Clinical and immunological profiles of anti-BP230-type bullous pemphigoid: Restriction of epitopes to the C-terminal domain of BP230, shown by novel ELISAs of BP230-domain specific recombinant proteins

Objectives: To confirm that sera from some BP patients reactive exclusively to the BP230 and to study the clinical and immunological characteristics of this condition. Materials and methods: BP patients were divided into three groups: BP reactive only to BP230 (BP230-BP), BP reactive to both BP180 and BP230 (BP180-BP230-BP) and BP reactive only to BP180 (BP180-BP), based on the results of standard ELISAs for BP180 and BP230. Clinical features were statistically analyzed among the three groups. Then, targeted epitopes in each group were studied by immunoblotting and novel ELISAs using three domain-specific BP230 recombinant proteins. Results: Forty-one, 65 and 47 of 153 BP patients were categorized as BP230-BP, BP180-BP230-BP and BP180-BP, respectively. Clinically, BP230-BP patients showed significantly lower severity, less need of systemic steroids and better responses to various treatments, suggesting that BP230-BP is a milder condition. Immunoblotting and ELISAs of domain-specific BP230 recombinant proteins indicated that, while BP180-BP230-BP sera reacted with all three domains of BP230, BP230-BP sera reacted more frequently with epitopes in the BP230 C-terminal domain. Conclusion: We propose a new disease entity, named anti-BP230-type BP, in which anti-BP230 antibodies might be pathogenic and react specifically with the BP230 C-terminal domain. While anti-BP230 antibodies in BP180-BP230-BP seem to be produced via intermolecular epitope spreading, anti-BP230 antibodies in BP230-BP are considered to be produced by different mechanisms.