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 syst em associated with inflammation and gliosis, may be on autoimmune disease w ith T lymphocytes and autoantibodies to myelin protein(s). This study deals exclusively with B cell autoimmunity to myelin basic protein (MBP). T lymp hocytes and anti-MBP shore a common MBP epitope located between P-85 and P- 96 which contains the essential contact residues H88FFK91 for the trimolecu lar complex. The purpose of this Phase I open label clinical study was to m onitor CSF anti-MBP in patients with chronic progressive MS subsequent to I V administration of synthetic Peptide (sp) MBP82-98 namely DEN85VVHFFKNIVTP 96RT. Fifty-six patients who participated in this project were assigned to two groups a 'control group' of 15 patients who received IV saline injectio ns 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 a nd then infrequently subsequent to a rise of their CSF anti-MBP. In the con trol group antibody levels remained persistently elevated during the 2 year period. Patients in the 'peptide group' segregated into four kinetic profi les: 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 pa tients) showed significant CSF anti-MBP suppression after the initial injec tion but lost the ability to suppress the autoantibody titer following subs equent 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 '.