Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/13053
Title: CD49d is a disease progression biomarker and a potential target for immunotherapy in Duchenne muscular dystrophy
Authors: Mariz, Fernanda Pinto
Carvalho, Luciana Rodrigues
Araujo, Alexandra Prufer De Queiroz Campos
Mello, Wallace De
Ribeiro, Márcia Gonçalves
Cunha, Maria Do Carmo Soares Alves
Cabello, Pedro Hernan
Riederer, Ingo
Negroni, Elisa
Desguerre, Isabelle
Veras, Mariana
Yada, Erica
Allenbach, Yves
Benveniste, Olivier
Voit, Thomas
Mouly, Vincent
Barbosa, Suse Dayse Silva
Butler-Browne, Gillian
Savino, Wilson
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Pediatria. Rio de Janeiro, RJ, Brasil / Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617, Center for Research in Myology, 47 boulevard de l’Hopital, Paris 75651, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Pediatria. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Pediatria. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Pediatria. Rio de Janeiro, RJ, Brasil.
Université Pierre et Marie Curie. Service de Médecine Interne. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617. Center for Research in Myology, 47 boulevard de l’Hopital. Paris 75651, France
INSERM U-E10.Necker Hospital. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617. Center for Research in Myology, 47 boulevard de l’Hopital. Paris 75651, France
Université Pierre et Marie Curie. Service de Médecine Interne. Paris, France.
Université Pierre et Marie Curie. Service de Médecine Interne. Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617. Center for Research in Myology, 47 boulevard de l’Hopital. Paris 75651, France
Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617. Center for Research in Myology, 47 boulevard de l’Hopital. Paris 75651, France
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Câncer (INCA). Departamento de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil.
Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617. Center for Research in Myology, 47 boulevard de l’Hopital. Paris 75651, France
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Abstract: Background Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. The immune inflammatory response also contributes to disease progression in DMD patients. In a previous study, we demonstrated higher levels of circulating CD49dhi and CD49ehi T cells in DMD patients compared to healthy control. DMD patients are clinically heterogeneous and the functional defect cannot be correlated with genotype. Therefore, it is important to be able to define reliable noninvasive biomarkers to better define the disease progression at the beginning of clinical trials. Results We studied 75 DMD patients at different stages of their disease and observed that increased percentages of circulating CD4+CD49dhi and CD8+CD49dhi T lymphocytes were correlated with both severity and a more rapid progression of the disease. Moreover, T+CD49d+ cells were also found in muscular inflammatory infiltrates. Functionally, T cells from severely affected patients exhibited higher transendothelial and fibronectin-driven migratory responses and increased adhesion to myotubes, when compared to control individuals. These responses could be blocked with an anti-CD49d monoclonal antibody. Conclusion CD49d can be used as a novel biomarker to stratify DMD patients by predicting disease progression for clinical trials. Moreover, anti-CD49d peptides or antibodies can be used as a therapeutic approach to decrease inflammation-mediated tissue damage in DMD.
Keywords: Duchenne muscular dystrophy
Inflammation
CD49d
T lymphocytes
Predictive biomarker
Immunotherapy
keywords: Biomarcador preditivo
DeCS: Distrofia Muscular de Duchenne
Inflamação
Linfócitos T
Imunoterapia
Issue Date: 2015
Publisher: BioMed Central
Citation: MARIZ, Fernanda Pinto; et al. CD49d is a disease progression biomarker and a potential target for immunotherapy in Duchenne muscular dystrophy. Skeletal Muscle, v.5:45, 10p, Dec. 2015.
DOI: 10.1186/s13395-015-0066-2
ISSN: 2044-5040
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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