IgG4 autoantibodies induce dermal–epidermal separation

S Mihai, MT Chiriac, JE Herrero-González, M Goodall, R Jefferis, Caroline Savage, D Zillikens, C Sitaru

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Bullous pemphigoid (BP) is a sub-epidermal autoimmune blistering disease associated with autoantibodies to the dermal - epidermal junction (DEJ). Patients' autoantibodies induce dermal - epidermal separation when co-incubated with cryosections of human skin and leucocytes from healthy volunteers. IgG autoantibodies trigger complement and/or leucocyte activation resulting in specific pathology in several autoimmune conditions. In these diseases, IgG1 and IgG3 isotypes, but not the IgG4 subclass, are thought to trigger inflammatory pathways resulting in tissue damage. The capacity of IgG4 autoantibodies to mediate tissue damage has not yet been demonstrated. In this study, we isolated IgG1 and IgG4 autoantibodies from bullous pemhigoid patients' serum and analysed their blister-inducing potential in our cryosection assay. As expected, complement-fixing IgG1 autoantibodies induced sub-epidermal splits in this experimental model. Purified IgG4 did not fix complement, but, interestingly, like IgG1, activated leucocytes and induced dermal - epidermal separation. The potential of IgG4 autoantibodies to induce Fc-dependent dermal - epidermal separation was significantly lower compared to IgG1. Our results demonstrate that IgG4 autoantibodies are able to activate leucocytes and point to a hitherto less recognized function of IgG4. Moreover, for the first time, we clearly demonstrate that BP IgG4 autoantibodies have the capacity to induce leucocyte-dependent tissue damage.
Original languageEnglish
Pages (from-to)1117-28
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume11
Issue number5
DOIs
Publication statusPublished - 1 Sep 2007

Keywords

  • complement
  • inflammation
  • neutrophils
  • autoimmunity

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