Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jul 21:5:10809.
doi: 10.1038/srep10809.

Streptococcal IdeS: therapeutic potential for Guillain-Barré syndrome

Ryo Takahashi  1 , Nobuhiro Yuki  2
Affiliations

Streptococcal IdeS: therapeutic potential for Guillain-Barré syndrome

Ryo Takahashi et al. Sci Rep. .

Abstract

Plasma exchange and intravenous immunoglobulin are effective in treating Guillain-Barré syndrome (GBS) probably because the former removes IgG autoantibodies and complement and the latter inhibits complement activation subsequent to the autoantibody binding to peripheral nerve antigens. IgG degrading enzyme of Streptococcus pyogenes (IdeS) can cleave the pathogenic autoantibodies into F(ab')2 and Fc. The purpose of this study is to show whether IdeS has novel therapeutic potential for GBS. Sera with anti-ganglioside IgG antibodies from 15 patients with GBS or Miller Fisher syndrome were used. We tested whether IdeS cleaved the anti-ganglioside IgG antibodies and inhibited deposition of activated complement component on ELISA plates. IdeS efficiently cleaved IgG and blocked complement activation mediated by anti-GM1, anti-GD1a and anti-GQ1b IgG antibodies. IdeS has therapeutic potential for GBS and related conditions.

PubMed Disclaimer

Conflict of interest statement

Dr. Takahashi has no relevant disclosures. Prof. Yuki serves as an editorial board member of Expert Review of Neurotherapeutics, The Journal of the Neurological Sciences, The Journal of Peripheral Nervous System, Neurosurgery & Psychiatry.

Figures

Figure 1
Figure 1
(A) Schema of IdeS treatment for binding of autoantibodies. Anti-ganglioside antibodies in the diluted patients’ sera bind to the ganglioside coating on the microtiter plates. IdeS cleaves IgG antibodies into F(ab’)2 and Fc fragments. Peroxidase-conjugated anti-human IgG (Fc) does not bind to the F(ab’)2 residue and does not work as the luminescent substrate in IdeS treated plates. (B) Concentration dependence of IdeS treatment. The representative change of GM1-IgG binding depends on its concentration. The clearance of IgG (Fc) accumulated to the highest levels at a concentration of 10 μg/ml or more of IdeS. (C) Time to react after adding IdeS. The binding of GM1-IgG halved after around 10 minutes and was almost eliminated after one hour. (D) The binding of IgG was detected by ELISA with both anti-Fc and anti-F(ab’)2 antibodies. Fc deposition was degraded by IdeS (10 μg/ml), whereas F(ab’)2 deposition remained unaltered. IdeS inhibited the Fc deposition of not only anti-GM1 IgG (n = 5) but also anti-GD1a IgG (n = 5) and anti-GQ1b IgG (n = 5) antibodies. (E) The binding of IgM was detected by ELISA. IdeS did not affect the binding of anti-GM1 IgM antibodies (n = 5).
Figure 2
Figure 2
(A) Schema of IdeS treatment for complement deposition. Complement C3 deposition mediated by anti-ganglioside IgG antibodies was detected on the microtiter plates. IdeS treatment cleaved IgG autoantibodies and prevented subsequent complement activation. (B) Blocking effect of IdeS on complement deposition. IdeS blocked C3 deposition mediated by IgG autoantibodies against GM1, GD1a and GQ1b, respectively. (C) Concentration dependence of IdeS treatment. The representative change of C3 deposition mediated by GM1-IgG depends on its concentration. The blocking effect of C3 accumulated to the highest levels at a concentration of 10 μg/ml or more of IdeS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Yuki N. & Hartung HP. Guillain–Barré syndrome. N Engl J Med. 366: 2294−2304 (2012). - PubMed
    1. Yuki N. et al. Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain−Barré syndrome. Proc Natl Acad Sci USA. 101: 11404−11409 (2004). - PMC - PubMed
    1. Susuki K. et al. Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers. J Neurosci. 27: 3956−3967 (2007). - PMC - PubMed
    1. McGonigal R. et al. Anti-GD1a antibodies activate complement and calpain to injure distal motor nodes of Ranvier in mice. Brain. 133: 1944−1960 (2010). - PubMed
    1. Hafer-Macko CE. et al. Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy. Ann Neurol. 39: 625−635 (1996). - PubMed

Publication types

MeSH terms

-