Author response: Intrathecal IgM production is a strong risk factor for early conversion to multiple sclerosis

We thank Alcalá et al. for their very pertinent comments to our article.1 Although their group used a qualitative method—intrathecal oligoclonal immunoglobulin [Ig]M bands2—and our work applied a quantitative approach—calculation of the fraction of intrathecally produced IgM—for detection of an intrathecal IgM production, their and our work consistently show that the presence of an intrathecal IgM production in patients with a clinically isolated syndrome is clearly associated with an increased risk of conversion to multiple sclerosis (MS). Of note, this conclusion is likewise reached by a recent comprehensive literature review that summarized a total of 12 prospective and retrospective studies addressing this issue.3 However, the key questions of why a certain proportion of patients with MS has an intrathecal production of IgM and whether these patients differ pathogenically from those without an intrathecal IgM production currently remain unanswered. Although further research will be required to clarify these points, it definitely seems highly interesting and warranted to closely evaluate the effectiveness of immunotherapies for MS according to the presence/absence of an intrathecal IgM production, with the aim of developing individualized treatment strategies for patients with early MS.

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