The effect of plasma exchange on serum anti-JC virus antibodies

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.