title: Serial blood T cell repertoire alterations in multiple sclerosis patients; correlation with clinical and MRI parameters.
abstract: A significant skewing of the peripheral T cell repertoire has been shown in relapsing-remitting multiple sclerosis (MS). Most of the studies already performed in this field are cross-sectional and therefore, little is known of the T cell repertoire evolution over time in MS and the correlation of T cell repertoire variation with clinical and MRI parameters. This study was performed on serially harvested frozen PBMC from nine untreated MS patients (27 samples) and 14 healthy individuals. The blood T cell repertoire of each patient was analysed at the complementarity determining region 3 (CDR3) level and compared with a monthly MRI scan performed over a six month period with assessment of T2 lesion load and gadolinium enhancing lesions. A highly significant blood T cell repertoire skewing was observed in MS patients as compared with healthy controls (p<0.01). In addition, the number of altered Vbeta families correlated significantly with both the T2 lesion volume and the number of gadolinium enhancing lesions as assessed by MRI (Spearman correlation tests, r=0.51 and r=0.44, p<0.01 and p<0.05 respectively). Furthermore, the variation of the number of altered Vbeta families over time also correlated with the appearance of new gadolinium enhancing lesions (r=0.36, p=0.05). These findings which need confirmation on larger serial cohorts, suggest an association between the magnitude of TCRBV CDR3 length distribution alterations in the peripheral blood of MS patients and the disease process.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale Unité 643: Immunointervention dans les allo- et Xénotransplantations, Institut de Transplantation Et de Recherche en Transplantation CHU Hôtel Dieu, 30 Bd Jean Monnet, 44093 Nantes Cedex, France.
authors.forename: David-Axel
authors.initials: DA
authors.lastname: Laplaud
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.forename: Patrick
authors.initials: P
authors.lastname: Miqueu
authors.forename: Kasia
authors.initials: K
authors.lastname: Bourcier
authors.forename: Julien
authors.initials: J
authors.lastname: Moynard
authors.forename: Yannick
authors.initials: Y
authors.lastname: Oudinet
authors.forename: Marina
authors.initials: M
authors.lastname: Guillet
authors.forename: Catherine
authors.initials: C
authors.lastname: Ruiz
authors.forename: Neal
authors.initials: N
authors.lastname: Oden
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.forename: Charles R G
authors.initials: CR
authors.lastname: Guttmann
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000276:immunology / Q000503:physiopathology; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D022801:Complementarity Determining Regions / Q000032:analysis / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007159:Immunologic Tests; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D011237:Predictive Value of Tests; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013223:Statistics as Topic; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell