Immunopathogenesis and immunotherapy of Culicoides hypersensitivity in horses: an update

Culicoides hypersensitivity (CH) is a strongly pruritic dermatitis of horses, characterised histologically by mixed perivascular to diffuse cellular infiltrates of mononuclear cells and eosinophils, and caused by helper T cell (Th)2, immunoglobulin (Ig)E-mediated reactions to antigens present in the saliva of biting Culicoides midges. As treatment of CH is still not satisfactory, a better knowledge of the pathogenesis of CH is needed for the development of new therapeutic modalities. Accordingly, availability of pure Culicoides allergens instead of crude whole body extracts is essential for the improvement of in vitro diagnosis of CH and development of a more effective allergen immunotherapy (AIT). Beside the Th2 cytokines interleukin (IL)-4 and IL-13, recent studies have shown the involvement of thymic stromal lymphopoietin, IL-5 and IL-31 in the pathogenesis of CH. The importance of IL-5 and IL-31 has been confirmed through targeting these cytokines by active immunisation of CH patients, resulting in a significant decrease of CH lesion scores. Thirty Culicoides salivary allergens have been described over the last 10 years and produced as pure recombinant (r-) proteins. Use of a protein microarray has allowed the identification of the most relevant Culicoides r-allergens for CH in central and northern Europe. An immunisation protocol has been developed for preventive AIT against CH. Small amounts of r-Culicoides allergens injected into the submandibular lymph nodes with Alum/MPLA as adjuvants seem to induce a suitable immune response for both preventive and therapeutic AIT. The next years will reveal whether these recent advancements will translate into an improved diagnosis, treatment and prevention of CH.