Baumhefner R W, Tourtellotte W W, Syndulko K, Shapshak P, Osborne M, Rubinshtein G
Neurology Service, VA Wadsworth Medical Center, Los Angeles, CA 90073.
Neurology. 1988 Jul;38(7 Suppl 2):69-72.
One of the hallmarks of multiple sclerosis (MS) is intra-blood-brain-barrier (BBB) IgG synthesis, a byproduct of plasma cells located in and around active inflammatory demyelinating plaques. The rate of IgG synthesis can be measured by plugging CSF and blood IgG and albumin concentrations into our equation. When done in conjunction with CSF and serum analyses for IgG oligoclonal bands, 99% of definite MS patients demonstrate intra-BBB IgG synthesis. At autopsy the pathologic criterion of an inactive plaque of demyelination is absence of inflammatory cells. Hence, we propose that modulation downward or eradication of intra-BBB IgG synthesis (ie, a manifestation of reduced white matter inflammation) in a living patient is a reasonable therapeutic criterion and goal of MS therapy. In a preliminary trial of five severely disabled MS patients, we evaluated the effects of copolymer 1 (COP-1) in daily intramuscular doses of 20 mg (2 patients) and twice daily subcutaneous doses of 15 mg (3 patients) on clinical parameters and on intra-BBB IgG synthesis over a 2-month study period. The results of this trial showed no beneficial effect on neurologic function or on inflammatory demyelination, as assessed by monitoring of intra-BBB IgG synthesis.
多发性硬化症（MS）的一个标志是血脑屏障（BBB）内IgG合成，这是位于活跃炎性脱髓鞘斑块内及周围的浆细胞产生的副产物。IgG合成速率可通过将脑脊液（CSF）和血液中的IgG及白蛋白浓度代入我们的公式来测量。若与CSF及血清中IgG寡克隆带分析同时进行，99%的确诊MS患者会出现血脑屏障内IgG合成。尸检时，非活动性脱髓鞘斑块的病理标准是无炎性细胞。因此，我们提出，在活体患者中下调或消除血脑屏障内IgG合成（即白质炎症减轻的一种表现）是MS治疗合理的治疗标准和目标。在一项针对5名严重残疾MS患者的初步试验中，我们评估了每日肌肉注射20mg（2名患者）和每日皮下注射两次、每次15mg（3名患者）的共聚肽1（COP-1）在为期2个月的研究期间对临床参数及血脑屏障内IgG合成的影响。通过监测血脑屏障内IgG合成评估，该试验结果显示对神经功能或炎性脱髓鞘无有益作用。
