Integrin β4 is a major target antigen in pure ocular mucous membrane pemphigoid

Background: Previous studies of ocular mucous membrane pemphigoid (OMMP) have identified several components of the basement membrane zone to be autoantigens, including integrin beta 4. However, there are no extensive or definitive reported studies that address this, particularly in pure OMMP. Objectives: To clarify the major autoantigens in pure OMMP. Materials and methods: In this study, we examined sera from 43 pure OMMP patients for both IgG and IgA antibodies using newly developed immunoblotting analyses with a hemidesmosome-rich fraction and various recombinant proteins of integrin alpha 6 beta 4, in addition to our routine immune-serological tests. Results: Using a hemidesmosome-rich fraction, sera from patients with pure OMMP demonstrated reactivity of IgG and/or IgA antibodies to integrin beta 4, BP180 and laminin-332. The reactivity of pure OMMP sera to integrin beta 4 was further confirmed by immunoblotting using integrin beta 4 recombinant proteins. Using concentrated supernatant of HaCaT cells, only one serum sample showed positive IgG and IgA reactivity to LAD-1, the ectodomain of BP180. None of the pure OMMP sera reacted with any autoantigens on immunoblotting using normal human epidermal or dermal extracts, or purified human laminin-332. Conclusions: Integrin beta 4 was considered to be the major and specific autoantigen for pure OMMP. The new methods established in this study are useful for detection of various autoantigens, particularly integrin beta 4.