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. 2024 May 1:15:1356300.
doi: 10.3389/fneur.2024.1356300. eCollection 2024.

IL-6 receptor antibody treatment improves muscle weakness in experimental autoimmune myasthenia gravis mouse model

Shota Miyake  1 , Kenichi Serizawa  1 , Shinichi Onishi  1 , Yoshichika Katsura  1 , Masayuki Baba  1 , Mitsue Kurasawa  1 , Haruna Tomizawa-Shinohara  1 , Keigo Yorozu  1 , Yoshihiro Matsumoto  1 , Mariko Noguchi-Sasaki  1
Affiliations

IL-6 receptor antibody treatment improves muscle weakness in experimental autoimmune myasthenia gravis mouse model

Shota Miyake et al. Front Neurol. .

Abstract

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG.

Keywords: IL-6; IL-6R antibody; acetylcholine receptor; follicular helper T cells; myasthenia gravis.

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Conflict of interest statement

SM, KS, SO, YK, MB, MK, HT-S, KY, YM, and MN-S were employed by Chugai Pharmaceutical Co., Ltd.

Figures

Figure 1
Figure 1
Effect of IL-6 receptor antibody (MR16-1) treatment on muscle weakness in AChR-immunized mice. Grip strength was measured every week in mice from the CFA-treated control group (black circles), AChR-immunized group (red squares), and AChR-immunized + MR16-1-treated group (blue triangles) (n = 10 per group). Data are presented as mean ± SD. ***p < 0.001 by two-way ANOVA.
Figure 2
Figure 2
Effect of IL-6 receptor antibody treatment on deposition of anti-AChR IgG in muscle in AChR-immunized mice. (A) Co-localization of mouse IgG and AChR in the tibialis anterior muscle was detected by co-staining with anti-mouse IgG (green) and alpha-bungarotoxin (red). Nuclear DNA was stained with DAPI (4′,6-diamidino-2-phenylindole) (blue). (B) Mouse IgG-positive area as a percentage of AChR area was quantified by using HALO AI imaging analysis software in CFA-treated control group (black circles), AChR-immunized group (red squares) and, AChR-immunized + MR16-1-treated group (blue triangles) (n = 10 per group). Data are presented as mean ± SD. **p < 0.01, ***p < 0.001 by Tukey’s multiple comparison test.
Figure 3
Figure 3
Effects of IL-6 receptor antibody treatment on levels of AChR autoantibodies in serum. Anti-mouse AChR IgG (A) and IgG subclasses (B) in serum samples from the CFA-treated control group (black circles), AChR-immunized group (red squares), and AChR-immunized + MR16-1-treated group (blue triangles) were measured by ECL (n = 10 per group). Data are presented as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001 by Steel–Dwass’s multiple comparison test.
Figure 4
Figure 4
Effects of IL-6 receptor antibody treatment on immunophenotype in lymph nodes. Immunophenotyping of EAMG mouse in lymph nodes (A–G) of Naive (black squares), CFA-treated group (black circles), AChR-immunized group (red squares), and AChR-immunized + MR16-1-treated group (blue triangles) (n = 5 per group). Data are presented as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001 by Tukey’s multiple comparison test.
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