title: Detection of skewed T-cell receptor V-beta gene usage in the peripheral blood of patients with multiple sclerosis.
abstract: The ex vivo analysis of the T-cell receptor V-beta (TCRBV) gene usage by circulating T lymphocytes in Multiple Sclerosis (MS) patients may contribute to understanding disease pathogenesis. In the present study, TCRBV gene usage was analyzed in freshly collected unstimulated peripheral blood mononuclear cells (PBMC) isolated from 40 MS patients and 20 healthy controls. Nine patients presented abnormal repertoires, with expansion of one or more TCRBV segments. Among these patients, six presented expansion of TCRBV9 chain expression, three also having an expansion of TCRBV1, TCRBV11 and TCRBV22 segments. The most frequently observed TCRBV chain expansion, TCRBV9, was further analyzed and identified as polyclonal. Evaluation of clinical variables showed that median disease duration was shorter in patients with TCRBV gene expression abnormalities. Longitudinal evaluation of five patients with a skewed repertoire showed regression of expanded TCRBV chains expression to normal values. These data indicate that certain MS patients have abnormal TCRBV gene expression. Such abnormalities are caused by polyclonal expansions of T lymphocyte subpopulations that use the same TCRBV gene families, are unstable and preferentially observed early in the course of the disease.
authors.affiliation: Dept. of Neurological and Psychiatrical Sciences, University of Florence, Italy. bgran@box-b.nih.gov
authors.forename: B
authors.initials: B
authors.lastname: Gran
authors.forename: D
authors.initials: D
authors.lastname: Gestri
authors.forename: A
authors.initials: A
authors.lastname: Sottini
authors.forename: E
authors.initials: E
authors.lastname: Quiròs Roldàn
authors.forename: A
authors.initials: A
authors.lastname: Bettinardi
authors.forename: S
authors.initials: S
authors.lastname: Signorini
authors.forename: D
authors.initials: D
authors.lastname: Primi
authors.forename: C
authors.initials: C
authors.lastname: Ballerini
authors.forename: R
authors.initials: R
authors.lastname: Taiuti
authors.forename: L
authors.initials: L
authors.lastname: Amaducci
authors.forename: L
authors.initials: L
authors.lastname: Massacesi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007125:Immunogenetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D009103:Multiple Sclerosis / Q000097:blood* / Q000235:genetics*; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012016:Reference Values
chemical_list: D009692:Nucleic Acid Heteroduplexes; D016693:Receptors, Antigen, T-Cell, alpha-beta