Bullous pemphigoid suggestive of complement‐independent blister formation with anti‐
            <scp>BP</scp>
            180 IgG4 autoantibodies

Dainichi, Teruki; Nishie, Wataru; Yamagami, Yoshie; Sonobe, H.; Ujiie, Hideyuki; Kaku, Yo; Kabashima, Kenji

doi:10.1111/bjd.14411

Cited by 32 publications

(38 citation statements)

References 15 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We also reported that IgG4 autoantibodies to BP180 can induce blister formation in mice in a complement‐independent manner . Furthermore, a recent study described non‐inflammatory BP cases with the deposition of IgG4 autoantibodies but not complements . Thus, the mild clinical phenotype of BP230‐type BP in our cases may be associated with the predominance of the IgG4 subclass.…”

Section: Discussionsupporting

confidence: 64%

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

Zheng

Ujiie

Iwata

et al. 2018

Acad Dermatol Venereol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 64%

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

Zheng

Ujiie

Iwata

et al. 2018

Acad Dermatol Venereol

Self Cite

View full text Add to dashboard Cite

show abstract

“…That BP could not develop without activation of the complement system has been questioned by the report of a C4‐deficient patient with BP; the finding that in two cases of complement‐negative BP, IgG4 antibodies with limited complement‐fixing ability were the dominant antibody; and the fact that IgG4 antibodies have been reported to predominate in BP, especially in complement‐negative patients with BP . Experimental studies have described complement‐independent mechanisms that could play a role in the pathophysiology of BP.…”

Section: Laboratory Results For Patients With and Without C3mentioning

confidence: 99%

“…8 Other crucial complement-dependent mechanisms described are mast cell activation and degranulation, 9 and neutrophil attraction and activation, secreting neutrophil elastase and matrix metalloproteinase (MMP)-9 cleaving murine BP180. 10 That BP could not develop without activation of the complement system has been questioned by the report of a C4-deficient patient with BP; 11 the finding that in two cases of complement-negative BP, IgG4 antibodies with limited complement-fixing ability were the dominant antibody; 12 and the fact that IgG4 antibodies have been reported to predominate in BP, 13 especially in complement-negative patients with BP. 14 Experimental studies have described complementindependent mechanisms that could play a role in the pathophysiology of BP.…”

mentioning

confidence: 99%

Complement in bullous pemphigoid: results from a large observational study

et al. 2016

View full text Add to dashboard Cite

“…Subsequent studies using monoclonal antibodies have raised the possibility that some autoantibodies are capable of inducing blister formation in the absence of complement [41, 42]. A recent report describes two cases of BP with dominant IgG4 and without C3 deposition at the BMZ, indicating that blister formation could be complement-independent in some BP cases [43]. However, it is well documented that the majority of human BP skin (>90%) have complement (C3 deposition), and less than 10% of BP patients are C3-negative at the basement membrane zone by direct IF [44, 45].…”

Section: Discussionmentioning

confidence: 99%

IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid

Zuo

Evangelista

Culton

et al. 2016

Journal of Autoimmunity

View full text Add to dashboard Cite

The IgG4 subclass of antibodies exhibits unique characteristics that suggest it may function in an immunoregulatory capacity. The inhibitory function of IgG4 has been well documented in allergic disease by the demonstration of IgG4 blocking antibodies, but similar functions have not been explored in autoimmune disease. Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease characterized by autoantibodies directed against BP180 and an inflammatory infiltrate including eosinophils and neutrophils. Animal models have revealed that the NC16A region within BP180 harbors the critical epitopes necessary for autoantibody mediated disease induction. BP180 NC16A-specific IgG belong to the IgG1, IgG3, and IgG4 subclasses. The purpose of this study was to determine effector functions of different IgG subclasses of NC16A-specific autoantibodies in BP. We find that IgG4 anti-NC16A autoantibodies inhibit the binding of IgG1 and IgG3 autoantibodies to the NC16A region. Moreover, IgG4 anti-NC16A blocks IgG1 and IgG3 induced complement fixation, neutrophil infiltration, and blister formation clinically and histologically in a dose-dependent manner following passive transfer to humanized BP180-NC16A mice. These findings highlight the inhibitory role of IgG4 in autoimmune disease and have important implications for the treatment of BP as well as other antibody mediated inflammatory and autoimmune diseases.

show abstract

Bullous pemphigoid suggestive of complement‐independent blister formation with anti‐ BP 180 IgG4 autoantibodies

Cited by 32 publications

References 15 publications

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

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

Complement in bullous pemphigoid: results from a large observational study

IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid

Contact Info

Product

Resources

About