Autoantibodies of non‐inflammatory bullous pemphigoid hardly deplete type <scp>XVII</scp> collagen of keratinocytes

Imafuku, Kimiaki; Iwata, Hiroaki; Kamaguchi, Mayumi; Izumi, Kiyotaka; Natsuga, Ken; Ujiie, Hideyuki; Nishie, Wataru; Shimizu, Hiroshi

doi:10.1111/exd.13331

Cited by 15 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports demonstrated that BP180 C‐term‐IgG does not show pathogenicity in vivo nor in vitro . We next studied the effects of Fc‐binding proteins on mAb C17‐C1 targeting the C‐terminus of BP180.…”

Section: Resultsmentioning

confidence: 99%

Fc‐binding proteins enhance autoantibody‐induced BP180 depletion in pemphigoid

Iwata

Kamaguchi

Ujiie

et al. 2019

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Immunoglobulins (Igs) consist of two antigen‐binding regions (Fab) and one constant region (Fc). Protein A and protein G are bacterial proteins used for the purification of IgG by virtue of their high affinities for the Fc fragment. Rheumatoid factors are autoantibodies against IgG Fc fragments, which are present in the body under physiological conditions. Little is known about the influence of Fc‐binding proteins on the pathogenicity of antibody‐induced autoimmune diseases. Pemphigoid diseases are a group of autoimmune subepidermal blistering disorders that includes bullous pemphigoid and mucous membrane pemphigoid. IgGs targeting the non‐collagenous NC16A domain of the 180‐kDa bullous pemphigoid antigen (BP180) are known to induce skin fragility in mice and the depletion of BP180 in keratinocytes. In this study, mAb against NC16A in combination with Fc‐binding proteins was found to enhance BP180 depletion. Although mAb against the C‐terminus of BP180 does not show pathogenicity in vivo or in vitro, mAb treatment with Fc‐binding proteins clearly induced skin fragility in mice and BP180 depletion in keratinocytes. Anti‐BP180 mAbs and Fc‐binding proteins were colocalized in the cytoplasm and at the basement membrane zone. Cell adhesion strengths were decreased in parallel with BP180 amounts. Clinically, bullous pemphigoid patients had higher rheumatoid factor titers than controls. Anti‐BP180 mAb in combination with high‐titer rheumatoid factor serum was found to enhance BP180 depletion. Furthermore, saliva from mucous membrane pemphigoid patients contained larger quantities of bacteria and Fc‐binding proteins than controls. Our results suggest that Fc‐binding proteins (rheumatoid factor or protein G) may enhance the pathogenicity of autoantibodies in pemphigoid diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

show abstract

Section: Resultsmentioning

confidence: 99%

Fc‐binding proteins enhance autoantibody‐induced BP180 depletion in pemphigoid

Iwata

Kamaguchi

Ujiie

et al. 2019

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The amount of COL17 in the TritonX‐100‐soluble fraction (ie non‐hemidesmosomal COL17) was found to be decreased at 6 hours after BP‐IgG stimulation, and that in the TritonX‐100‐insoluble fraction (ie hemidesmosomal COL17) was found to be decreased at 48 hours. COL17 depletion was observed in the setting of stimulation with anti‐NC16A BP‐IgG, but not with non‐NC16A BP‐IgG (Figure B, right).…”

Section: Evidence Of Non‐complement Relevancementioning

confidence: 96%

Complement‐independent blistering mechanisms in bullous pemphigoid

Iwata

Ujiie

2017

Experimental Dermatology

Self Cite

View full text Add to dashboard Cite

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that clinically demonstrates tense blisters with widespread erythema, histologically demonstrates subepidermal blistering and immunologically demonstrates the presence of circulating autoantibodies against hemidesmosomal molecules. Complement activation has long been regarded as necessary for the generation of the BP. However, certain evidence has recently come to support non-complemental blistering mechanisms.The story of BP blistering mechanisms is a complicated one. This review mainly focuses on a specific blistering mechanism that highlights the role of complements in BP blistering. K E Y W O R D Sbullous pemphigoid, collagen XVII, complement

show abstract

“…Studies showing that antibodies targeting areas outside of NC16A had less capacity to deplete COL17 on keratinocytes than antibodies targeting NC16A suggest that the pathogenicity of autoantibodies in BP could be epitope dependent 61, 62 . Recent studies have offered some biomarkers for more efficient diagnosis and prediction of prognosis in pemphigoid 63, 64 .…”

Section: Pemphigoidmentioning

confidence: 99%

Recent advances in the understanding and treatment of pemphigus and pemphigoid

Yamagami¹

2018

F1000Res

View full text Add to dashboard Cite

Pemphigus and pemphigoid are characterized as autoimmune blistering diseases in which immunoglobulin G autoantibodies cause blisters and erosions of the skin or mucosa or both. Recently, understanding of the pathophysiology of pemphigus and pemphigoid has been furthered by genetic analyses, characterization of autoantibodies and autoreactive B cells, and elucidation of cell–cell adhesion between keratinocytes. For the management of pemphigus and pemphigoid, the administration of systemic corticosteroids still represents the standard treatment strategy; however, evidence of the efficacy of therapies not involving corticosteroids, such as those employing anti-CD20 antibodies, is increasing. The goal should be to develop antigen-specific immune suppression-based treatments.

show abstract

Autoantibodies of non‐inflammatory bullous pemphigoid hardly deplete type XVII collagen of keratinocytes

Cited by 15 publications

References 25 publications

Fc‐binding proteins enhance autoantibody‐induced BP180 depletion in pemphigoid

Fc‐binding proteins enhance autoantibody‐induced BP180 depletion in pemphigoid

Complement‐independent blistering mechanisms in bullous pemphigoid

Recent advances in the understanding and treatment of pemphigus and pemphigoid

Contact Info

Product

Resources

About