Anti-α6β4 integrin autoantibodies inhibit the binding of laminins to α6β4 integrin in patients with pemphigoid and affect the gastrointestinal tract

被引：2

作者：

Arase, Noriko ^{[1
,8
]}

Sasaoka, Yusuke ^{[1
]}

Narita, Jun ^{[2
]}

Kiyohara, Eiji ^{[1
]}

Hashimoto, Kazuhisa ^{[2
]}

Shinzaki, Shinichiro ^{[3
,4
]}

Nojima, Satoshi ^{[5
]}

Takagi, Junichi ^{[6
]}

Fujimoto, Manabu ^{[1
,7
,8
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Dermatol, Osaka, Japan

[2] Osaka Univ, Grad Sch Med, Dept Pediat, Osaka, Japan

[3] Osaka Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Osaka, Japan

[4] Hyogo Med Univ, Sch Med, Dept Gastroenterol, Nishinomiya, Hyogo, Japan

[5] Osaka Univ, Grad Sch Med, Dept Pathol, Osaka, Japan

[6] Osaka Univ, Inst Prot Res, Lab Prot Synth & Express, Osaka, Japan

[7] Osaka Univ, Immunol Frontier Res Ctr, Lab Cutaneous Immunol, Osaka, Japan

[8] Osaka Univ, Grad Sch Med, Dept Dermatol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

来源：

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY | 2024年 / 38卷 / 02期

基金：

日本学术振兴会;

关键词：

EPIDERMOLYSIS-BULLOSA; SUBEPIDERMAL BLISTERS; PYLORIC ATRESIA; ANTIBODIES; IDENTIFICATION; EXPRESSION; MUTATIONS; BETA-4; TARGET; ITGB4;

D O I：

10.1111/jdv.19582

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Background: Anti-alpha 6 beta 4 integrin autoantibodies can be observed in some patients with mucous membrane pemphigoid. We have previously identified anti-alpha 6 beta 4 integrin extracellular domain autoantibodies together with anti-BP180 NC16A antibodies in a patient with DPP-4 inhibitor-induced bullous pemphigoid. However, the significance and impact of anti-alpha 6 beta 4 integrin antibodies are unknown.Objectives: To characterize anti-alpha 6 beta 4 integrin extracellular domain autoantibodies in pemphigoid patients, to determine whether these antibodies inhibit laminin-alpha 6 beta 4 integrin binding and to observe their systemic effects.Methods: Anti-alpha 6 beta 4 integrin autoantibodies were analysed by staining cells expressing the extracellular region of alpha 6 beta 4 integrin with sera from 20 patients with pemphigoid. The anti-alpha 6 beta 4 integrin autoantibodies were characterized using different transfectants. The binding of laminins to alpha 6 beta 4 integrin was studied using cells expressing the activated conformation of alpha 6 beta 4 integrin and the inhibitory effect of the autoantibodies on the binding of laminins to alpha 6 beta 4 integrin was tested. Trends in antibody titres and clinical symptoms were quantified and analysed.Results: IgG autoantibodies against the extracellular domain of anti-alpha 6 beta 4 integrin were found in some patients with pemphigoid. Laminin binding to alpha 6 beta 4 integrin was observed in the active conformation of alpha 6 beta 4 integrin, and serum from a patient with a high titre of anti-alpha 6 beta 4 integrin antibodies inhibited the binding of both laminin-511 and laminin-332 to alpha 6 beta 4 integrin. alpha 6 beta 4 integrin is expressed on the basement membrane of both skin and small intestine, and exfoliation was observed in the patient's epidermis and small intestinal epithelium. A reduction in the titre of the anti-alpha 6 beta 4 integrin antibody was associated with improvement in both skin and gastrointestinal symptoms.Conclusions: This study demonstrated the presence of anti-alpha 6 beta 4 integrin extracellular domain-specific autoantibodies in some patients with pemphigoid. In addition, these autoantibodies showed inhibitory activity on alpha 6 beta 4 integrin-laminin binding. Anti-alpha 6 beta 4 integrin antibodies can affect the gastrointestinal tract as well as the skin and oral mucosa.

引用

页码：404 / 412

页数：9

共 35 条

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