title: Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid.
abstract: Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activation, has been reported to be involved in several autoimmune diseases. In the present study, we investigated whether CD46 plays a role in BP development. We found that sCD46 expression was significantly increased in the serum and blister fluids of BP patients and correlated with the levels of anti-BP180 NC16A antibody and C3a. Otherwise, the level of mCD46 was decreased in lesions of BP patients, whereas the complement activation was enhanced. We also found that CD46 knockdown in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. Importantly, exogenous CD46 blocked complement activation in both healthy skin sections and keratinocytes induced by exposure to pathogenic antibodies from BP patients. These data suggest that CD46 deficiency is an important factor in BP pathogenesis and that increasing CD46 levels might be an effective treatment for BP.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Qiao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Erle
authors.initials: E
authors.lastname: Dang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. xjwgang@fmmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000378:metabolism*; D016022:Case-Control Studies; D002460:Cell Line; D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D015926:Complement C3a