Kinetic profiles of cerebrospinal fluid anti-MBP in response to intravenous MBP synthetic peptide DENP(85)VVHFFKNIVTP(96)RT in multiple sclerosis patients.
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 P(85) and P(96) which contains the essential contact residues H(88)FFK(91) 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 DEN(85)VVHFFKNIVTP(96)RT. 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'. Multiple Sclerosis (2000) 6 300 - 311
Warren
K G
KG
Department of Medicine, Multiple Sclerosis Patient Care and Research Clinic, University of Alberta, Edmonton, Alberta Canada, TG6 2G3.
Catz
I
I
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D015331:Cohort Studies; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007165:Immunosuppression Therapy; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology
D001323:Autoantibodies; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D010446:Peptide Fragments