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Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation

Genes & Immunity volume 14, pages 291–301 (2013)Cite this article

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Abstract

Patients with the autoimmune disease multiple sclerosis (MS) typically present with the clinically isolated syndromes (CIS) transverse myelitis (TM) or optic neuritis (ON). B-cell disturbances have been well documented in patients with MS and CIS patients with ON, but not in CIS patients with TM, despite the fact that these patients have the worst clinical outcome of all CIS types. The goal of this study was to characterize the B-cell populations and immunoglobulin genetics in TM patients. We found a unique expansion of CD27high plasmablasts in both the cerebrospinal fluid and periphery of TM patients that is not present in ON patients. Additionally, plasmablasts from TM patients show evidence for positive selection with increased somatic hypermutation accumulation in VH4+ B cells and receptor editing that is not observed in ON patients. These characteristics unique to TM patients may impact disease severity and progression.

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Acknowledgements

We thank the patients who consented to sampling for this study. Bonnie Darnell, Angie Mobley, Julia McClouth, Ann-Marie Schaefer and Elizabeth Curry are thanked for their technical expertise in cell sorting. This study was supported by Grants from the National Multiple Sclerosis Society (NMSS) to NLM (RG3267 and RG4653). AJL, WHR, EMC and CTH were supported by Grant no. NIH NRSA5 T32 AI 005284-28 from NIAID. LGC’s contributions were funded by Grant no. 1R01AI097403-01.

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  1. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    A J Ligocki, W H Rounds, E M Cameron, C T Harp, E M Frohman, A M Courtney, S Vernino, B Greenberg & N L Monson

  2. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA

    L G Cowell

  3. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    N L Monson

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  1. A J Ligocki
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Correspondence to N L Monson.

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Competing interests

EMF has received speaker and consulting fees from TEVA, Biogen Idec, Acorda and Novartis. EMF has received consulting fees from Abbott Laboratories and Genzyme. BG received honoraria from the MSAA and the AAN and has received consulting fees from Biogen Idec, Acorda Therapeutics, Sanofi-Aventis and DioGenix. BG has equity shares in DioGenix. NLM receives funding from MedImmune, Inc., TEVA Neuroscience, DioGenix, Inc. and the National MS Society. NLM is an advisor for Genentech, Inc. All the other authors declare no conflict of interest.

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Ligocki, A., Rounds, W., Cameron, E. et al. Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation. Genes Immun 14, 291–301 (2013). https://doi.org/10.1038/gene.2013.18

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