title: CD49d is a disease progression biomarker and a potential target for immunotherapy in Duchenne muscular dystrophy.
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(+)CD49d(hi) and CD8(+)CD49d(hi) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil ; Institute of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil ; Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617, Center for Research in Myology, 47 boulevard de l'Hopital, Paris, 75651 France.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Pinto-Mariz
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Rodrigues Carvalho
authors.affiliation: Institute of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Prufer De Queiroz Campos Araujo
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Wallace
authors.initials: W
authors.lastname: De Mello
authors.affiliation: Institute of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Márcia
authors.initials: M
authors.lastname: Gonçalves Ribeiro
authors.affiliation: Institute of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Maria Do Carmo Soares Alves
authors.initials: Mdo C
authors.lastname: Cunha
authors.affiliation: Service de Médecine Interne 1, Université Pierre et Marie Curie, Paris, France.
authors.forename: Pedro Hernan
authors.initials: PH
authors.lastname: Cabello
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Ingo
authors.initials: I
authors.lastname: Riederer
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617, Center for Research in Myology, 47 boulevard de l'Hopital, Paris, 75651 France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Negroni
authors.affiliation: INSERM U-E10, Necker Hospital, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Veras
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617, Center for Research in Myology, 47 boulevard de l'Hopital, Paris, 75651 France.
authors.forename: Erica
authors.initials: E
authors.lastname: Yada
authors.affiliation: Service de Médecine Interne 1, Université Pierre et Marie Curie, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allenbach
authors.affiliation: Service de Médecine Interne 1, Université Pierre et Marie Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Benveniste
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617, Center for Research in Myology, 47 boulevard de l'Hopital, Paris, 75651 France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617, Center for Research in Myology, 47 boulevard de l'Hopital, Paris, 75651 France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil ; Department of Clinical Research, National Cancer Institute (INCA), Rio de Janeiro, Brazil.
authors.forename: Suse Dayse
authors.initials: SD
authors.lastname: Silva-Barbosa
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, CNRS FRE3617, Center for Research in Myology, 47 boulevard de l'Hopital, Paris, 75651 France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
keywords: CD49d; Duchenne muscular dystrophy; Immunotherapy; Inflammation; Predictive biomarker; T lymphocytes