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Bonemarrow transplantation fails to halt intrathecal lymphocyte activation in MS
  1. T Mondria (tmondria{at}chello.nl)
  1. ErasmusMC, Netherlands
    1. C H.J. Lamers (c.lamers{at}erasmusmc.nl)
    1. ErasmusMC, Netherlands
      1. P A.W. te Boekhorst (p.teboekhorst{at}erasmusmc.nl)
      1. ErasmusMC, Netherlands
        1. J W Gratama (j.w.gratama{at}erasmusmc.nl)
        1. ErasmusMC, Netherlands
          1. R Q Hintzen (r.hintzen{at}erasmusmc.nl)
          1. ErasmusMC, Netherlands

            Abstract

            Background: Given the presumed key role for autoreactive lymphocytes in multiple sclerosis (MS), treatment strategies have been developed to ablate lymphocyte activity. Intrathecal lymphocyte activation can be measured by CSF-soluble(s)CD27.

            Objective: To determine the effect of maximum whole body immune ablation on two different markers that detect lymphocyte activation in CSF, oligoclonal IgG bands and levels of CSF-sCD27.

            Design, setting and patients: We quantified sCD27 levels and assessed the presence of oligoclonal IgG bands in CSF samples of secondary progressive MS patients treated by autologous bone marrow transplantation (BMT). In eight individuals, CSF was taken before and 6 to 9 months after conditioning. CSF-sCD27 levels were compared with other MS and non-inflammatory neurological disease (OND) controls. Regarding the effect of stem cell transplantation on CSF oligoclonal bands, we analyzed pooled data of this and 4 other international studies on stem cell transplantation in MS.

            Results: CSF-sCD27 was significantly lower after the extremely immunoablative protocol. However, levels remained elevated as compared with non-inflammatory controls and stayed within the range observed in other MS controls. The joint analysis of CSF oligoclonal bands demonstrated persistence of this immune abnormality in 88% of the reported cases (n=34).

            Conclusions: The persistence of CSF lymphocyte activation markers sCD27 and intrathecal oligoclonal IgG bands after maximum immunoablative treatment indicates that complete eradication of activated lymphocytes from the CNS has not been established. This is paralleled by disease progression observed in several studies on the effect of stem cell transplantation in MS.

            • Bone marrow transplantation
            • Cerebrospinal fluid
            • Multiple sclerosis
            • Neuro-immunology
            • sCD27

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