title: Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, Harvard Medical School, Center for Neurologic Disease, Brigham and Women's Hospital, Harvard Institutes of Medicine, Rm. 780, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
authors.forename: Sucheep
authors.initials: S
authors.lastname: Piyasirisilp
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Samia
authors.initials: S
authors.lastname: Khoury
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
mesh_terms: D000915:Antibody Affinity / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011863:Radioimmunoassay
chemical_list: D001323:Autoantibodies; D004676:Myelin Basic Protein