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Current treatments and developments in pemphigoid diseases as paradigm diseases for autoantibody-driven, organ-specific autoimmune diseases.
Seminars in Hematology 2016 April
Pemphigoid diseases constitute a group of difficult-to-treat, remitting-relapsing autoimmune skin diseases. They are autoantibody-driven diseases with well-defined autoantigens in the hemidesmosomal complex at the dermal-epidermal junction (DEJ). Autoantibody deposition initiates the recruitment of granulocytes to the DEJ, where these cells degrade the hemidesmosomal complex, disrupting dermal-epidermal adherence, which clinically manifests as blisters and erosions. Due to their well-defined autoantigens and the location at the body surface, allowing the direct observation of inflammation throughout its course, pemphigoid diseases are excellent paradigm diseases to study the pathomechanisms of autoantibody-driven diseases. Current treatments of pemphigoid diseases largely rely on systemic immunosuppression despite the restriction of inflammation to the skin. The iatrogenic immunosuppression may contribute to the high 1-year mortality rate in pemphigoid diseases. Thus, the overall survival does not depend on the extent of skin lesions before treatment, but depends on whether topical or systemic glucocorticoid application is initially used. Systemic glucocorticoid application is linked to higher mortality than topical application, illustrating that systemic immunosuppression can harm the overall prognosis and that immunomodulatory treatment strategies are required. New mouse models of pemphigoid diseases have been instrumental in approaching the introduction of novel immunomodulatory therapies in the treatment of autoimmune diseases.
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