TY - JOUR
T1 - Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions
AU - O'Connor, Kevin C.
AU - Chitnis, Tanuja
AU - Griffin, Diane E.
AU - Piyasirisilp, Sucheep
AU - Bar-Or, Amit
AU - Khoury, Samia
AU - Wucherpfennig, Kai W.
AU - Hafler, David A.
PY - 2003/3
Y1 - 2003/3
N2 - The presence of autoantibodies to the immunodominant antigen, myelin basic protein (MBP), in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) has been poorly characterized. Many studies report detectable levels of autoantibodies to myelin basic protein though other studies, using similar techniques, report their absence. We compared a solution-phase assay that has detected clinically relevant autoantibodies in diabetes and other autoimmune diseases to solid phase assays similar to those used in previous reports. The solution-phase assay consistently measured autoantibodies to MBP in serum from human subjects with Semple rabies vaccine (SRV)-induced demyelinating disease and from MBP-immunized animals. A solid phase assay detected MBP autoantibodies in the serum of a fraction of patients with MS. Autoantibodies capable of binding to MBP in the solution-phase were not detected in the CSF or serum of patients with MS. Additional solution-phase measurements revealed that anti-MBP antibodies from individuals with SRV-induced demyelinating disease demonstrated a binding affinity profile consistent with that of polyclonal antibodies with a range of affinities from low to high. In contrast, antibodies to MBP in the serum of MS patients detected by ELISA did not bind soluble MBP in the same assay. These results indicate that the humoral response in patients with MS does not include moderate- or high-affinity autoantibodies to MBP.
AB - The presence of autoantibodies to the immunodominant antigen, myelin basic protein (MBP), in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) has been poorly characterized. Many studies report detectable levels of autoantibodies to myelin basic protein though other studies, using similar techniques, report their absence. We compared a solution-phase assay that has detected clinically relevant autoantibodies in diabetes and other autoimmune diseases to solid phase assays similar to those used in previous reports. The solution-phase assay consistently measured autoantibodies to MBP in serum from human subjects with Semple rabies vaccine (SRV)-induced demyelinating disease and from MBP-immunized animals. A solid phase assay detected MBP autoantibodies in the serum of a fraction of patients with MS. Autoantibodies capable of binding to MBP in the solution-phase were not detected in the CSF or serum of patients with MS. Additional solution-phase measurements revealed that anti-MBP antibodies from individuals with SRV-induced demyelinating disease demonstrated a binding affinity profile consistent with that of polyclonal antibodies with a range of affinities from low to high. In contrast, antibodies to MBP in the serum of MS patients detected by ELISA did not bind soluble MBP in the same assay. These results indicate that the humoral response in patients with MS does not include moderate- or high-affinity autoantibodies to MBP.
KW - Antibodies
KW - Autoimmunity
KW - Diabetes
KW - EAE/MS
KW - Human
KW - Myelin basic protein
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U2 - 10.1016/S0165-5728(03)00002-X
DO - 10.1016/S0165-5728(03)00002-X
M3 - Article
C2 - 12620653
AN - SCOPUS:0037333270
VL - 136
SP - 140
EP - 148
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
IS - 1-2
ER -