Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis

Jun Yamagami, Yoshio Nakamura, Keisuke Nagao, Takeru Funakoshi, Hayato Takahashi, Akiko Tanikawa, Takahisa Hachiya, Toshiyuki Yamamoto, Akemi Ishida-Yamamoto, Toshihiro Tanaka, Noriki Fujimoto, Chikako Nishigori, Tetsuya Yoshida, Norito Ishii, Takashi Hashimoto, Masayuki Amagai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Vancomycin (VCM) is known to induce linear IgA bullous dermatosis (LAD). However, in contrast to conventional LAD, in which circulating IgA autoantibodies against basement membrane proteins are commonly detected, patient sera from VCM-induced LAD yields negative results in indirect immunofluorescence microscopy, and the targeted autoantigen remains undetermined. By using sera from a typical patient with VCM-induced LAD, we identified that co-incubation of sera with VCM resulted in linear IgA deposition at the basement membrane zone by indirect immunofluorescence. Patient sera reacted with the dermal side of 1 mol/L NaCl-split skin and with the recombinant noncollagenous (i.e., NC1) domain of type VII collagen by both immunoblot and ELISA in the presence of VCM. The investigation of an additional 13 patients with VCM-induced LAD showed that 10 out of the 14 sera (71.4%) reacted with the NC1 domain of type VII collagen by ELISA when spiked with VCM, whereas only 4 (28.6%) tested positive without it. The enhancement of reactivity to NC1 by VCM, as determined by optical density via ELISA, was observed in 10 out of the 14 sera (71.4%). These findings indicate that type VII collagen is a target autoantigen in VCM-induced LAD and that VCM mediates IgA autoreactivity against type VII collagen, providing an insight into mechanisms involved in drug-induced autoimmune disease.

Original languageEnglish
Pages (from-to)1473-1480
Number of pages8
JournalJournal of Investigative Dermatology
Volume138
Issue number7
DOIs
Publication statusPublished - 2018 Jul

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Yamagami, J., Nakamura, Y., Nagao, K., Funakoshi, T., Takahashi, H., Tanikawa, A., Hachiya, T., Yamamoto, T., Ishida-Yamamoto, A., Tanaka, T., Fujimoto, N., Nishigori, C., Yoshida, T., Ishii, N., Hashimoto, T., & Amagai, M. (2018). Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis. Journal of Investigative Dermatology, 138(7), 1473-1480. https://doi.org/10.1016/j.jid.2017.12.035