Vancomycin mediates IgA autoreactivity in drug-induced linear IgA bullous dermatosis.

5 years ago

Vancomycin mediates IgA autoreactivity in drug-induced linear IgA bullous dermatosis.

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

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 (vLAD) yields negative results in indirect immunofluorescence microscopy, and the targeted autoantigen remains undetermined. By utilizing sera from a typical case of vLAD, we identified that co-incubation of sera with VCM resulted in linear IgA deposition at the basement membrane zone (BMZ) by indirect immunofluorescence. Patient sera reacted with the dermal side of 1M NaCl-split skin and with the recombinant noncollagenous (NC1) domain of type VII collagen (COL7) by both immunoblot and ELISA in the presence of VCM. The investigation of an additional 13 cases of vLAD revealed that 10 out of the 14 sera (71.4%) reacted with NC1 domain of COL7 by ELISA when spiked with VCM, while only 4 (28.6%) were 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 COL7 is a target autoantigen in vLAD, and that VCM mediates IgA autoreactivity against COL7, providing an insight into mechanisms involved in drug-induced autoimmune disease.

Publisher URL: http://doi.org/10.1016/j.jid.2017.12.035

DOI: 10.1016/j.jid.2017.12.035