Modulation of the anti-acetylcholine receptor response and experimental autoimmune myasthenia gravis by recombinant fragments of the acetylcholine receptor

Dora Barchan, Orna Asher, Socrates J. Tzartos, Sara Fuchs, Miriam C. Souroujon

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

Myasthenia gravis (MG) is a neuromuscular disorder of man caused by a humoral response to the acetylcholine receptor (AChR). Most of the antibodies in MG and in experimental autoimmune myasthenia gravis (EAMG) are directed to the extracellular portion of the AChR a subunit, and within it, primarily to the main immunogenic region (MIR). We have cloned and expressed recombinant fragments, corresponding to the entire extracellular domain of the AChR α subunit (Hα1-210), and to portions of it that encompass either the MIR (Hα1-121) or the ligand binding site of AChR (Hα122-210), and studied their ability to interfere with the immunopathological anti-AChR response in vitro and in vivo. All fragments were expressed as fusion proteins with glutathione S-transferase. Fragments Hα1-121 and Hα1-210 protected AChR in TE671 cells against accelerated degradation induced by the anti-MIR monoclonal antibody (mAb)198 in a dose-dependent manner. Moreover, these fragments had a similar effect on the antigenic modulation of AChR by other anti-MIR mAb and by polyclonal rat anti-AChR antibodies. Fragments Hα1-121 and Hα1-210 were also able to modulate in vivo muscle AChR loss and development of clinical symptoms of EAMG, passively transferred to rats by mAb 198. Fragment Hα122-210 did not have such a protective activity. Our results suggest that the appropriate recombinant fragments of the human AChR may be employed in the future for antigen-specific therapy of myasthenia.

שפה מקוריתאנגלית
עמודים (מ-עד)616-624
מספר עמודים9
כתב עתEuropean Journal of Immunology
כרך28
מספר גיליון2
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - פבר׳ 1998

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