Suppression of the CD28/B7 pathway reduces the occurrence and development of myasthenia gravis and cytokine levels

Abstract

Background

Myasthenia gravis (MG) is an antibody-mediated, autoimmune neuromuscular disease. Reports have indicated that the CD28/B7 ligand interactions play a crucial role during primary immune responses. Hence, the aim of the present study was to investigate the possible effects of the CD28/B7 pathway on the occurrence and development of MG and its associated cytokine factors.

Methods

An experimental autoimmune myasthenia gravis (EAMG) was initially established by immunization of Lewis rats with acetylcholine receptor (AChR) α97-116 peptide. Then the rats were treated with dexamethasone and CTLA4-Ig (used for inhibiting the CD28/B7 pathway). Serum levels of AChR IgG and AChR IgG2b were then detected using ELISA. The clinical features, muscle contraction function, AChR content, expression of CD28, CTLA4, B7.1 and B7.2 in mononuclear cells of peripheral blood and the secretion of cytokines (INF-γ, IL-2, IL-10 and IL-12) in serum of rats were measured. Finally, lymphocyte proliferation upon CTLA4 IgG treatment was examined in vitro.

Results

Inhibition of the CD28/B7 pathway and dexamethasone were found to significantly improve clinical symptoms of EAMG rats, reduce serum levels of AChR IgG, AChR IgG2b, INF-γ, IL-2, IL-10 and IL-12, the expression of CD28, CTLA4, B7.1 and B7.2 in mononuclear cells of peripheral blood, and enhance muscle contraction function and AChR content in the muscle in vivo. Meanwhile, CTLA4 IgG could abolish the increased lymphocyte proliferation following AChR stimulation in vitro.

Conclusion

Overall, the suppression of the CD28/B7 pathway by CTLA4-Ig can have the potential to retard the occurrence and development of MG.

Keywords:

• Myasthenia gravis
• CD28/B7 pathway
• EAMG
• CTLA4-Ig
• Lymphocyte proliferation
• AChR
• Cytokine expression

Acknowledgments

We would like to show our sincerest appreciation to the reviewers and their critical comments on this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author’s contributions

ZXX and YSG designed the study. XLW collated the data, YSG carried out data analyses and produced the initial draft of the manuscript. ZXX and XLW contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

Consent for publication

Consent for publication was obtained from the participants.

Availability of data and material

The datasets generated during the current study are available.

Additional information

Funding

This study was supported by the Outstanding Youth Fund in Hebei Province Department of Education (No. Y2012002) and Natural Science Foundation of Hebei Province (No. H2012405016).