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Article

Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy

1
Department of Pharmaceutical Science, School of Pharmacy and Pharmaceutical Sciences, Binghamton University—SUNY, Johnson City, NY 13790, USA
2
Department of Biomedical Engineering, Binghamton University—SUNY, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA
3
Department of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, Canada
4
Center for Genetic Medicine Research, Children’s Research Institute, Children’s National Hospital, Washington, DC 20010, USA
*
Author to whom correspondence should be addressed.
Names and affiliations of the CINRG-DNHS Investigators are provided in the Acknowledgments.
Academic Editor: Gopal J. Babu
Life 2021, 11(8), 827; https://doi.org/10.3390/life11080827
Received: 22 July 2021 / Revised: 10 August 2021 / Accepted: 11 August 2021 / Published: 13 August 2021
(This article belongs to the Special Issue Duchenne Muscular Dystrophy: Mechanisms and Therapeutic Strategies)
Duchenne muscular dystrophy (DMD) is a progressive muscle disease involving complex skeletal muscle pathogenesis. The pathogenesis is triggered by sarcolemma instability due to the lack of dystrophin protein expression, leading to Ca2+ influx, muscle fiber apoptosis, inflammation, muscle necrosis, and fibrosis. Our lab recently used two high-throughput multiplexing techniques (e.g., SomaScan® aptamer assay and tandem mass tag-(TMT) approach) and identified a series of serum protein biomarkers tied to different pathobiochemical pathways. In this study, we focused on validating the circulating levels of three proinflammatory chemokines (CCL2, CXCL10, and CCL18) that are believed to be involved in an early stage of muscle pathogenesis. We used highly specific and reproducible MSD ELISA assays and examined the association of these chemokines with DMD pathogenesis, age, disease severity, and response to glucocorticoid treatment. As expected, we confirmed that these three chemokines were significantly elevated in serum and muscle samples of DMD patients relative to age-matched healthy controls (p-value < 0.05, CCL18 was not significantly altered in muscle samples). These three chemokines were not significantly elevated in Becker muscular dystrophy (BMD) patients, a milder form of dystrophinopathy, when compared in a one-way ANOVA to a control group but remained significantly elevated in the age-matched DMD group (p < 0.05). CCL2 and CCL18 but not CXCL10 declined with age in DMD patients, whereas all three chemokines remained unchanged with age in BMD and controls. Only CCL2 showed significant association with time to climb four steps in the DMD group (r = 0.48, p = 0.038) and neared significant association with patients’ reported outcome in the BMD group (r = 0.39, p = 0.058). Furthermore, CCL2 was found to be elevated in a serum of the mdx mouse model of DMD, relative to wild-type mouse model. This study suggests that CCL2 might be a suitable candidate biomarker for follow-up studies to demonstrate its physiological significance and clinical utility in DMD. View Full-Text
Keywords: Duchenne muscular dystrophy; Becker muscular dystrophy; disease severity; inflammatory biomarkers; chemokines; validation studies Duchenne muscular dystrophy; Becker muscular dystrophy; disease severity; inflammatory biomarkers; chemokines; validation studies
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MDPI and ACS Style

Ogundele, M.; Zhang, J.S.; Goswami, M.V.; Barbieri, M.L.; Dang, U.J.; Novak, J.S.; Hoffman, E.P.; Nagaraju, K.; CINRG-DNHS Investigators; Hathout, Y. Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy. Life 2021, 11, 827. https://doi.org/10.3390/life11080827

AMA Style

Ogundele M, Zhang JS, Goswami MV, Barbieri ML, Dang UJ, Novak JS, Hoffman EP, Nagaraju K, CINRG-DNHS Investigators, Hathout Y. Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy. Life. 2021; 11(8):827. https://doi.org/10.3390/life11080827

Chicago/Turabian Style

Ogundele, Michael, Jesslyn S. Zhang, Mansi V. Goswami, Marissa L. Barbieri, Utkarsh J. Dang, James S. Novak, Eric P. Hoffman, Kanneboyina Nagaraju, CINRG-DNHS Investigators, and Yetrib Hathout. 2021. "Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy" Life 11, no. 8: 827. https://doi.org/10.3390/life11080827

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