Examination of characteristics that may distinguish disease-causing from benign AChR-reactive antibodies in experimental autoimmune myasthenia gravis.
In summary, the strategies of the experimentation described above were designed to address the confusion resulting from observations concerning the lack of correlation between antibody titers and disease severity in MG patients. Lessons learned from these studies of EAMG suggest that if the proportion of the total expressed/produced anti-AChR antibody repertoire with disease-causing potential differs from patient-to-patient with MG, then assessment of the total antibody titer becomes meaningless unless a particular patient produces disease-causing reactivities that make up a major portion of the total titer. Not only may disease severity depend on the titer of a small subset of disease-causing antibody(s) reactive with a particular conformation-dependent AChR region, but may also depend on the relative contribution of additional subsets of antibody with functionally irrelevant or potentially protective activity. The key to exploiting the existence of antibody subsets with differing disease-causing potential will be to create probes that would allow the easy monitoring of the relevant reactivities. For instance, carefully selected anti-idiotypic antibodies (such as the 11E10 monoclonal antibody described above) may be of great value when specifically capable of recognizing idiotypes that are selectively associated with disease-causing anti-AChR antibodies and under-represented on antibodies lacking disease-causing capability. If, in addition, characteristics of helper T cells are identified that allow more accurate prediction of D+ Id production, exciting opportunities would become available to more directly evaluate disease mechanisms and to develop more highly efficacious immunotherapeutic strategies.
Krolick
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KA
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284-7758, USA.
Zoda
T E
TE
Thompson
P A
PA
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D011978:Receptors, Nicotinic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D011978:Receptors, Nicotinic