Immunomodulation by a dual altered peptide ligand of autoreactive responses to the acetylcholine receptor of peripheral blood lymphocytes of patients with myasthenia gravis

Human Immunology
M DayanEdna Mozes

Abstract

Myasthenia gravis (MG) is a T cell-dependent, antibody-mediated autoimmune disease. A dual altered peptide ligand (APL) that is composed of the tandemly arranged two single amino acid analogs of two myasthenogenic peptides was demonstrated to downregulate in vitro and in vivo murine MG associated autoreactive responses. Furthermore, treatment with the dual APL ameliorated the clinical manifestations of an established experimental autoimmune MG in mice. This study was undertaken in order to investigate the ability of the dual APL to immunomodulate MG-associated responses of peripheral blood lymphocytes (PBL) of patients with MG to the native autoantigen acetylcholine receptor (AChR). PBL of 22 of 27 patients with MG tested responded by proliferation to torpedo AChR. The proliferative responses of PBL of 21 of 22 responders were significantly inhibited by the dual APL. The inhibition was specific because a control peptide did not inhibit these proliferative responses. The dual APL also downregulated the levels of the secreted pathogenic cytokine IFN-gamma in supernatants of stimulated PBL of 80% of the tested patients. The latter inhibitions correlated with an upregulated production of the immunosuppressive cytokine, tumor growth...Continue Reading

References

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Citations

Nov 3, 2006·The Journal of Clinical Investigation·Bianca M Conti-FineHenry J Kaminski
Jul 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Badiga Venkata ArunaEdna Mozes
Aug 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Michael Sela, Edna Mozes
Dec 14, 2005·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Ru LiZhanguo Li
Jan 5, 2006·Autoimmunity·Erica Lee, Animesh A Sinha

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