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dc.contributor.authorde Oliveira, G. L.V.
dc.contributor.authorFerreira, A. F.
dc.contributor.authorGasparotto, E. P.L.
dc.contributor.authorKashima, S.
dc.contributor.authorCovas, D. T.
dc.contributor.authorGuerreiro, C. T.
dc.contributor.authorBrum, D. G. [UNESP]
dc.contributor.authorBarreira, A. A.
dc.contributor.authorVoltarelli, J. C.
dc.contributor.authorSim�es, B. P.
dc.contributor.authorOliveira, M. C.
dc.contributor.authorde Castro, F. A.
dc.contributor.authorMalmegrim, K. C.R.
dc.identifier.citationClinical and Experimental Immunology, v. 187, n. 3, p. 383-398, 2017.
dc.description.abstractDefective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL, FAS, FASL, A1, BCL2, BCLXL, CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day�+�720 post-transplantation. Furthermore, in these patients, we observed increased CD8+ Fas+ T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day +�720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.en
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.relation.ispartofClinical and Experimental Immunology
dc.subjectapoptosis-related molecules
dc.subjectautologous haematopoietic stem cell transplantation
dc.subjectautoreactive cells
dc.subjectimmune tolerance
dc.subjectmultiple sclerosis
dc.titleDefective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantationen
dc.contributor.institutionFaculty of Pharmaceutical Sciences of Ribeir�o Preto
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.description.affiliationDepartment of Clinical Toxicological and Bromatological Analysis Faculty of Pharmaceutical Sciences of Ribeir�o Preto
dc.description.affiliationCenter for Cell-Based Research Regional Blood Center of Ribeir�o Preto School of Medicine of Ribeir�o Preto S�o Paulo Brazil University of S�o Paulo (USP)
dc.description.affiliationDepartment of Neurology Psicology and Psiquiatry School of Medicine of Botucatu University of State of S�o Paulo (UNESP)
dc.description.affiliationDepartment of Clinical Medicine School of Medicine of Ribeir�o Preto University of S�o Paulo (USP)
dc.description.affiliationUnespDepartment of Neurology Psicology and Psiquiatry School of Medicine of Botucatu University of State of S�o Paulo (UNESP)
dc.rights.accessRightsAcesso restrito
dc.description.sponsorshipIdFAPESP: 2008/57877-3
dc.description.sponsorshipIdFAPESP: 2008/58387
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