title: IgG-degrading enzyme of Streptococcus pyogenes (IdeS) prevents disease progression and facilitates improvement in a rabbit model of Guillain-Barré syndrome.
abstract: Autoantibodies binding to peripheral nerves followed by complement deposition and membrane attack complex formation results in nerve damage in Guillain-Barré syndrome (GBS). Strategies to remove the pathogenic autoantibodies or block the complement deposition benefit most patients with GBS. Immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) is a cysteine protease which cleaves IgG antibodies into F(ab')2and Fc fragments. In this study, using a rabbit model of axonal GBS, acute motor axonal neuropathy (AMAN), we demonstrated that IdeS treatment significantly reduced the disruption of Nav channels as well as activated C3 deposition at the anterior spinal root nodes of Ranvier in AMAN rabbits. IdeS significantly promoted the clinical recovery of AMAN rabbits and there were significant lower frequencies of axonal degeneration in anterior spinal roots of AMAN rabbits with IdeS treatment compared to the saline controls. Our data support that IdeS treatment is a promising therapeutic strategy for GBS.
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China; Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Qiguang
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Graduate School of Tianjin Medical University, Tianjin 300071, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Quanquan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Qiao
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Zhanyun
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Hansa Medical AB, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Kjellman
authors.affiliation: Hansa Medical AB, Lund, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Järnum
authors.affiliation: Hansa Medical AB, Lund, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Winstedt
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, People's Republic of China. Electronic address: yanleihao301@live.com.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Neurology, Mishima Hospital, Niigata, Japan. Electronic address: gbs.yuki.cidp@gmail.com.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yuki
mesh_terms: D000818:Animals; D001323:Autoantibodies; D001426:Bacterial Proteins / Q000276:immunology* / Q000627:therapeutic use*; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005677:G(M1) Ganglioside / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000276:immunology / Q000628:therapy*; D007074:Immunoglobulin G / Q000097:blood / Q000627:therapeutic use*; D009431:Neural Conduction / Q000502:physiology; D011817:Rabbits; D011901:Ranvier's Nodes / Q000378:metabolism / Q000473:pathology; D015222:Sodium Channels / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D001426:Bacterial Proteins; D003176:Complement C3; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus; D015222:Sodium Channels; D005677:G(M1) Ganglioside
keywords: Acute motor axonal neuropathy; Guillain-Barré syndrome; IgG clearance; Immunoglobulin G-degrading enzyme of Streptococcus pyogenes