Warren K G, Catz I
Department of Medicine, Multiple Sclerosis Patient Care and Research Clinic, University of Alberta, Edmonton, Alberta Canada, TG6 2G3.
Mult Scler. 2000 Oct;6(5):300-11. doi: 10.1177/135245850000600502.
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
多发性硬化症（MS）是一种与炎症和胶质增生相关的中枢神经系统脱髓鞘疾病，可能是一种由T淋巴细胞和针对髓鞘蛋白的自身抗体引起的自身免疫性疾病。本研究专门探讨B细胞对髓鞘碱性蛋白（MBP）的自身免疫。T淋巴细胞和抗MBP共享一个位于P(85)和P(96)之间的共同MBP表位，该表位包含三分子复合物的关键接触残基H(88)FFK(91)。这项I期开放标签临床研究的目的是监测慢性进行性MS患者静脉注射合成肽（sp）MBP82-98（即DEN(85)VVHFFKNIVTP(96)RT）后脑脊液中的抗MBP。参与该项目的56名患者被分为两组：“对照组”15名患者，在研究的前两年每6个月接受一次静脉注射生理盐水；“肽组”41名患者，从研究开始就接受静脉注射spMBP82-98，然后在脑脊液抗MBP升高后不频繁注射。在对照组中，抗体水平在2年期间持续升高。“肽组”的患者分为四种动力学模式：A组（15名患者）显示抗BMP抑制作用延长至正常范围。B组（10名患者）显示抗MBP显著抑制作用在较短时间内进入正常范围。C组（8名患者）在初次注射后显示脑脊液抗MBP显著抑制，但在随后的注射后失去了抑制自身抗体滴度的能力。D组（8名患者）未显示脑脊液抗MBP显著抑制。总之，spMBP82-98的B细胞耐受作用分为四种动力学模式；在试图为目前诊断为“多发性硬化症”的广泛临床特征开发特定的“肽疗法”时，应考虑这种分子变异性。《多发性硬化症》（2000年）6 300 - 311
