Component-resolved microarray analysis of IgE sensitization profiles to Culicoides recombinant allergens in horses with insect bite hypersensitivity.
Abstract: 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 IgE levels to 27 Culicoides r-allergens, including 8 previously unpublished allergens, of which 11 were expressed in more than one expression system, were determined in sera from 347 horses. ROC analyses were carried out, cut-offs selected using a specificity of 95% and seropositivity rates compared between horses affected with insect bite hypersensitivity (IBH) and control horses. The combination of r-allergens giving the best performing test was determined using logistic regression analysis. Seropositivity was significantly higher in IBH horses compared with controls for 25 r-allergens. Nine Culicoides r-allergens were major allergens for IBH with seven of them binding IgE in sera from > 70% of the IBH-affected horses. Combination of these top seven r-allergens could diagnose > 90% of IBH-affected horses with a specificity of > 95%. Correlation between differently expressed r-allergens was usually high (mean = 0.69, range: 0.28-0.91). This microarray will be a powerful tool for the development of component-resolved, patient-tailored AIT for IBH and could be useful for the study of allergy to biting midges in humans and other species.
© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Publication Date: 2020-09-03 PubMed ID: 32780483PubMed Central: PMC8246938DOI: 10.1111/all.14556Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the allergy in horses caused by bites of blood-sucking insects, specifically midges (Culicoides spp), and tests a range of allergens produced as recombinant proteins to improve immunotherapy. The researchers have developed a microarray tool that can diagnose the allergy and may improve patient-customized treatments for horses.
Research Objectives
- The aim of the study was to investigate the allergic reactions in horses caused by bites from the Culicoides species (midges) with a focus on the role of the immune system protein, IgE.
- By producing numerous Culicoides allergens as recombinant proteins, the researchers also sought to improve allergen immunotherapy (AIT) mechanisms.
Methodology
- A comprehensive panel of differently expressed Culicoides r-allergens were tested on a cohort of horses affected by insect bite hypersensitivity (IBH) and control horses using an allergen microarray.
- IgE levels related to 27 Culicoides r-allergens were measured in sera samples from 347 horses.
- Receiver operating characteristic (ROC) analyses were carried out, and cut-offs were selected using a specificity of 95%.
- The combination of r-allergens leading to the best performing test was determined via a logistic regression analysis.
Key Findings
- The analysis showed that seropositivity was higher in horses suffering from IBH compared to controls for 25 r-allergens.
- Nine Culicoides r-allergens were found to be major allergens for the condition, with seven of them binding the IgE in sera from more than 70% of the IBH-affected horses.
- A combination of these top seven r-allergens could diagnose more than 90% of IBH-affected horses with a specificity of more than 95%, making this a potentially powerful tool in the diagnosis and management of the condition.
Implications for Immunotherapy
- The researchers believe that their allergen microarray could pave the way for component-resolved, patient-tailored AIT for IBH.
- Not only could this allergen microarray serve to improve treatments in horses, but it could also potentially be used to study allergy to biting midges in humans and other species.
Cite This Article
APA
Novotny EN, White SJ, Wilson AD, Stefánsdóttir SB, Tijhaar E, Jonsdóttir S, Frey R, Reiche D, Rose H, Rhyner C, Schüpbach-Regula G, Torsteinsdóttir S, Alcocer M, Marti E.
(2020).
Component-resolved microarray analysis of IgE sensitization profiles to Culicoides recombinant allergens in horses with insect bite hypersensitivity.
Allergy, 76(4), 1147-1157.
https://doi.org/10.1111/all.14556 Publication
Researcher Affiliations
- Department of Clinical Research and VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- School of Animal, Rural and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, Southwell, UK.
- School of Biosciences, University of Nottingham, Loughborough, UK.
- Division of Veterinary Pathology, Infection and Immunity, University of Bristol, Langford, UK.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Reykjavik, Iceland.
- Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
- Department of Clinical Research and VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- AniCura Norsholms Djursjukhus, Norsholm, Sweden.
- Boehringer Ingelheim Vetmedica GmbH, Rohrdorf, Germany.
- Boehringer Ingelheim Vetmedica GmbH, Rohrdorf, Germany.
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
- Department of Clinical Research and VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Institute for Experimental Pathology, Biomedical Center, University of Iceland, Reykjavik, Iceland.
- School of Biosciences, University of Nottingham, Loughborough, UK.
- Department of Clinical Research and VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
MeSH Terms
- Allergens
- Animals
- Ceratopogonidae
- Horse Diseases
- Horses
- Humans
- Hypersensitivity / veterinary
- Immunoglobulin E
- Insect Bites and Stings / veterinary
- Microarray Analysis
Conflict of Interest Statement
All authors have nothing to disclose.
References
This article includes 54 references
Citations
This article has been cited 11 times.- Pessoa VC, Branco-Ferreira M, Jónsdóttir S, Marti E, Tilley P. Comparison of Skin Prick Tests (SPT), Intradermal Tests (IDT) and In Vitro Tests in the Characterization of Insect Bite Hypersensitivity (IBH) in a Population of Lusitano Horses: Contribution for Future Implementation of SPT in IBH Diagnosis. Animals (Basel) 2023 Aug 28;13(17).
- Cox A, Stewart AJ. Insect Bite Hypersensitivity in Horses: Causes, Diagnosis, Scoring and New Therapies. Animals (Basel) 2023 Aug 4;13(15).
- Söderroos D, Ignell R, Haubro Andersen P, Bergvall K, Riihimäki M. The Effect of Insect Bite Hypersensitivity on Movement Activity and Behaviour of the Horse. Animals (Basel) 2023 Apr 8;13(8).
- Wyler M, Sage SE, Marti E, White S, Gerber V. Protein microarray allergen profiling in bronchoalveolar lavage fluid and serum of horses with asthma. J Vet Intern Med 2023 Jan;37(1):328-337.
- Cvitas I, Oberhaensli S, Leeb T, Marti E. Equine keratinocytes in the pathogenesis of insect bite hypersensitivity: Just another brick in the wall?. PLoS One 2022;17(8):e0266263.
- Birras J, White SJ, Jonsdottir S, Novotny EN, Ziegler A, Wilson AD, Frey R, Torsteinsdottir S, Alcocer M, Marti E. First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens. PLoS One 2021;16(11):e0257819.
- Simonin EM, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Freer H, Tarsillo J, Wagner B. Early allergen introduction overrides allergy predisposition in offspring of horses with Culicoides hypersensitivity. Front Immunol 2025;16:1654693.
- Jonsdottir S, Stefansdottir SB, Mirkovitch J, Ziegler A, Torsteinsdottir S, Marti E. Culicoides allergens expressed in insect cells induce sulphidoleukotriene release from peripheral blood leukocytes of horses affected with insect bite hypersensitivity. Front Immunol 2025;16:1597233.
- Graner A, Mueller RS, Geisler J, Bogenstätter D, White SJ, Jonsdottir S, Marti E. Allergen immunotherapy using recombinant Culicoides allergens improves clinical signs of equine insect bite hypersensitivity. Front Allergy 2024;5:1467245.
- Schnabel CL, Jentsch MC, Lübke S, Kaiser-Thom S, Gerber V, Vrtala S, Huang HJ, Rhyner C, Wagner B, Hoffmann R, Volke D. Immunoproteomics reveal increased serum IgG3/5 binding to Dermatophagoides and yeast protein antigens in severe equine asthma in a preliminary study. Front Immunol 2023;14:1293684.
- White SJ, Couetil L, Richard EA, Marti E, Wilson PB. Microarray molecular mapping of horses with severe asthma. J Vet Intern Med 2024 Jan-Feb;38(1):477-484.
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