Culicoides Hypersensitivity

Type I hypersensitivities, or allergies, are mediated by immunoglobulin E (IgE) which causes the release of inflammatory substances from mast cells and other effector immune cells. Horses can be allergic to a wide range of allergens, but the most common equine allergy is caused by salivary proteins from Culicoides midges. Allergy signs include itchiness, hair loss, and skin wounds. Culicoides hypersensitivity is a seasonal, recurrent disease and allergic horses only experience clinical disease during warm months when they are bit by Culicoides. They clinically recover in the winter. In horses, clinical manifestation of this allergy often occurs at 4–5 years of age, while sensitization to allergen can precede clinical signs by at least one year.

An updated summary of the immune cells involved in equine Culicoides hypersensitivity.
Many different cell types are involved in the allergic response. We have recently characterized monocytes, basophils and antibody secreting cells and their function in response to allergen and IgE activation. Figure from: Larson and Wagner (2021) Molecular Immunology.

We are currently studying the role of rare peripheral immune cells that bind IgE and respond to allergen. We have characterized antibody production, basophils and monocytes longitudinally both during allergen exposure and when the horses are clinically healthy. The goal of this work is to better understand the immune mechanism of allergy and to identify predictive biomarkers of allergy for diagnostic assay development.

We also test how maternal IgE influences allergy susceptibility in neonates. We showed that foals do not produce IgE antibodies in their first year of life. However, clearly detectable amounts of IgE are transferred from mares to offspring with the colostrum after birth.

References

  1. Viral infection and allergy - What equine immune responses can tell us about disease severity and protection

    Larson EM, Wagner B

    Mol Immunol. 2021 Jul;135:329-341. doi: 10.1016/j.molimm.2021.04.013. Epub 2021 May 8.

  2. IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy

    Larson EM, Babasyan S, Wagner B

    J Immunol. 2021 May 15;206(10):2312-2321. doi: 10.4049/jimmunol.2001354. Epub 2021 May 5.

  3. Peripheral blood basophils are the main source for early interleukin-4 secretion upon in vitro stimulation with Culicoides allergen in allergic horses

    Raza F, Babasyan S, Larson EM, Freer HS, Schnabel CL, Wagner B

    PLoS One. 2021 May 26;16(5):e0252243. doi: 10.1371/journal.pone.0252243.

  4. Cul o 2 specific IgG3/5 antibodies predicted Culicoides hypersensitivity in a group imported Icelandic horses

    Raza F, Ivanek R, Freer H, Reiche D, Rose H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Wagner B

    BMC Vet Res. 2020 Aug 10;16(1):283. doi: 10.1186/s12917-020-02499-w.

  5. Phenotype and function of IgE-binding monocytes in equine Culicoides hypersensitivity

    Larson EM, Babasyan S, Wagner B

    PLoS One. 2020 May 22;15(5):e0233537. doi: 10.1371/journal.pone.0233537.

  6. Comparison of three clinical scoring systems for Culicoides hypersensitivity in a herd of Icelandic horses

    Miller JE, Mann S, Fettelschoss-Gabriel A, Wagner B

    Vet Dermatol. 2019 Dec;30(6):536-e163. doi: 10.1111/vde.12784. Epub 2019 Aug 22.

  7. Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IgE on subpopulations of IgM+ and IgG1+ B-cells in horses

    Wagner B, Hillegas JM, Babasyan S

    Vet Immunol Immunopathol. 2012 Apr 15;146(2):125-34. doi: 10.1016/j.vetimm.2012.02.007. Epub 2012 Feb 18.

  8. Induction of interleukin-4 production in neonatal IgE+ cells after crosslinking of maternal IgE

    Wagner B, Stokol T, Ainsworth DM

    Dev Comp Immunol. 2010 Apr;34(4):436-44. doi: 10.1016/j.dci.2009.12.002. Epub 2009 Dec 16.

  9. Sensitization of skin mast cells with IgE antibodies to Culicoides allergens occurs frequently in clinically healthy horses

    Wagner B, Miller WH Jr, Erb HN, Lunn DP, Antczak DF

    Vet Immunol Immunopathol. 2009 Nov 15;132(1):53-61. doi: 10.1016/j.vetimm.2009.09.015. Epub 2009 Sep 23.

  10. IgE in horses: occurrence in health and disease

    Wagner B

    Vet Immunol Immunopathol. 2009 Nov 15;132(1):21-30. doi: 10.1016/j.vetimm.2009.09.011. Epub 2009 Sep 23. Review.

  11. A histamine release assay to identify sensitization to Culicoides allergens in horses with skin hypersensitivity

    Wagner B, Childs BA, Erb HN

    Vet Immunol Immunopathol. 2008 Dec 15;126(3-4):302-8. doi: 10.1016/j.vetimm.2008.09.001. Epub 2008 Sep 11.

  12. A comparison of intradermal testing and detection of allergen-specific immunoglobulin E in serum by enzyme-linked immunosorbent assay in horses affected with skin hypersensitivity

    Morgan EE, Miller WH Jr, Wagner B

    Vet Immunol Immunopathol. 2007 Dec 15;120(3-4):160-7. Epub 2007 Aug 19.

  13. Occurrence of IgE in foals: evidence for transfer of maternal IgE by the colostrum and late onset of endogenous IgE production in the horse

    Wagner B, Flaminio JB, Hillegas J, Leibold W, Erb HN, Antczak DF

    Vet Immunol Immunopathol. 2006 Apr 15;110(3-4):269-78. Epub 2005 Dec 15.