chronic gastrointestinal problems,33 revealed 50% of the cats with FA allergic to more than one food component. These findings show the importance of systematic introduction of specific food components to the elimination diet to identify a food allergen. Moreover, testing other ingredients should not be neglected when one causative substance has already been identified (see diagnosis).
Cross-Reactivity
In some groups of food, allergy for one member of the group can result in a variable degree of allergy for the other members of the same group, because of antigenic similarity between food allergens.7 In man, this cross-reactivity is sometimes seen with sea foods, vegetables, and cereals. Cross reactivity in other foods is far less seen, even when the origin is the same species. Research in man has shown that FA usually is specific.7 and that dietary restrictions of entire food families are rarely needed. Also in dogs, cross- reactivity among products of the same animal species or between different vegetable products has not been demonstrated. Jeffers et al. (1996) showed that there was a significant difference between the number of dogs allergic to beef versus milk, and for soy versus wheat. This refutes a possible cross-reactivity between proteins from bovine origin and to soy and wheat. Hence, a dog allergic to cow milk usually can tolerate beef.51,95
Read more at Food Allergy in Dogs and Cats: A Review - Health News - redOrbit
Quote:
Food Allergy in Dogs and Cats: A Review
April 7, 2006
By Verlinden, A; Hesta, M; Millet, S; Janssens, G P J
Food allergy (FA) is defined as “all immune-mediated reactions following food intake,” in contrast with food intolerance (FI), which is non-immune-mediated. Impairment of the mucosal barrier and loss of oral tolerance are risk factors for the development of FA. Type I, III, and IV hypersensitivity reactions are the most likely immunologic mechanisms. Food allergens are (glyco-)proteins with a molecular weight from 10-70 kDa and are resistant to treatment with heat, acid, and proteases. The exact prevalence of FA in dogs and cats remains unknown. There is no breed, sex or age predilection, although some breeds are commonly affected. Before the onset of clinical signs, the animals have been fed the offending food components for at least two years, although some animals are less than a year old. FA is a non-seasonal disease with skin and/or gastrointestinal disorders. Pruritus is the main complaint and is mostly corticoid-resistant. In 20-30% of the cases, dogs and cats have concurrent allergic diseases (atopy/flea-allergic dermatitis). A reliable diagnosis can only be made with dietary elimination- challenge trials. Provocation testing is necessary for the identification of the causative food component(s). Therapy of FA consists of avoiding the offending food component(s).
Keywords adverse food reactions, clinical signs, diagnosis, hypoallergenic diet, therapy
INTRODUCTION
Food allergy (FA) is recognized as a potential cause of various dermatological and gastrointestinal (GI) signs in the dog and cat. The exact incidence of FA is unknown. However, the term “allergy” is often used indiscriminately. Acquaintance with exact terminology is important when dealing with FA. The aim of this review is to give a survey about the current knowledge of FA based on an extensive literature study. General information concerning the terminology, etiopathogenesis, underlying immunologie mechanisms, and occurrence of FA will be given. Next to it, practical aspects as clinical signs, differential diagnosis, diagnosis, management, and prognosis will be discussed.
TERMINOLOGY
The current terminology of adverse food reactions is advised by the “American Academy of Allergy and Immunology” and the “National Institute of Allergy and Infectious Disease.”2,37 Adverse food reactions (food sensitivity) are divided into two categories: immunological and non-immunological reactions (Table 1). Food allergy (food hypersensitivity) implies all immunological reactions following food intake. Non-immune mediated reactions are indicated as food intolerance (FI). Food idiosyncrasy, food toxicity, and food poisoning, anaphylactic food reaction, pharmacological and metabolic food reactions are all forms of FI. Overlap between the different types is possible, because a clear distinction is difficult.
Food idiosyncrasy describes a quantitatively abnormal response to a food substance or additive which resembles allergy but does not involve immune mechanisms.2 Because previous sensitization is not required, a food idiosyncrasy can occur on the first exposure to the causative substance, which differs from FA. Most of the reactions on food additives are food idiosyncrasies.39
Food intoxication and food poisoning are biological effects caused by an infection or the presence of toxins in foods. These toxins can be inherent to the food or are produced by parasites or micro-organisms.2 Aflatoxicosis (aflatoxins) and botulism (exotoxins of Clostridium botulinwn) are examples of food poisoning by micro- organisms.
Anaphylactoid reactions to food mimic real anaphylaxis, but are not mediated by an immunologie release of chemical mediators. These reactions are also part of FI, food idiosyncrasy, food toxicity, and food poisoning or pharmacological reaction to food.2 Anaphylactoid reactions can occur after ingestion of spoilt tuna which contains large amounts of histamine, resulting from decarboxylation of histidine by bacteria as Proteus and Klebsiella. A non- immunological release of histamine can also be influenced by endorphins in the brain11,86 and might explain why a dog becomes pruritic when he shows signs of euphory.37
Table 1 Classification of adverse reactions to food (adapted from Guilford, 1996a; Roudebush et al., 2000)
A metabolic food reaction is related to the reaction of the metabolism of the host after food intake.2 Reasons for susceptibility to a particular food include disease status, malnutrition, and inborn errors of metabolism.21 Lactose intolerance is a metabolic adverse reaction that can occur in dogs and cats.37,42,64 A form of primary lactose intolerance occurs in puppies.37 When puppies are weaned, lactase activity falls to 10% of the levels found in the young. These pups can only tolerate small amounts of milk, and suffer from diarrhoea after excessive milk intake. In cases of FA, quantities of milk are smaller than those required to induce clinical signs in animals with a dietary intolerance.37 secondary lactose intolerance can affect adult animals with enteritis because of a reduced lactase activity.37
ETIOPATHOGENESIS
The wall of the digestive tract is the largest surface of the body exposed to the environment. The GI tract has to differentiate between nutrients on the one hand and potential harmful substances (bacteria, viruses, parasites) on the other hand, which have to be tolerated and expelled (immunity) respectively.80 The Gut $#@!ociated Lymphoid Tissue (GALT) accomplishes this double function. GALT is composed of four distinct lymphoid compartments: Peyer*s patches (PP) and aggregates of lymphoid follicles throughout the intestinal mucosa, lymphocytes and plasma cells scattered throughout the lamina propria, enterocytes with intraepithelial lymphocytes (IELs), and mesenteric lymph nodes.80 The nature of GALT in the dog and cat is now becoming clearly defined. Canine PP have classical follicular (B lymphocyte) and parafollicular (T lymphocyte) zones and an overlying dome epithelium that constitutively expresses MHC cl$#@! II molecules, which suggests that enterocytes (in addition to M cells) may be important in the transfer of luminal antigen to the underlying lymphoid tissue.23 Plasma cells in the dome of the canine PP predominantly express IgG, but isolated cells produce mostly IgA in the proximal intestine and IgM in the ileum.45*46 The small intestinal lamina propria of the dog contains a mixture of plasma cells (TgA > IgG > IgM), T lymphocytes and MHC II macrophages and dendritic cells, in addition to eosinophils and IgE-bearing mast cells.24*25 Recent studies of the feline small intestinal mucosa have identified several differences to the dog: a much larger population of IELs, a lack of constitutive expression of MHC II by enterocytes, and a higher concentration of lamina propria plasma cells in the ileum compared to the duodenum.72*96
Four mechanisms ensure the conflicting functions of tolerance and exclusion of antigens: (1) the mucosal barrier, (2) regulation of the immune response, (3) elimination and (4) tolerance of antigens reaching the mucosa.31 Impairment of this GI defence predisposes patients to FA.
Mucosal Barrier
Exclusion of substances from the lumen is ensured by components of the mucosal barrier, which is composed of different interrelated immunologie and non-immunologic components (Table 2). The rate of intact protein absorption depends on the integrity of the mucosal barrier, to which different factors contribute: morphology and functionality of the enterocytes, presence of IgA, effective digestion, quality and composition of the food and presence of inflammation.30
Table 2 Components of the mucosal barrier (adapted iiom Sampson, 1991)
According to available data in man, the maturation of the enterocyte depends on the age and the stage of development along the crypt-villus axis.85 The uptake of antigen by the enterocytes depends on the content of proteins and phospholipids of the cell membrane. A change in composition and function of the enterocytes occurs at a young age.83 The larger neonatal permeability of enterocytes enhances the absorption of food molecules and colostral antibodies. During the development of the enterocyte along the crypt- villus axis, the composition of the cell membrane also changes: immature crypt cells have twice the endocytotic capacity (i.e. protein absorption) of mature crypt cells.85 Recent research in dogs concerning postnatal development of nutrient transport in the intestine of dogs, revealed a decreased absorption for most nutrients between birth and adulthood.10
IgA is an important immunologie component of the mucosal barrier.83 In the intestinal secretions, IgA is mainly present in the secretory form (slgA): two monomeric IgA molecules are covalently bound by a peptide (J-chain) synthesised by IgA- producing plasma cells. This dimeric form of IgA is transported actively through the epithelia of the gut mucosa and is added to a secretory component of the epithelial cell. Owing to this, slgA is formed, which is resistant to enzymatic degradation. IgA may complex with food antigens thereby preventing their transport through the mucosa. After attachment to the glycocalyx, the antigen-IgA complex is more sensitive to proteolytic digestion than the free antigen in the gut lumen.
An effective digestion of proteins results in free amino acids and small peptides which are poor antigens, whilst incomple\te digestion leads to exposure of larger polypeptides with residual antigenic properties which can still elicit an allergic reaction.80
Malnutrition increases intestinal permeability to macromolecules by changing the morphology and activity of the enterocytes.85 More proteins can p$#@! the mucosal barrier because of incomplete digestion and enhanced possibility of protein absorption.
Diet composition can influence protein absorption in two ways: consuming a protein along with other proteins decreases individual absorption rates of the proteins, whereas protein absorption will increase when ingesting a protein with glucose.85
Regulation of the Immune Response
Penetration of the epithelium by an antigen evokes an immune response. This happens constantly, but the organism differentiates between “good” and “bad” antigens to prevent a continuous immune reaction. M-cells (specialised epithelial cells for antigen presentation in the Peyer*s patches)31 take up small amounts of antigen, and present it to the underlying lymphoid tissue.83 Immune reactions can be prevented by T-cell suppression, which leads to tolerance. In cases of FA however, an antigenspecific immune reaction with formation of IgM, IgG, or IgE occurs.84
Elimination of Antigens
In spite of the defence, the mucosal barrier is not totally impermeable to macromolecules even in normal circumstances. Small but immunologie significant amounts of dietary proteins cross the intact mucosa and reach the systemic immune system. Formed immune complexes are removed by the mononuclear phagocytic system of the liver and the mesenterial lymph nodes.31 The consequences of increased mucosal permeability and increased circulating immune complexes against food components are unpredictable. Contributing factors are species, age of the animal, type and quantity of the antigen absorbed, location of the absorption, pathophysiological state and genetic makeup of the host.85 In some cases, oral tolerance to the absorbed antigen is maintained, whilst in other situations the suppressor response of the GALT is by-passed and local inflammation results. Hypersensitivity rather than tolerance to the absorbed protein develops (see also regulation of the immune response and oral tolerance).
Oral Tolerance
Oral tolerance is the phenomenon whereby prior exposure to an antigen by the enteric route induces a specific immunological unresponsiveness (locally and systemically) on subsequent systemic exposure to the same antigen.16 The suppressor function of the GALT (cellular immunity) is the basis of oral tolerance. In addition to the suppressor response, the gut-$#@!ociated humoral immune system generates IgA, which is secreted on the mucosal surface. Although oral tolerance is essential to life, animals are not born with it. It develops at a young age, but the exact time is unknown. When animals are weaned and start eating new foods, they have to be able of develop oral tolerance. It is estimated that puppies and kittens have this potential from 6 weeks on.89 If new food components are consumed before that age, it is likely that oral tolerance will not develop, which can result in an allergy to that food. Induction of oral tolerance is more effective after repetitive contact with smaller amounts of protein during several weeks.31 Without new exposure to the antigen, oral tolerance will be reduced. A study carried out by Zemann et al. (2003) describes a successful protocol for tolerance induction in atopic dogs. Oral tolerance was induced by means of a 28-day treatment with ovalbumin dissolved in cow*s milk starting at the age of 9 weeks.
IMMUNOLOGIC MECHANISMS
The most common studied and best defined allergic reactions to food in man are IgE-mediated reactions (Type I hypersensitivity) that lead to clinical symptoms of immediate hypersensitivity (within a few minutes to hours after food intake). IgE-activated mast cells can release cytokines that cause a delayed hypersensitivity reaction (within a few hours to days). Type II (cytotoxic reactions), Type III (mediated by immune complexes) and Type IV (cell mediated) hypersensitivity reactions have been implicated in food-allergic disorders in people and other animals, but their involvement in FA in the dog and cat has not been clearly established.80 In dogs and cats, Type I, Type III, and Type IV hypersensitivity are possible immunologie mechanisms.63 Table 3 gives an overview of the different types of hypersensitivity reactions.
Immediate Hypersensitivity
Immediate hypersensitivities to food occur within a few minutes to several hours after ingestion of the offending antigen. These responses are mediated by IgE bound on mast cells.16 In all probability this is also true for cats and dogs.47,48,56,100 Without oral tolerance, an individual develops an IgE response to a certain food antigen instead of an IgA response.16 IgE binds on GI and peripheric mast cells, which leads to sensitization for the causative food antigen. On subsequent contact with the antigen, mast cell degranulation occurs. This releases a range of inflammatory mediators. When the sensitized mast cells are limited to the GI tract, a local and intestinal Type I hypersensitivity reaction causes loss of fluid, plasma proteins, and blood through the capillaries of the gut into the lumen.16 The stimulated secretion of mucus and chloride disturbs motility and disaccharidase activity. These changes lead to clinical symptoms of vomiting, diarrhoea, and weight loss. In some cases, repeated degranulation of mast cells leads eventually to accumulation of eosinophils in the gut wall, resulting in eosinophilic gastroenteritis.61 The increase in absorption of macromolecules following gastrointestinal hypersensitivity can deteriorate the allergic reaction or may even lead to multiple hypersensitivities.16 More general reactions occur when the antigen escapes from the gut and reaches sensitized basophils or IgE-bearing mast cells in the skin. Extra- gastrointestinal effects are also possible after the release of gastrointestinal mast cell mediators in the systemic circulation.83
Table 3 Comparison of different types of hypersensitivity reactions (Roitt, 1991)
Intermediate Hypersensitivity
When judging the reported timing of occurrence of adverse reactions after food challenge, intermediate hypersensitivities to food appear frequently in dogs and cats.51*95,98 They occur several hours after antigen ingestion and are probably the result of a late- phase response to IgE-mediated mast cell degranulation and/or type III hypersensitivity response to immune complexes. Activated mast cells release a great number of cytokines, which attract neutrophils, eosinophils, and in smaller amounts also lymphocytes. These cells also release other mediators, evoking chronic inflammation.83 In man, IgA complexes dominate the lamina propria of normal people. These are non-inflammatory and are quickly eliminated by the liver. In food-allergic people, IgE and IgG complexes are thought to accumulate in the gastrointestinal mucosa.83 This leads to an inflammatory response by the fixation of complement and the attraction of phagocytes. Moreover, IgG and IgE complexes are another stimulus for mast cell degranulation and eosinophil migration and may contribute to the eosinophilic infiltration seen in some cases of FA.16
Delayed Hypersensitivity
In man, delayed type hypersensitivity (DTH) reactions appear several hours to 2-3 days after ingestion of the allergen and are probably mediated by Type III and Type IV reactions.16,83 Non- specific symptoms such as recurrent abdominal pain, fatigue, arthropathies, oral ulcers and GI upsets can be seen. The prevalence of DTH responses to food in the canine and feline population is unknown, but clinical experiences indicate their occurrence.51,95,97
Table 4 Common food allergens in the dog
FOOD ALLERGENS
General Characteristics
Although all food proteins are antigenic (foreign to the body), only a small component of the total protein content of a food is allergenic: the capacity of a protein to induce an allergic reaction is influenced by the immunogenicity and the permeability of the gut for the protein.90 Allergen immunogenicity depends on stimulation of IgE production and histamine release of mast cells after bridging of the allergen between two IgE molecules on the surface of the mast cell membrane.90 This requirement places a minimum size limit on molecules that can stimulate IgE production. The maximum size limit is related to the absorption capacity of the enteric mucosa for the protein. In man, food allergens are almost exclusively glycoproteins with a molecular weight (MW) of 10-70 kDa.90 In dogs and cats no data are available on the exact MWs of food allergens.
Factors that determine which proteins are the most important allergens are incompletely understood. Immunogenicity and stability of the protein play an important role.90 Food allergens maintain their immunogenicity in spite of different treatments: a lot of allergens are partially resistant to influence of heat and acid and can resist the digestion process. However, it seems that allergenicity can be influenced by food processing: protein denaturation can destroy old epitopes (antigenic determinants) or expose new ones, with a decrease or increase of allergenicity respectively.30 The importance of this phenomenon in FA is under debate, but it appears that the allergenicity of most foods is either unchanged or reduced by cooking or partial digestion.4,51 Maillard reactant products are formed when proteins are cooked with carbohydrate. They can increase or decrease the allergenicity of proteins, depending on the food component. This phenomenon may explain the apparent increase in allergenicity of proteins in canned pet foods compared to fresh proteins.30
Table 5 Common food allergens in the cat
Common Food Allergens in Dogs and Cats
There are a lot of potential food allergens an\d because of the multiple ingredient content in commercial pet food, it is difficult to detect the specific causative food allergens. Several publications have been analyzed in which the allergen has been identified by elimination and single ingredient challenge trials yields in dogs.13-19,40,51,52,68,95 and cats28,32,33-60,70,88,95 with FA. The allergens are presented in Tables 4 and 5, for dogs and cats respectively. Veterinarians believe that food additives (dyes and preservatives) are common food allergens.76 However, not one case was found in literature for dogs and only two cases for cats.32*33 Moreover, most reactions on food additives are types of FI.39
Multiple Food Hypersensitivities
According to Walton (1967), multiple hypersensitivities are uncommon in dogs and cats. However, Harvey (1993) and Paterson (1995) showed that 35^8% of the dogs were allergic to more than one food component. According to Jeffers et al. (1996), the average number of allergic reactions per dog is 2.4. A study in cats with chronic gastrointestinal problems,33 revealed 50% of the cats with FA allergic to more than one food component. These findings show the importance of systematic introduction of specific food components to the elimination diet to identify a food allergen. Moreover, testing other ingredients should not be neglected when one causative substance has already been identified (see diagnosis).
Cross-Reactivity
In some groups of food, allergy for one member of the group can result in a variable degree of allergy for the other members of the same group, because of antigenic similarity between food allergens.7 In man, this cross-reactivity is sometimes seen with sea foods, vegetables, and cereals. Cross reactivity in other foods is far less seen, even when the origin is the same species. Research in man has shown that FA usually is specific.7 and that dietary restrictions of entire food families are rarely needed. Also in dogs, cross- reactivity among products of the same animal species or between different vegetable products has not been demonstrated. Jeffers et al. (1996) showed that there was a significant difference between the number of dogs allergic to beef versus milk, and for soy versus wheat. This refutes a possible cross-reactivity between proteins from bovine origin and to soy and wheat. Hence, a dog allergic to cow milk usually can tolerate beef.51,95
Read more at Food Allergy in Dogs and Cats: A Review - Health News - redOrbit
Food Allergy in Dogs and Cats: A Review
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