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

Department of Medicine, Multiple Sclerosis Patient Care and Research Clinic, University of Alberta, Edmonton, Alberta Canada, TG6 2G3, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada, TG6 2G3

Ingrid Catz

Department of Medicine, Multiple Sclerosis Patient Care and Research Clinic, University of Alberta, Edmonton, Alberta Canada, TG6 2G3, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada, TG6 2G3

Multiple sclerosis [MS], a demyelinating disease of the central nervous system associated with inflammation and gliosis, may be an 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 share a common MBP epitope located between P₈₅ and P₉₆ 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) failed to show significant CSF anti-MBP suppression. In conclusion the B cell 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'.

Key Words: multiple sclerosis • anti-MBP • autoimmunity • synthetic peptides • tolerance

Multiple Sclerosis, Vol. 6, No. 5, 300-311 (2000)
DOI: 10.1177/135245850000600502


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