Immunopathogenesis and immunotherapy of Culicoides hypersensitivity in horses: an update

Abstract

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.

Aspergillus fumigatus binding IgA and IgG1 are increased in bronchoalveolar lavage fluid of horses with neutrophilic asthma

“…A clear preference to use single allergens over crude extract in serology has been determined for equine Culicoides hypersensitivity, but was not indicated here for EA using eight selected A. fumigatus antigens ( 25 ). The different A. fumigatus antigens tested here were mainly similar to each other regarding their immunogenicity.…”

“…However, their advantage over A. fumigatus lysate as an antigen source for IgG and IgA serology was small in this study. It is possible that IgA- and IgG-inducing A. fumigatus antigens detected in this approach are more diverse than IgE-inducing allergens ( 25 , 73 ). A lack of dominating A. fumigatus antigens in EA would complicate antigen-specific therapeutic strategies as well as diagnostics.…”

“…It is unclear if A. fumigatus allergens defined by human IgE reactivity are also the dominant immunogens for horses, or if there is a general dominance of single antigens in EA as implied by equine IgE binding profiles on several available allergen preparations ( 19 , 22 ). Dominance of single allergens has been described in equine allergy to Culicoides salivary allergens, and in this context, the use of pure major allergens for serologic diagnostics is advantageous for accuracy compared to the use of mixtures like extracts ( 25 ). A. fumigatus lysate or extracts that are commonly used for serology contain a broad mixture of antigens without defined allergen concentrations ( 19 , 22 , 26 , 27 ).…”

Autoimmune disorders in horses: the role of Insect Bite Hypersensitivity

“…When an allergic subject with prior exposure to the allergen, on re-exposure to the allergen, there is cross-linking of IgE bound to high affinity FcεRI receptors on mast cells leading to release of different mediators, causing the clinical signs of immediate hypersensitivity. Infiltration of leucocytes such as T helper 2 (Th2) cells, eosinophils and basophils at the site of the allergic reaction is followed by late-phase reaction peaking 24 h post exposure (Marti et al, 2021). Furthermore, with regards to earlier studies on the immunopathology of IBH, they was reported increase in the population of CD4+, Langerhans, and eosinophil cells in the skin (McKelvie et al, 1999).…”

“…Under the effect of these cytokines, antigen presenting cells (APC) direct the immune response towards the production of IL-4 and IL-13 with the help of helper T cell (Th)2. Subsequently, B cells undergo class switch to produce allergen-specific IgE that binds to high affinity FcεRI receptors on mast cells and basophils leading to sensitization (Marti et al, 2021). When an allergic subject with prior exposure to the allergen, on re-exposure to the allergen, there is cross-linking of IgE bound to high affinity FcεRI receptors on mast cells leading to release of different mediators, causing the clinical signs of immediate hypersensitivity.…”