Testing for insect bite hypersensitivity

I have wrote often on the problems of using blood and skin tests for diagnosing the causes of allergies in horses. The problem is the lack of specificity and sensitivity. Specificity is the ability to rule out those not affected by the condition you are testing for. Sensitivity is the ability to identify those who are affected by the condition. Here is a testing method that seems to identify Culicoides hypersensitivity with greater than 90% sensitivity and 95% specificity.
DrO

Component-resolved microarray analysis of IgE sensitization profiles to Culicoides recombinant allergens in horses with insect bite hypersensitivity
Allergy. 2020 Aug 11.

Authors
Ella N Novotny 1 , Samuel White 2 , A D Wilson 3 , Sara B Stefánsdóttir 4 , Edwin Tijhaar 5 , Sigridur Jonsdottir 1 , Rebekka Frey 6 , Dania Reiche 7 , Horst Rose 7 , Claudio Rhyner 8 , Gertraud Schüpbach-Regula 1 , Sigurbjörg Torsteinsdottir 4 , Marcos Alcocer 2 , Eliane Marti 1
Affiliations

1 Department of Clinical Research and VPH, Vetsuisse Faculty, University of Bern, Switzerland.
2 School of Biosciences, University of Nottingham, Loughborough, UK.
3 Division of Veterinary Pathology, Infection and Immunity, University of Bristol, Langford, UK.
4 Institute for Experimental Pathology, Biomedical Center, University of Iceland, Reykjavik, Iceland.
5 Cell Biology and Immunology Group, Wageningen University, De Elst 1, 6708 WD, Wageningen, The Netherlands.
6 AniCura Norsholms Djursjukhus, Norsholm, Sweden.
7 Boehringer Ingelheim Vetmedica GmbH, Germany.
8 Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.

Abstract
Background: 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 aims to test a comprehensive panel of differently expressed Culicoides r-allergens on a cohort of IBH-affected and control horses using an allergen microarray.

Methods: IgE levels to 27 Culicoides r-allergens, including 8 previously unpublished allergens, of which 11 were expressed in more than one expression system, were determined in sera from 347 horses.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 sero-positivity 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.

Results: Sero-positivity was significantly higher in IBH horses compared to 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).

Conclusion: This microarray will be a powerful tool for 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.