A CROSS-REACTIVE ANTIMYELIN BASIC-PROTEIN IDIOTOPE IN CEREBROSPINAL-FLUID CELLS IN MULTIPLE-SCLEROSIS

We wanted to find evidence of antibody to myelin basic protein (MBP) i n patients with MS by detecting their shared usage of immunoglobulin g enes. As demonstrated by the idiotopes (Id) of murine monoclonal antib ody to peptides of MBP, there is limited use of the variable (V) regio n immunoglobulin genes for the immune response in mice to this encepha litogenic protein. Cross-reactive Ids have been detected across differ ent murine strains and shared by T and B cells. One cross-reactive Id, designated as 845D3 Id, is located on the V region of kappa light cha ins of two murine monoclonal antibodies, one to MBP peptide 80-89 and the other to MBP peptide acetyl 1-9. To examine the occurrence of 845D 3 Id in MS, we used the V region of a light chain (V-L) of one of the monoclonal antibodies to probe the V-L genes expressed in B cells in C SF of 50 patients (31 MS and 19 non-MS). The V-L genes expressed in B cells found in CSF were amplified by polymerase chain reaction using u niversal human V-region primers. The 845D3 Id probe detected the Id(+) V region in the CSF of 14 of 31 MS patients, 1 of 9 patients with oth er neurologic diseases, and 1 of 10 non-neurologic patients. The gene product was more common in but not restricted to CSF with oligoclonal bands. The presence in CSF of MS patients of a cross-reactive Id to di fferent MBP peptides is indicative of an immune response to this encep halitogenic myelin protein in a segment of MS patients. These findings are also evidence for limited usage of V-region Ig genes in the immun e response of humans to MBP and the possible importance of an Id netwo rk for MBP in demyelinating disease.