Kinetic profiles of cerebrospinal fluid anti-MBP in response to intravenous MBP synthetic peptide DENP85VVHFFKNIVTP96RT in multiple sclerosis patients

Multiple sclerosis [MS] a demyelinating disease of the central nervous system associated with inflammation and gliosis, may be on autoimmune disease with T lymphocytes and autoantibodies to myelin protein(s). This study deals exclusively with B cell autoimmunity to myelin basic protein (MBP). T lymphocytes and anti-MBP shore a common MBP epitope located between P-85 and P-96 which contains the essential contact residues H88FFK91 for the trimolecular complex. The purpose of this Phase I open label clinical study was to monitor CSF anti-MBP in patients with chronic progressive MS subsequent to IV administration of synthetic Peptide (sp) MBP82-98 namely DEN85VVHFFKNIVTP96RT. Fifty-six patients who participated in this project were assigned to two groups a 'control group' of 15 patients who received IV saline injections every 6 months for the first 2 years of the study and a 'peptide group' of 41 patients who received IV spMBP82-98 from the beginning of the study and then infrequently subsequent to a rise of their CSF anti-MBP. In the control group antibody levels remained persistently elevated during the 2 year period. Patients in the 'peptide group' segregated into four kinetic profiles: Cohort A (15 patients) illustrated prolonged anti-BMP suppression into the normal range. Cohort B (10 patients) illustrated significant anti-MBP suppression into the normal range for shorter durations. Cohort C (eight patients) showed significant CSF anti-MBP suppression after the initial injection but lost the ability to suppress the autoantibody titer following subsequent injections. Cohort D (eight patients) foiled to show significant CSF anti-MBP suppression. In conclusion the B eel tolerizing effect of sPMBP82-98 segregated into four kinetic profiles this molecular variability should be considered in attempts to develop specific 'peptide therapies' for the broad range of clinical profiles currently diagnosed as 'multiple sclerosis'.