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Streptococcal IdeS: therapeutic potential for Guillain-Barré syndrome.

Takahashi R, Yuki N - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

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.

No MeSH data available.


Related in: MedlinePlus

(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.
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f2: (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.

Mentions: The established assays demonstrated the binding of autoantibodies to each ganglioside and the deposition of active complement component. The detection of Fc domain was obscured due to cleavage by IdeS and subsequent rinsing out. Nevertheless F(ab’)2 remained to bind stably to the ganglioside coating on the microtiter plates (Fig. 1A and 2A). The clearance of Fc depended on the concentration of IdeS (Fig. 1B) as well as the time after the addition of IdeS to the serum (Fig. 1C). The cleaving effect emerged in a few minutes and reached the maximum in one hour. IdeS cleaved all the anti-GM1, anti-GD1a and anti-GQ1b IgG antibodies (Fig. 1D). Fc deposition was degraded by IdeS (10 μg/ml), whereas F(ab’)2 deposition remained unaltered. Thus, the subsequent complement deposition mediated by anti-ganglioside IgG autoantibodies was inhibited by IdeS, resulting in the blocking of the C3 deposition (Fig. 2B). The blocking effect depended on the concentration of IdeS as well as the clearance of Fc (Fig. 2C). In contrast, IdeS did not affect the binding of anti-GM1 IgM antibodies (Fig. 1E).


Streptococcal IdeS: therapeutic potential for Guillain-Barré syndrome.

Takahashi R, Yuki N - Sci Rep (2015)

(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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508529&req=5

f2: (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.
Mentions: The established assays demonstrated the binding of autoantibodies to each ganglioside and the deposition of active complement component. The detection of Fc domain was obscured due to cleavage by IdeS and subsequent rinsing out. Nevertheless F(ab’)2 remained to bind stably to the ganglioside coating on the microtiter plates (Fig. 1A and 2A). The clearance of Fc depended on the concentration of IdeS (Fig. 1B) as well as the time after the addition of IdeS to the serum (Fig. 1C). The cleaving effect emerged in a few minutes and reached the maximum in one hour. IdeS cleaved all the anti-GM1, anti-GD1a and anti-GQ1b IgG antibodies (Fig. 1D). Fc deposition was degraded by IdeS (10 μg/ml), whereas F(ab’)2 deposition remained unaltered. Thus, the subsequent complement deposition mediated by anti-ganglioside IgG autoantibodies was inhibited by IdeS, resulting in the blocking of the C3 deposition (Fig. 2B). The blocking effect depended on the concentration of IdeS as well as the clearance of Fc (Fig. 2C). In contrast, IdeS did not affect the binding of anti-GM1 IgM antibodies (Fig. 1E).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

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.

No MeSH data available.


Related in: MedlinePlus