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

6 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
JournalJournal of Investigative Dermatology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Linear IgA Bullous Dermatosis
Vancomycin
Immunoglobulin A
Collagen Type VII
Pharmaceutical Preparations
Serum
Enzyme-Linked Immunosorbent Assay
Autoantigens
Indirect Fluorescent Antibody Technique
Basement Membrane
Skin
Density (optical)
Fluorescence Microscopy
Autoantibodies
Autoimmune Diseases
Microscopic examination
Membrane Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis. / Yamagami, Jun; Nakamura, Yoshio; Nagao, Keisuke; Funakoshi, Takeru; Takahashi, Hayato; Tanikawa, Akiko; Hachiya, Takahisa; Yamamoto, Toshiyuki; Ishida-Yamamoto, Akemi; Tanaka, Toshihiro; Fujimoto, Noriki; Nishigori, Chikako; Yoshida, Tetsuya; Ishii, Norito; Hashimoto, Takashi; Amagai, Masayuki.

In: Journal of Investigative Dermatology, 01.01.2018.

Research output: Contribution to journalArticle

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. https://doi.org/10.1016/j.jid.2017.12.035
Yamagami, Jun ; Nakamura, Yoshio ; Nagao, Keisuke ; Funakoshi, Takeru ; Takahashi, Hayato ; Tanikawa, Akiko ; Hachiya, Takahisa ; Yamamoto, Toshiyuki ; Ishida-Yamamoto, Akemi ; Tanaka, Toshihiro ; Fujimoto, Noriki ; Nishigori, Chikako ; Yoshida, Tetsuya ; Ishii, Norito ; Hashimoto, Takashi ; Amagai, Masayuki. / Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis. In: Journal of Investigative Dermatology. 2018.
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