Characteristics of IgG subclasses and complement deposition in BP230‐type bullous pemphigoid

Abstract

Background Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP180 is the primary autoantigen of BP, and in a portion of BP cases, BP230 is the only target of autoantibodies. Such BP is called BP230‐type BP. BP230‐type BP tends to show milder clinical phenotypes than conventional BP, but the reason is unclear. The pathogenic roles of autoantibodies and complement activation have been shown in conventional BP, but the distribution of IgG subclasses and the degree of complement deposition in BP230‐type BP remain unclear. Objective To compare the distribution of IgG subclasses and the degree of complement deposition in BP230‐type BP with those in conventional BP with autoantibodies to BP180 and BP230 (BP180‐BP230‐type BP). Methods The diagnosis of BP was confirmed by the histopathology of the lesions, the deposition of IgG and complement in the perilesional skin and the presence of circulating autoantibodies to BP180 and BP230. The disease severity was determined by bullous pemphigoid disease area index. The deposition of IgG subclasses and complement deposition were examined by direct immunofluorescence of the perilesional skin in 6 BP230‐type BP cases and 11 BP180‐BP230‐type BP cases. Results Sixty seven percent of BP230‐type BP cases show a mild clinical phenotype. All BP230‐type BP cases and 82% of BP180‐BP230‐type BP cases were found to demonstrate the clear deposition of IgG4 at the basement membrane zone of skin specimens. Notably, the deposition of IgG1 and IgG3 was faint or negative in all of the BP230‐type BP cases, whereas they were clearly detected in 91% and 64% of the BP180‐BP230‐type BP cases, respectively. The deposition of complement C3 tended to be weaker in BP230‐type BP than in BP180‐BP230‐type BP. Conclusion The mild clinical phenotype of BP230‐type BP may correlate with the weaker deposition of IgG1, IgG3 and complement in the skin lesions.

The pathogenesis of bullous skin diseases

“…These studies support the dominant role of anti-BP180 autoantibodies compared with anti-BP230 autoantibodies in the pathogenesis of BP. There are approximately 8% of BP cases where only anti-BP230 antibodies are found, and this is referred to as BP230-type BP [ 136 ].…”

Review of autoimmune blistering diseases: the Pemphigoid diseases

“…Antibodies that target BP 180 at the NC16A domain result in inflammatory BP but non‐NC16A targets result in a non inflammatory presentation, where there is an absence of urticaria and erythema . The BP230 subtype of BP, where the BP 230 is the only autoantigen targeted, typically presents with milder disease than the classic BP . Classically, patients have weeks to months of pruritus, urticaria or eczema followed by symmetric tense bullae on urticated, erythematous or normal skin on the trunk, inner thigh and flexures.…”

“…23 The BP230 subtype of BP, where the BP 230 is the only autoantigen targeted, typically presents with milder disease than the classic BP. 24 Classically, patients have weeks to months of pruritus, urticaria or eczema followed by symmetric tense bullae on urticated, erythematous or normal skin on the trunk, inner thigh and flexures. Atypical presentations include an absence of blisters in up to 20% of cases, chronic itch with urticaria or eczematous eruptions, prurigo nodules and excoriations (Figs.…”

Risk Factors for Mucosal Involvement in Bullous Pemphigoid and the Possible Mechanism: A Review

“…Based on these findings, it is reasonable to speculate that some triggers of BP may induce the release of autoantibodies against BP180 epitopes other than NC16A. And the presence of anti-BP230 antibodies brings several particular clinical features of BP (63). However, the aforementioned studies have demonstrated that patients who lacked anti-BP230 antibodies were prone to mucosal lesions (13).…”