Biogen Idec Inc., Cambridge, MA 02142, USA.
Mult Scler. 2013 Jun;19(7):912-9. doi: 10.1177/1352458512467502. Epub 2012 Dec 11.
Natalizumab, a highly effective treatment for multiple sclerosis (MS) and Crohn's disease, is associated with progressive multifocal leukoencephalopathy (PML). Upon suspicion or diagnosis of PML, plasma exchange (PLEX) is performed to remove natalizumab from the circulation, allowing immune reconstitution of the central nervous system. Since PLEX may also remove other circulating antibodies, we examined the effects of PLEX on serum immunoglobulin (IgG) and anti-JC virus (JCV) antibody levels in MS patients with and without PML.
Serum samples from 12 natalizumab-treated patients without PML collected before, during and after PLEX were tested for IgG isotypes using a commercial assay, and for anti-JCV antibodies using a two-step enzyme-linked immunosorbent assay. Five natalizumab-treated PML patients who underwent PLEX were also tested for anti-JCV antibodies.
PLEX produced a two- to three-fold reduction in all IgG isotypes. Among patients without PML, 42% (five of 12 patients) had detectable anti-JCV antibodies before PLEX; in these patients, anti-JCV antibodies were reduced approximately two- to five-fold, with levels returning to 50-100 percent of baseline two weeks after the final PLEX. The five PML patients, all of whom had detectable anti-JCV antibodies before PLEX, experienced similar reductions in anti-JCV antibody levels following PLEX.
Our results indicate that PLEX effectively removes circulating antibodies; however, levels of endogenous anti-JCV antibody, unlike exogenously administered natalizumab, were replenished relatively quickly following PLEX. While interpretation of anti-JCV antibody levels during or within two weeks after PLEX may be problematic, humoral JCV immunity is not abolished by PLEX and antibody levels are rapidly restored.
那他珠单抗是一种治疗多发性硬化症（MS）和克罗恩病（Crohn's disease）的高效药物，但与进行性多灶性白质脑病（PML）相关。怀疑或诊断为 PML 后，进行血浆置换（PLEX）以将那他珠单抗从循环中清除，从而使中枢神经系统的免疫重建。由于 PLEX 也可能清除其他循环抗体，因此我们研究了 PLEX 对 PML 伴或不伴 PML 的 MS 患者血清免疫球蛋白（IgG）和抗 JCV 抗体水平的影响。
使用商业检测试剂盒检测 12 例未发生 PML 的那他珠单抗治疗患者在 PLEX 前后的 IgG 同种型，使用两步酶联免疫吸附试验检测这些患者和 5 例接受 PLEX 的 PML 患者的抗 JCV 抗体。
PLEX 使所有 IgG 同种型减少了两到三倍。在未发生 PML 的患者中，42%（12 例患者中有 5 例）在 PLEX 前可检测到抗 JCV 抗体；在这些患者中，抗 JCV 抗体减少了两到五倍，在最后一次 PLEX 后两周，其水平恢复到基线的 50-100%。5 例 PML 患者在 PLEX 前均检测到抗 JCV 抗体，在 PLEX 后其抗 JCV 抗体水平也出现了类似的下降。
我们的结果表明 PLEX 可有效清除循环抗体；然而，与外源性给予的那他珠单抗不同，内源性抗 JCV 抗体在 PLEX 后相对较快地得到补充。虽然在 PLEX 期间或之后两周内对抗 JCV 抗体水平的解释可能存在问题，但 PLEX 并未消除体液性 JCV 免疫，并且抗体水平迅速恢复。
