RESUMO
Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.
Assuntos
Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/imunologia , Estudos de Casos e Controles , Análise por Conglomerados , Regulação da Expressão Gênica , Heterogeneidade Genética , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Esclerose Múltipla Recidivante-Remitente/sangue , Análise de Sequência com Séries de Oligonucleotídeos , Infecções por Poxviridae/genética , Transdução de Sinais , Regulação para CimaRESUMO
We present a measurement of the left-right cross-section asymmetry ( A(LR)) for Z boson production by e(+)e(-) collisions. The measurement includes the final data taken with the SLD detector at the SLAC Linear Collider during the period 1996-1998. Using a sample of 383 487 Z decays collected during the 1996-1998 runs we measure the pole value of the asymmetry, A(0)(LR), to be 0.150 56+/-0.002 39 which is equivalent to an effective weak mixing angle of sin (2)straight theta(eff)(W) = 0.231 07+/-0.000 30. Our result for the complete 1992-1998 data set comprising approximately 537 000 Z decays is sin (2)straight theta(eff)(W) = 0.230 97+/-0.000 27.