ABSTRACT
BACKGROUND: Anti-α6ß4 integrin autoantibodies can be observed in some patients with mucous membrane pemphigoid. We have previously identified anti-α6ß4 integrin extracellular domain autoantibodies together with anti-BP180 NC16A antibodies in a patient with DPP-4 inhibitor-induced bullous pemphigoid. However, the significance and impact of anti-α6ß4 integrin antibodies are unknown. OBJECTIVES: To characterize anti-α6ß4 integrin extracellular domain autoantibodies in pemphigoid patients, to determine whether these antibodies inhibit laminin-α6ß4 integrin binding and to observe their systemic effects. METHODS: Anti-α6ß4 integrin autoantibodies were analysed by staining cells expressing the extracellular region of α6ß4 integrin with sera from 20 patients with pemphigoid. The anti-α6ß4 integrin autoantibodies were characterized using different transfectants. The binding of laminins to α6ß4 integrin was studied using cells expressing the activated conformation of α6ß4 integrin and the inhibitory effect of the autoantibodies on the binding of laminins to α6ß4 integrin was tested. Trends in antibody titres and clinical symptoms were quantified and analysed. RESULTS: IgG autoantibodies against the extracellular domain of anti-α6ß4 integrin were found in some patients with pemphigoid. Laminin binding to α6ß4 integrin was observed in the active conformation of α6ß4 integrin, and serum from a patient with a high titre of anti-α6ß4 integrin antibodies inhibited the binding of both laminin-511 and laminin-332 to α6ß4 integrin. α6ß4 integrin is expressed on the basement membrane of both skin and small intestine, and exfoliation was observed in the patient's epidermis and small intestinal epithelium. A reduction in the titre of the anti-α6ß4 integrin antibody was associated with improvement in both skin and gastrointestinal symptoms. CONCLUSIONS: This study demonstrated the presence of anti-α6ß4 integrin extracellular domain-specific autoantibodies in some patients with pemphigoid. In addition, these autoantibodies showed inhibitory activity on α6ß4 integrin-laminin binding. Anti-α6ß4 integrin antibodies can affect the gastrointestinal tract as well as the skin and oral mucosa.
