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Updated: Mar 28, 2026
Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy
Published on: January 12, 2019
CD49d is a disease progression biomarker and a potential target for immunotherapy in Duchenne muscular dystrophy
Fernanda Pinto-Mariz1, Luciana Rodrigues Carvalho2, Alexandra Prufer De Queiroz Campos Araujo3
1Laboratory 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.
Insights
Increased CD49d T cells indicate Duchenne muscular dystrophy (DMD) severity and progression. Targeting CD49d may offer a therapeutic strategy for DMD patients, reducing inflammation and tissue damage.
Area of Science:
- Immunology
- Genetics
- Neurology
Background:
- Duchenne muscular dystrophy (DMD) is a genetic disorder caused by dystrophin gene mutations.
- Immune inflammatory responses exacerbate DMD progression.
- Previous studies identified elevated CD49dhi and CD49ehi T cells in DMD patients.
Purpose of the Study:
- To identify reliable noninvasive biomarkers for DMD progression.
- To correlate T cell subsets with disease severity and progression in DMD.
- To explore the therapeutic potential of targeting CD49d in DMD.
Main Methods:
- Analysis of 75 DMD patients at various disease stages.
- Quantification of circulating CD4(+)CD49d(hi) and CD8(+)CD49d(hi) T lymphocytes.
- Assessment of T cell adhesion and migration, including transendothelial and fibronectin-driven responses.
- In vitro blocking studies using anti-CD49d monoclonal antibodies.
Main Results:
- Elevated percentages of CD4(+)CD49d(hi) and CD8(+)CD49d(hi) T cells correlated with DMD severity and rapid progression.
- CD49d-expressing T cells were present in muscle inflammatory infiltrates.
- T cells from severe DMD patients showed increased adhesion to myotubes and enhanced migratory responses.
- Anti-CD49d antibody treatment blocked these T cell functions.
Conclusions:
- CD49d serves as a novel biomarker for stratifying DMD patients and predicting disease progression in clinical trials.
- Anti-CD49d therapies (peptides or antibodies) show potential for reducing inflammation-mediated tissue damage in DMD.
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.
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.
