017 Endotypes of mucous membrane pemphigoid predict disease severity

Mucous membrane pemphigoid (MMP) is an autoimmune bullous disease predominantly involving mucosae and is caused by autoantibodies directed against BP180, Collagen VII, Laminin 332, or α6β4 integrin. Oral/pharyngeal lesions are the most common, but any mucous membrane can be involved. The potential long-term consequences are devasting, including blindness, airway compromise, loss of dentition and strictures. Despite its morbidity, therapies specific for MMP have not been developed. Our goal was to determine if MMP can be resolved into distinct disease endotypes based on the autoantibody target. Seventy-one patients who met clinical, histological and immunologic criteria for MMP were enrolled prospectively. Demographics, clinical information, and course of the disease were all recorded. Sera were obtained and the relevant antigen was determined using a combination of indirect immunofluorescence, ELISAs and immunoblotting. BP180 was the most common primary autoantibody target, identified in 51 patients (73.5%) followed by α6β4 in 5 (7.4%), COLVII in 4 (5.9%), and LAM332 in 3 (4.4%). Autoantibodies targeting LAM332 or COLVII predicted more severe disease that was associated with an increased number of sites affected, involvement of high-risk sites (larynx, eye), need for rituximab for disease control, and a decrease in long-term remission. A propensity for specific sites of involvement based on target autoantigen (LAM332/larynx, COLVII/ocular) was also observed, but was not exclusive. Our findings suggest that MMP can be sorted into endotypes based on the autoantibody target. These endotypes can improve disease outcomes by facilitating selection of the most efficacious treatment and will aid in the development of type-specific targeted therapies.