Equine bullous pemphigoid IgG autoantibodies target linear epitopes in the NC16A ectodomain of collagen XVII (BP180, BPAG2).

The research investigates an autoimmune condition found in horses, similar to Bullous pemphigoid in humans, where IgG autoantibodies wrongly target certain components of the skin, causing blisters and ulcers. The study provides proof that these autoantibodies are targeting a specific component of the skin architecture, namely the NC16A ectodomain of collagen XVII, thus indicating the condition as another example of an autoimmune dermatosis in humans.

Research Objectives and Methods

• The researchers aimed to understand the pathological mechanisms underlying a condition in horses that led to skin and mucosal ulcers and microscopic subepithelial vesiculation. This condition had pathological features similar to bullous pemphigoid (BP), an autoimmune skin condition in humans, dogs, cats, and pigs.
• The study involved two horses exhibiting the above mentioned condition. The researchers used direct and indirect immunofluorescence tests to examine skin biopsies and to determine the presence of autoantibodies. Epithelial substrates were also used to locate the target of the autoantibodies.
• In order to confirm the findings, Immunoblotting and ELISA were performed to establish the immunoreactivity against the specific component of the skin, the NC16A extracellular domain of type XVII collagen.

Key Findings

• The direct immunofluorescence revealed the presence of IgG autoantibodies lining the basement membrane region where the dermis and epidermis meet. This indicated an autoimmune response against the individual’s own tissues.
• Using intact and salt-split epithelial substrates, the study demonstrated that IgG antibodies target not just the basal, but also lateral and apical parts of the stratum basale keratinocytes.
• Immunoblotting and ELISA revealed that IgG from affected horses exhibited high immunoreactivity against the NC16A ectodomain of collagen XVII. This immunoreactivity was not present in unaffected (control) horses. This suggests that in the affected horses’ immune system, this protein domain is wrongly recognized as a foreign substance, leading to an autoimmune response.

Significance and Implications

• The research successfully identified the specific skin component that the IgG autoantibodies in horses with the condition target, the NC16A extracellular domain of type XVII collagen, closely aligning the equine condition with human Bullous pemphigoid.
• This raises the possibility of equine bullous pemphigoid being another spontaneous model of human basement membrane autoimmune dermatosis, potentially expanding avenues for further research and treatment options for like conditions in humans.