Immunoglobulin E (IgE) is an antibody class involved in the immune response of horses, particularly in allergic reactions and parasitic infections. It binds to allergens and triggers the release of inflammatory mediators from mast cells and basophils. Elevated levels of IgE are often associated with hypersensitivity disorders, such as insect bite hypersensitivity (IBH) in horses. This page assembles peer-reviewed research studies and scholarly articles that investigate the production, regulation, and clinical implications of Immunoglobulin E in equine health, including its role in allergic conditions and potential as a diagnostic marker.
White SJ, Couetil L, Richard EA, Marti E, Wilson PB.Severe asthma (SA) in horses, resembling human asthma, is a prevalent, debilitating allergic respiratory condition marked by elevated allergen-specific immunoglobulin E (IgE) against environmental proteins; however, research exploring the exposome's influence on IgE profiles is currently limited but holds paramount significance for diagnostic and therapeutic developments. Methods: Thirty-five sports horses were analyzed, consisting of environmentally matched samples from France (5 SA; 6 control), the United States (6 SA; 6 control), and Canada (6 SEA; 6 control). Methods: This intentional cros...
Iddagoda J, Gunasekara P, Handunnetti S, Jeewandara C, Karunatilake C, Malavige GN, de Silva R, Dasanayake D.It is clinically important to identify allergens in Artocarpus heterophyllus (jackfruit), Moringa oleifera (moringa), Trianthema portulacastrum (horse purslane) and Syzygium samarangense (rose apple). This study included 7 patients who developed anaphylaxis to jackfruit (1), moringa (2), horse purslane (3) and rose apple (1). We sought to determine allergens in the edible ripening stages of jackfruit (tender, mature, and ripened jackfruit) and seeds, edible parts of moringa (seeds, seedpod, flesh inside seedpod, and leaves), horse purslane leaves and ripened rose apple fruit. The persistence o...
Simonin EM, Wagner B.IgE-binding monocytes are a rare peripheral immune cell type involved in the allergic response through binding of IgE on their surface. IgE-binding monocytes are present in both healthy and allergic individuals. We performed RNA sequencing to ask how the function of IgE-binding monocytes differs in the context of allergy. Using a large animal model of allergy, equine Culicoides hypersensitivity, we compared the transcriptome of IgE-binding monocytes in allergic and non-allergic horses at two seasonal timepoints: (i) when allergic animals were clinical healthy, in the winter "Remission Phase", ...
Simonin EM, Babasyan S, Tarsillo J, Wagner B.IgE+ plasmablasts develop following allergen exposure and B cell activation. They secrete IgE and therefore are directly linked to maintain the mechanisms of IgE-mediated allergies. Here, we show that the presence of IgE+ plasmablasts in peripheral blood not only coincides with clinical allergy, but also predicts the upcoming development of clinical disease. Using an equine model of naturally occurring allergy, we compared the timing of allergen exposure, arrival of IgE+ plasmablasts in peripheral blood, and onset of clinical disease. We found that IgE+ plasmablasts predict the development of ...
Wyler M, Sage SE, Marti E, White S, Gerber V.The diagnostic value of allergen-specific immunoglobulin E (IgE) in horses with asthma is uncertain. A recently developed protein microarray detected abnormally high latex-specific IgE concentrations in the serum of horses with severe asthma. Objective: The main objective was to characterize the IgE profiles of asthmatic horses in Switzerland using a protein microarray platform in serum and bronchoalveolar lavage fluid (BALF). The secondary objective was to determine whether serological and BALF allergen-specific IgE concentrations correlated. Methods: Forty-four asthmatic and 39 control horse...
Stefansdottir SB, Jonsdottir S, Kristjansdottir H, Svansson V, Marti E, Torsteinsdottir S.Insect bite hypersensitivity (IBH) is a seasonal dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides midges characterized by an imbalance of T-cell subsets. Iceland is free of the causative species but the prevalence of IBH in exported Icelandic horses is especially high. We have shown that intralymphatic (i.l.) vaccination with r-Culicoides allergens in Aluminum hydroxide (alum) and monophosphoryl lipid A (MPLA) adjuvants induces a desired Th1/regulatory T-cell response. The aim of this study was to compare i.l. to subcutaneous (s.c.) injection. Twelve healthy Iceland...
Li WJ, Huang ZF, Zhu HQ, Liu Y, Zhang RF, Li GP, Xu M, Hao CL, Zhang SP, Yu YM, Huang DM, Ren HL, Sun X, Sun Y, Ma JH, Li XL, Sun BQ.Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to D...
Cvitas I, Oberhaensli S, Leeb T, Marti E.Equine insect bite hypersensitivity (IBH) is the most common skin disease affecting horses. It is described as an IgE-mediated, Type I hypersensitivity reaction to salivary gland proteins of Culicoides insects. Together with Th2 cells, epithelial barrier cells play an important role in development of Type I hypersensitivities. In order to elucidate the role of equine keratinocytes in development of IBH, we stimulated keratinocytes derived from IBH-affected (IBH-KER) (n = 9) and healthy horses (H-KER) (n = 9) with Culicoides recombinant allergens and extract, allergic cytokine milieu (ACM) and ...
Hopke K, Coleman M, Kneese E, Dominguez B, Diesel A, Patterson A.The existence of antibodies against cross-reactive carbohydrate determinants (CCDs) has been studied extensively in humans, and more recently, in dogs and cats. These antibodies can reduce the specificity of in vitro serum allergen tests. Objective: To investigate the prevalence of anti-CCD immunoglobulin (Ig)E in both allergic and nonallergic horses as well as evaluate its potential impact on serum allergen testing. Methods: Twenty-one allergic and 21 nonallergic horses. Methods: Sera were analysed for anti-CCD IgE utilising a commercial CHO enzyme-linked immunosorbent assay (ELISA)...
Birras J, White SJ, Jonsdottir S, Novotny EN, Ziegler A, Wilson AD, Frey R, Torsteinsdottir S, Alcocer M, Marti E.Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis in horses incited by salivary allergens from Culicoides spp. IBH does not occur in Iceland, as the causative agents are absent, however a high prevalence is seen in horses exported to Culicoides-rich environments. To study the natural course of sensitization to Culicoides allergens and identify the primary sensitizing allergen(s) in horses exported from Iceland utilizing a comprehensive panel of Culicoides recombinant (r-) allergens. IgE microarray profiling to 27 Culicoides r-allergens was conducted on 110 serological s...
Ziegler A, Olzhausen J, Hamza E, Stojiljkovic A, Stoffel MH, Garbani M, Rhyner C, Marti E.Allergen-specific immunotherapy (AIT) constitutes the only curative approach for allergy treatment. There is need for improvement of AIT in veterinary medicine, such as in horses suffering from insect bite hypersensitivity, an IgE-mediated dermatitis to Culicoides. Dendritic cell (DC)-targeting represents an efficient method to increase antigen immunogenicity. It is studied primarily for its use in improvement of cancer therapy and vaccines, but may also be useful for improving AIT efficacy. Immunomodulators, like the Toll-like receptor 4 (TLR-4) agonist monophosphoryl lipid-A (MPLA) has been ...
Musaev A, Sadykova S, Anambayeva A, Saizhanova M, Balkanay G, Kolbaev M.Mare's milk is a highly valuable organic substance that has a great potential to replace cow's milk. Consumption of cow's milk causes digestive disorders in some individuals. Immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is one of the most common food allergies among infants. Therefore, finding a protein substitute with the same nutritional value is a priority. Mare's milk can be a good substitute for cow's milk, especially for those suffering from CMA. Prerequisites for this study were the recent interest in mare's milk, as an ancient relic of the Turkic peoples which contains lots...
Fettelschoss-Gabriel A, Birkmann K, Pantelyushin S, Kündig TM.Equine Culicoides hypersensitivity (CH) is the most common allergic condition in horses affecting the skin. This review focuses on immunopathology and molecular mechanisms of equine CH. The role of eosinophils is emphasized, as well as disease severity and the influence of long-term chronic allergen exposure on T helper (Th) 2 cells. Using current knowledge from human allergic disorders, similar effects are hypothesized in equine patients. Key aspects of CH diagnosis and treatment are discussed, focusing on allergen specific immunotherapy and allergen-independent approaches, such as targeting ...
Jonsdottir S, Torsteinsdottir S, Svansson V, Gudbrandsson J, Stefansdottir SB, Mar Bjornsson J, Runarsdottir A, Marti E.Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses, an IgE-mediated reaction to Culicoides midges. Causative Culicoides spp. are not indigenous in Iceland resulting in high prevalence of IBH in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. The aims were (i) to compare IgE levels in sera of IBH-affected horses born in Iceland (n = 47) with horses of the Icelandic breed (n = 23) and of other breeds (n = 27) born in Culicoides infested area; (ii) to investigate if barley could be a useful production system of allerge...
Raza F, Babasyan S, Larson EM, Freer HS, Schnabel CL, Wagner B.Interleukin-4 (IL-4) is a key cytokine secreted by type 2 T helper (Th2) cells that orchestrates immune responses during allergic reactions. Human and mouse studies additionally suggest that basophils have a unique role in the regulation of allergic diseases by providing initial IL-4 to drive T cell development towards the Th2 phenotype. Equine Culicoides hypersensitivity (CH) is a seasonal immunoglobulin E (IgE)-mediated allergic dermatitis in horses in response to salivary allergens from Culicoides (Cul) midges. Here, we analyzed IL-4 production in peripheral blood mononuclear cells (PBMC) o...
Larson EM, Wagner B.Horses have many naturally occurring diseases that mimic similar conditions in humans. The ability to conduct environmentally controlled experiments and induced disease studies in a genetically diverse host makes the horse a valuable intermediate model between mouse studies and human clinical trials. This review highlights important similarities in the immune landscape between horses and humans using current research on two equine diseases as examples. First, equine herpesvirus type 1 (EHV-1) infection initiates a series of innate inflammatory signals at its mucosal entry site in the upper res...
Enck KM, Lee KW, McKinney BH, Blankenship KD, Montesano C.It has been demonstrated that immunoglobulin (Ig)E specific for cross-reactive carbohydrate determinants (CCD) is present in the serum of sensitized humans, dogs and cats, and that these CCD-specific antibodies might confound serological testing. Objective: The objective was to determine whether or not CCD-reactive antibodies occur in horses and to investigate the prevalence of CCD-reactive IgE antibodies in equine sera using a monoclonal cocktail-based enzyme-linked immunosorbent assay designed to detect allergen-specific IgE in horses, and to evaluate a means for successful inhibition of the...
Larson EM, Babasyan S, Wagner B.IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14/MHC class II/CD16 monocytes, including a subpopulation of IgE-binding mon...
Klier J, Lindner D, Reese S, Mueller RS, Gehlen H.Potential triggers for equine asthma are allergens from hay and straw dusts, mold spores and storage mites. The contribution of these environmental trigger factors to equine asthma is still largely uncertain. The aim of this study was to compare results of four allergy tests from healthy and asthma-affected horses, and to evaluate the clinical relevance of allergens tested positive via specific inhalation provocation test. Fifteen horses were classified using a clinical scoring system as asthmatic (n = 9) or control (n = 6). Four different allergy tests (functional in vitro test, intraderm...
Gislason D, Asmundsson T, Gislason T.Diseases connected with work in hay have been known in Iceland for a long time. In 1981 scientific studies of these diseases were started in Iceland at the request of the Farmers Union. The results of these studies are summarized in this article. In studies of hay a great amount of storage mites, moulds and thermophilic actinomycetes (microlyspora faeni) were found in addition to allergens from mice and pollen. Symptoms caused by hay dust were mainly from nose and eyes in people with positive skin tests, but cough, dyspnea and fever were equally common in those with negative skin tests. The mo...
Trenholme HN, Sakai DM, Berghaus LJ, Hanafi AL, Knych HK, Ryan CA, McHale B, Banovic F, Quandt JE, Barletta M, Reed RA. To evaluate changes in immunological parameters following subcutaneous (SC) and intramuscular (IM) administration of meperidine in horses through quantitative analysis of plasma tryptase, histamine, and IgE levels. Six adult horses were enrolled in a prospective randomized crossover design. Horses were administered one treatment per day, with a seven day washout period: (a) meperidine 1 mg/kg IM, saline 6 mL SC; (b) saline 6 mL IM, meperidine 1 mg/kg SC; (c) saline 6 mL SC, saline 6 mL IM. Blood samples were obtained for plasmatic histamine (baseline, 5, 10, 15, 30, and 60 min) via LC-MS/MS ...
Novotny EN, White SJ, Wilson AD, Stefánsdóttir SB, Tijhaar E, Jonsdóttir S, Frey R, Reiche D, Rose H, Rhyner C, Schüpbach-Regula G....Allergy to bites of blood-sucking insects, including biting midges, can affect both human and veterinary patients. Horses are often suffering from an IgE-mediated allergic dermatitis caused by bites of midges (Culicoides spp). With the aim to improve allergen immunotherapy (AIT), numerous Culicoides allergens have been produced as recombinant (r-) proteins. This study aimed to test a comprehensive panel of differently expressed Culicoides r-allergens on a cohort of IBH-affected and control horses using an allergen microarray. IgE levels to 27 Culicoides r-allergens, including 8 previously unpu...
Raza F, Ivanek R, Freer H, Reiche D, Rose H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Wagner B.Culicoides hypersensitivity (CH) is induced in horses by salivary allergens of Culicoides midges. In Iceland, the causal Culicoides species for CH are not present. Previous epidemiological data indicated that Icelandic horses are more susceptible to CH when they are exported from Iceland and first exposed to Culicoides at adult age. Horses born in countries where Culicoides is endemic, develop the disease less frequently. Here, we established a longitudinal allergy model to identify predictive and diagnostic serological biomarkers of CH. Results: Sixteen adult Icelandic horses from Iceland wer...
van Damme CMM, van den Broek J, Sloet van Oldruitenborgh-Oosterbaan MM.In equine atopic patients intradermal testing (IDT) and immunoglobulin (Ig)E serology are used frequently. There is little evidence regarding the reproducibility of the IDT and IgE serology in horses. Objective: To compare the results of a simultaneously performed IDT on the left and right side of the neck in atopic horses, and to compare these results with allergen-specific IgE serology. Methods: Ten equine patients from a university hospital population with chronic urticaria and/or pruritus. Methods: The IDT was performed using 16 allergens and the results were evaluated after 30 min, 1, 4 ...
Larson EM, Babasyan S, Wagner B.Human IgE-binding monocytes are identified as allergic disease mediators, but it is unknown whether IgE-binding monocytes promote or prevent an allergic response. We identified IgE-binding monocytes in equine peripheral blood as IgE+/MHCIIhigh/CD14low cells that bind IgE through an FcεRI αɣ variant. IgE-binding monocytes were analyzed monthly in Culicoides hypersensitive horses and nonallergic horses living together with natural exposure to Culicoides midges. The phenotype and frequency of IgE-binding monocytes remained consistent in all horses regardless of Culicoides exposure. All horses ...
Cvitas I, Oberhänsli S, Leeb T, Dettwiler M, Müller E, Bruggman R, Marti EI.Insect bite hypersensitivity (IBH) is a Th-2, IgE-mediated dermatitis of horses caused by bites of insects of the genus Culicoides that has common features with human atopic dermatitis. Together with Th-2 cells, the epithelial barrier plays an important role in development of type I hypersensitivities. In order to elucidate the role of the epithelial barrier and of the skin immune response in IBH we studied the transcriptome of lesional whole skin of IBH-horses (IBH-LE; n = 9) in comparison to non-lesional skin (IBH-NL; n = 8) as well as to skin of healthy control horses (H; n = 9). To study t...
Wilkołek P, Szczepanik M, Rodzik B, Sitkowski W, Pluta M, Taszkun I, Gołyński M.Intradermal tests (IDTs) and measurement of specific immunoglobulin E class (sIgE) levels in sera are the most common and reliable methods used in allergological clinical practice. The purpose of this study was to explore the sensitization of pollen allergy in atopic horses with pollinosis and to assess the diagnostic value of the multiple allergen simultaneous tests (MASTs) compared with that of the IDT. Twenty-one Malopolski horses with typical skin hypersensitivity symptoms during pollen seasons were enrolled. Intradermal tests were performed, and allergen-specific IgE concentrations in ser...
Fotschki J, Wróblewska B, Fotschki B, Kalicki B, Rigby N, Mackie A.Horse milk is a valuable raw material and a very attractive alternative for scientific research to address the issue of cow milk (CM) allergy due to its protein profile. A decrease in immunoreactive properties can be achieved by thermal, enzymatic, and hydrolytic processing. Therefore, the aim of this study was to explore the possibility of reducing the immunoreactivity of horse milk proteins by microbial transglutaminase (TG) polymerization. To determine how TG linking alters immunoreactivity under simulated digestion of the examined milk, analyses were performed before, during, and after dig...
Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C.Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin...
Dürrwald R, Kolodziejek J, Weissenböck H, Nowotny N.Borna disease (BD) is a sporadic neurologic disease of horses and sheep caused by mammalian Borna disease virus (BDV). Its unique epidemiological features include: limited occurrence in certain endemic regions of central Europe, yearly varying disease peaks, and a seasonal pattern with higher disease frequencies in spring and a disease nadir in autumn. It is most probably not directly transmitted between horses and sheep. All these features led to the assumption that an indigenous virus reservoir of BDV other than horses and sheep may exist. The search for such a reservoir had been unsuccessfu...
Finkelstein RA.An antiserum specific for Vibrio cholerae exo-enterotoxin was produced by immunization of a horse with purified choleragenoid, a natural cholera toxoid. The serum has a high titer against the toxin antigen in passive hemagglutination tests and a respectable antipermeability factor activity. It also passively protected against choleragen-induced mouse foot edema. The serum was found to be useful for assaying toxin antigen in crude and refined products by in vitro tests such as radial immunodiffusion, Lf, and quantitative precipitin titrations. Based upon experimental observations, the serum was...
Mueller RS, Janda J, Jensen-Jarolim E, Rhyner C, Marti E.Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in...
Schmallenbach KH, Rahman I, Sasse HH, Dixon PM, Halliwell RE, McGorum BC, Crameri R, Miller HR.Inhalant exposure to Aspergillus fumigatus (Asp. f.) antigens induces marked inflammatory and immunological alterations in the lungs of horses affected with chronic obstructive pulmonary disease (COPD). In this study we investigated the role of specific allergen(s) present in Asp. f. on systemic and pulmonary IgE and IgG responses in control and COPD-affected horses, using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting techniques. Compared with controls, horses affected with COPD had significantly higher levels of BALF IgE and IgG to somatic Asp. f. antigens as well as to the ...
Gregoire C, Rosinski-Chupin I, Rabillon J, Alzari PM, David B, Dandeu JP.The gene encoding the major horse allergen, designated Equus caballus allergen 1 (Equ c1), was cloned from total cDNA of sublingual salivary glands by reverse transcription-polymerase chain reaction using synthetic degenerate oligonucleotides deduced from N-terminal and internal peptide sequences of the glycosylated hair dandruff protein. A recombinant form of the protein, with a polyhistidine tail, was expressed in Escherichia coli and purified by immobilized metal affinity chromatography. The recombinant protein is able to induce a passive cutaneous anaphylaxis reaction in rat, and it behave...
Halliwell RE, McGorum BC, Irving P, Dixon PM.An enzyme-linked immunosorbent assay (ELISA) was used to quantify isotype-specific antibody to Micropolyspora faeni and to Aspergillus fumigatus in the sera and bronchoalveolar lavage fluid (BALF) of normal horses, horses with chronic obstructive pulmonary disease (COPD) and horses with other chronic respiratory diseases. Elevated antibody levels were not detected in the sera of affected horses. However, both IgE and IgA antibody to both allergens was significantly elevated in BALF in COPD affected horses sampled both when symptomatic and asymptomatic. Elevated levels were also found in animal...
Künzle F, Gerber V, Van Der Haegen A, Wampfler B, Straub R, Marti E.Recurrent airway obstruction (RAO) is a common condition in stabled horses characterized by small airway inflammation, airway neutrophilia and obstruction following exposure of susceptible horses to mouldy hay and straw and is thus regarded as a hypersensitivity reaction to mould spores. However, the role of immunoglobulin E antibodies (IgE) in the pathogenesis of RAO is unclear. We hypothesized that the number of cells with receptor-bound IgE in bronchoalveolar lavage fluid (BALF) and IgE levels in serum would be higher in RAO-affected than in healthy horses living in the same environment. Th...
Perkins GA, Wagner B.The development of equine immunity from the fetus to adulthood is complex. The foal's immune response and the immune mechanisms that they are equipped with, along with changes over the first months of life until the immune system becomes adult-like, are only partially understood. While several innate immune responses seem to be fully functional from birth, the onset of adaptive immune response is delayed. For some adaptive immune parameters, such as immunoglobin (Ig)G1, IgG3, IgG5 and IgA antibodies, the immune response starts before or at birth and matures within 3 months of life. Other antib...
Eder C, Crameri R, Mayer C, Eicher R, Straub R, Gerber H, Lazary S, Marti E.Immunoglobulin E antibody (IgE) levels against four recombinant (r) mould allergens (r-Aspergillus fumigatus [rAsp f] 7, 8 and 9; r-Alternaria alternata 1 [rAlta1]) and crude mould (Aspergillus fumigatus, Alternaria alternata, Penicillium notatum) and storage mite extracts were determined by ELISA in sera from 24 pulmonary sound control horses and 26 horses suffering from chronic bronchitis/bronchiolitis (CB), also called chronic obstructive pulmonary disease (COPD). Serum IgG and IgA titres were also determined against Aspergillus fumigatus extract and rAsp f 8.IgE against the crude extracts ...
Tahon L, Baselgia S, Gerber V, Doherr MG, Straub R, Robinson NE, Marti E.Recurrent airway obstruction (RAO) is a common condition in stabled horses characterised by small airway inflammation, airway neutrophilia and obstruction following exposure of susceptible horses to mouldy hay and straw and is thus regarded as a hypersensitivity reaction to mould spores. However, the role of IgE-mediated reactions in RAO remains unclear. The aim of the study was to investigate with a serological IgE ELISA test (Allercept), an in vitro sulfidoleukotriene (sLT) release assay (CAST) and with intradermal testing (IDT) whether serum IgE and IgE-mediated reactions against various mo...
Schaffartzik A, Marti E, Torsteinsdottir S, Mellor PS, Crameri R, Rhyner C.Salivary gland proteins of Culicoides spp. have been suggested to be among the main allergens inducing IgE-mediated insect bite hypersensitivity (IBH), an allergic dermatitis of the horse. The aim of our study was to identify, produce and characterize IgE-binding salivary gland proteins of Culicoides nubeculosus relevant for IBH by phage surface display technology. A cDNA library constructed with mRNA derived from C. nubeculosus salivary glands was displayed on the surface of filamentous phage M13 and enriched for clones binding serum IgE of IBH-affected horses. Ten cDNA inserts encoding putat...
Wagner B, Hillegas JM, Babasyan S.CD23, also called FcεRII, is the low-affinity receptor for IgE and has first been described as a major receptor regulating IgE responses. In addition, CD23 also binds to CD21, integrins and MHC class II molecules and thus has a much wider functional role in immune regulation ranging from involvement in antigen-presentation to multiple cytokine-like functions of soluble CD23. The role of CD23 during immune responses of the horse is less well understood. Here, we expressed equine CD23 in mammalian cells using a novel IL-4 expression system. Expression resulted in high yield of recombinant IL-4/...
Wagner B, Perkins G, Babasyan S, Freer H, Keggan A, Goodman LB, Glaser A, Torsteinsdóttir S, Svansson V, Björnsdóttir S.Neonatal foals respond poorly to conventional vaccines. These vaccines typically target T-helper (Th) cell dependent B-cell activation. However, Th2-cell immunity is impaired in foals during the first three months of life. In contrast, neonatal basophils are potent interleukin-4 (IL-4) producers. The purpose of this study was to develop a novel vaccine triggering the natural capacity of neonatal basophils to secrete IL-4 and to evaluate if vaccination resulted in B-cell activation and antibody production against EHV-1 glycoprotein C (gC). Neonatal vaccination was performed by oral biotinylated...
Mendoza L, Mandy W, Glass R.The immunotherapeutic properties of a new Pythium insidiosum-vaccine formulation (PIV), was evaluated in 18 horses and 6 dogs with proven pythiosis from different enzootic areas in the United States. All injected horses but one responded with a weak (=29 mm, n=3), a mild (30-90 mm, n=7) or a strong (=100 mm, n=7) inflammatory reactions at the site of injection. Three equines with weak or negative reactions at the injection site were not cured. Seven equines with strong reactions at their injection sites, however, were cured. Six of the eight horses with mild reactions were also cured. The rema...
Wilson AD, Harwood LJ, Björnsdottir S, Marti E, Day MJ.We postulated that all horses exposed to the bites of Culcoides (midges) would have an antibody response to the antigen secreted in Culcoides saliva, but that IgE antibody would be restricted to allergic individuals. Using immunohistology on sections of fixed Culicoides, we have demonstrated the presence of antibodies in horse serum which recognise Culicoides salivary glands. Antibodies were detected in the serum of horses with insect dermal hypersensitivity and in the serum of normal horses exposed to Culicoides bites. In contrast, no antibodies were detected in serum from native Icelandic po...
van der Meide NM, Roders N, Sloet van Oldruitenborgh-Oosterbaan MM, Schaap PJ, van Oers MM, Leibold W, Savelkoul HF, Tijhaar E.Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity reaction induced by allergens from biting midges of the Culicoides spp. The aim of the present study was to identify, clone and express recombinant allergens from C. obsoletus, the main species found feeding on horses in the Netherlands, by sequence homology searches on the C. obsoletus specific RNA database, with previously described allergens from C. nubeculosus and C. sonorensis. BLAST searches with these described allergens resulted in similarity hits with 7 genes coding for C. obsoletus allergens. These allerg...
D'Auria E, Agostoni C, Giovannini M, Riva E, Zetterström R, Fortin R, Greppi GF, Bonizzi L, Roncada P.As milk represents the main source of nutrition for infants, the question of an effective human milk substitute becomes mandatory when a formula-fed baby is allergic to cows' milk proteins. In this case, formulas containing extensively hydrolysed milk proteins should be preferred, but even such a formula may cause allergic reactions in highly sensitive patients. If there is evidence of cows' milk allergy with IgE-associated symptoms, after 6 mo of age, a soy bean formula may be recommended only when tolerance to soy protein has been established by clinical challenge. In infants with allergic r...
Goubran Botros H, Poncet P, Rabillon J, Fontaine T, Laval JM, David B.A new allergen from horse dander, Equ c 5 has been purified. Its biochemical and biophysical properties have been characterized and compared with those of Equ c 1, Equ c 2 and Equ c 4. Their molecular masses, determined by mass spectrometry, were 22 kDa for Equ c 1, 16 kDa for Equ c 2, 18.7 kDa for Equ c 4 and 16.7 kDa for Equ c 5. Their pI values were between 3.8 and 5.25. Equ c 2 and Equ c 5 are not glycosylated, while Equ c 4 contains a tri-antennary tri-sialylated N-linked glycan. Linkages of terminal N-acetylneuraminic acid to galactose were: alpha-(2-->6) in Equ c 4, and both alpha-(2...
Cabañas R, López-Serrano MC, Carreira J, Ventas P, Polo F, Caballero MT, Contreras J, Barranco P, Moreno-Ancillo A.Different allergenic proteins have been involved in cross-reactivity among animals. Albumins seem to be cross-sensitizing allergenic components. The aim of this study was to assess the importance of albumin as a cross-reactive allergen in patients sensitized to cat, dog and horse. One hundred and seventeen patients sensitized to cat were tested for IgE reactivity using skin prick tests and RAST assays with cat, dog and horse hair/dander extracts and their purified albumin extracts. RAST-inhibition studies were carried out to assess cross-reactivity among cat, dog and horse and among their puri...
Schaffartzik A, Marti E, Crameri R, Rhyner C.Insect bite hypersensitivity (IBH) is an IgE-mediated seasonal dermatitis of the horses associated with bites of Simulium (black fly) and Culicoides (midge) species. Although cross-reactivity between Simulium and Culicoides salivary gland extracts has been demonstrated, the molecular nature of the allergens responsible for the observed cross-reactivity remains to be elucidated. In this report we demonstrate for the first time in veterinary medicine that a homologous allergen, present in the salivary glands of both insects, shows extended IgE cross-reactivity in vitro and in vivo. The cDNA sequ...
Wilson AD, Heesom KJ, Mawby WJ, Mellor PS, Russell CL.IgE-mediated type 1 hypersensitivity reactions to the bites of insects are a common cause of skin disease in horses. Insect bite hypersensitivity (IBH) is most frequently associated with bites of Culicoides spp. and occurs in all parts of the world where horses and Culicoides coexist. The main allergens that cause IBH are probably some of the abundant proteins in the saliva of Culicoides associated with blood feeding. Western blots of Culicoides proteins separated by 1D gel-electrophoresis detected strong IgE responses in all horses with IBH to antigens in protein extracts from wild caught Cul...
Wagner B.Since the initial characterization of IgE by Ishizaka et al. (1966), IgE was described in several mammalian species. In horses, a single gene encoding the IgE heavy chain constant region (IGHE gene) exists per haploid genome and several allelic variants of the equine IGHE gene were found. IgE occurs in its soluble form in equine serum and physiological concentrations of total IgE are around 1000-fold higher in normal horse than in normal human serum. Maternal IgE is enriched in the colostrum and transferred to the neonatal foal after birth. Foals do not produce detectable concentrations of end...
Sheats MK, Davis KU, Poole JA.Farmers are routinely exposed to organic dusts and aeroallergens that can have adverse respiratory health effects including asthma. Horses are farm-reared large animals with similar exposures and can develop equine asthma syndrome (EAS). This review aims to compare the etiology, pathophysiology, and immunology of asthma in horses compared to farmers and highlights the horse as a potential translational animal model for organic dust-induced asthma in humans. Severe EAS shares many clinical and pathological features with various phenotypes of human asthma including allergic, non-allergic, late o...
Derksen FJ, Scott JS, Miller DC, Slocombe RF, Robinson NE.We performed bronchoalveolar lavage (BAL) in 2 groups of ponies. Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction and airway hyperreactivity when ponies are housed in a barn and fed hay; control ponies had no history of airway obstruction. Ponies were paired (principal and control), and BAL was performed after 2 months of being pastured when principal ponies were in clinical remission (Period A), after barn housing when principal ponies had acute airway obstruction (Period B), and after a 1- and a 2-wk recovery phase of pasture grazing (Periods ...
Peeters LM, Janssens S, Goddeeris BM, De Keyser K, Wilson AD, Kaufmann C, Schaffartzik A, Marti E, Buys N.Insect bite hypersensitivity (IBH) in horses represents an immunoglobulin E (IgE)-mediated hypersensitivity to salivary antigens from biting midges (Culicoides spp.). The aim of this study was to evaluate and compare the performances of IgE ELISAs using recombinant Culicoides spp. Obsoletus group salivary gland antigens or crude whole body extracts ('ObsWBE'), C. nubeculosus recombinant proteins (Culn1, 3, 4, 5, 7, 8 and 10) and Obsoletus group recombinant proteins (Culo1 and 2). IgE levels were measured in plasma of 343 Warmblood horses classified as IBH-affected (n=167) and IBH-unaffected (n...
Gershwin LJ, Netherwood KA, Norris MS, Behrens NE, Shao MX.Vaccination of horses is performed annually or semi-annually with multiple viral antigens, either in a combination vaccine or as separate injections. While this practice undoubtedly prevents infection from such diseases as rabies, equine influenza, West Nile virus, and equine herpes virus, the procedure is not without repercussions. Hypersensitivity reactions, including fatal anaphylactic shock, after vaccination, although uncommon, have increased in incidence in recent years. Studies reported herein document the development of IgE antibodies against non-target antigen components of equine vir...
Baker KP, Quinn PJ.Sweet itch is an intensely pruritic dermatitis of horses recurring annually in Ireland from April to November. The tissue changes of sweet itch have similarities to immediate-type hypersensitivity reactions which occur in skin sensitised to the saliva of bloodsucking insects. There was subepidermal oedema, and marked eosinophilia; the blood vessels were tortuous and enlarged. Microfilaria were not found in serial sections of lesions of 5 affected horses. The histopathology of the immediate dermal remal reaction to the intradermal injection of Culicoides extract shows dermal vasodilation and eo...
Hansen S, Otten ND, Birch K, Skovgaard K, Hopster-Iversen C, Fjeldborg J.The pathophysiology of equine asthma (EA) is still not fully described, but the involvement of an allergic reaction is strongly suspected. This theory has led to the use of allergen-specific immunoglobulin (Ig)E tests to support a diagnosis of asthma. The objective of this descriptive study was to evaluate the correlation between four subgroups of EA (mastocytic mild equine asthma [MEA], neutrophilic MEA, mixed MEA, and severe equine asthma [SEA]), allergen specific IgE (measured in both serum and BALF) and mRNA expression of selected genes in bronchoalveolar lavage fluid (BALF). Serum and BAL...