Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.
J Neuroinflammation. 2012 Apr 26;9:80. doi: 10.1186/1742-2094-9-80.
In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established.
We prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients' sera.
After the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA.
IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.
在多发性硬化症的复发中，静脉注射皮质类固醇治疗无效时，建议进行血浆置换。免疫吸附（IA）被认为是一种替代疗法，但它的疗效和潜在作用机制仍需确定。
我们前瞻性地治疗了 11 名患有视神经炎且符合血浆置换治疗适应证的多发性硬化症患者（试验注册 DE/CA25/00007080-00）。共进行了五次色氨酸免疫吸附治疗。在免疫吸附治疗前后及治疗后 6 个月，通过视力、扩展残疾状况量表（EDSS）、失能状况量表（ISs）测量临床活动，通过视觉诱发电位测量实验室值。此外，还进行了蛋白质组学分析，以分析柱结合蛋白以及患者血清中相应的变化。
第三次免疫吸附治疗后，我们发现 11 名患者中的 8 名视力改善，我们将这 8 名患者称为应答者。其中，8 名应答者的平均视力从基线时的 0.15±0.12 提高到第三次免疫吸附后的 0.47±0.32（P=0.0252），到免疫吸附治疗后 180±10 天提高到 0.89±0.15（P<0.0001）。应答者的可溶性白细胞介素 2 受体降低（P=0.03），而非应答者的白细胞介素 2 受体没有降低。免疫吸附柱吸附的蛋白质的蛋白质组学分析显示，几种重要的免疫蛋白以及中枢神经系统蛋白片段，包括髓鞘碱性蛋白，已被免疫吸附清除。
IA 治疗皮质类固醇难治性视神经炎有效。IA 影响体液免疫反应。然而，令人惊讶的是，我们发现强有力的证据表明，脱髓鞘产物和免疫调节剂也通过 IA 从血浆中清除。
