title: Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation.
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 CD27(high) 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.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ligocki
authors.forename: W H
authors.initials: WH
authors.lastname: Rounds
authors.forename: E M
authors.initials: EM
authors.lastname: Cameron
authors.forename: C T
authors.initials: CT
authors.lastname: Harp
authors.forename: E M
authors.initials: EM
authors.lastname: Frohman
authors.forename: A M
authors.initials: AM
authors.lastname: Courtney
authors.forename: S
authors.initials: S
authors.lastname: Vernino
authors.forename: L G
authors.initials: LG
authors.lastname: Cowell
authors.forename: B
authors.initials: B
authors.lastname: Greenberg
authors.forename: N L
authors.initials: NL
authors.lastname: Monson
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009188:Myelitis, Transverse / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7