Autoimmune neurologic diseases

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Clinical Significance of Intrathecal Baff/april Axis in Ms

Thursday, June 15
5:45 PM - 7:00 PM

B cell-activating factor (BAFF) and a proliferation-inducing ligands (APRIL) are TNF superfamily ligands involved in differentiation and maturation of peripheral B cells. Both ligands can promote survival of autoreactive B cell clones and have been associated with numerous autoimmune conditions. In fact, increased level of BAFF in blood has been previously reported during MS relapse; however, its clinical significance remains controversial. We have explored clinical features of relapsing-remitting MS patients, currently not on DMT, by focusing on the balance of CNS-produced BAFF/APRIL at the time of their clinical relapse. We have found that the ratio of BAFF CFS-to-serum index against that of APRIL (herein referred to as BAFF/APRIL index ratio) is indeed significantly elevated in patients with increased intrathecal IgG production and oligoclonal band (OCB) presence. Furthermore, BAFF/APRIL index ratio is positively correlated with CNS lesion numbers, but not with duration of the disease, nor severity of the attack, nor disease activity leading to the attack, as represented by EDSS and prior annual relapse rate (ARR). Interestingly, patients with higher BAFF/APRIL index ratio seem to experience more frequent relapses within the following year despite the treatment. Our study implies that patients with activated B cell status during their attack, via BAFF skewed signaling pathway in CNS, may experience difficulty in controlling disease activity. Although further study is required to determine whether our findings reflect a particular phase or a distinctive subtype of this disease, BAFF/APRIL index ratio may be an effective marker for patients benefitting from B cell-directed immunotherapy.

Akiko Takahashi

The University of Tokyo Hospital

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    Kaori Sakuishi

    Assistant Professor
    University of Tokyo Hospital

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      Jun Shimizu

      Associate Professor
      The University of Tokyo Hospital

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        Shoji Tsuji

        Professor
        The University of Tokyo Hospital

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