G.P.168

• Published in: Neuromuscular disorders : NMD Vol. 24; no. 9; p. 856
• Main Authors: Preuße, C, Schara, U, Goebel, H.H, Zerbe, N, Hufnagl, P, Heppner, F.L, von Moers, A, Stenzel, W
• Format: Journal Article
• Language: English
• Published: 01.10.2014
• Subjects: Neurology
• DOI: 10.1016/j.nmd.2014.06.210
• ISSN: 0960-8966

As the most frequent genetic muscle disease worldwide, Duchenne Muscular Dystrophy affects ∼1:5 000 male births. Caused by a defective DMD gene, the dystrophin protein expression is severely hampered and the protein is only partially functional or completely dysfunctional. The constant breakdown of fibres leads to focal necrosis, myophagocytosis and a disease-stage dependent influx of inflammatory cells into the muscle tissue. A further hallmark of the disease is the development of endomysial fibrosis, whereby the amount of fibrosis directly correlates with an adverse outcome and early loss of ambulation. The molecular pathomechanisms underlying development and nature of fibrosis in DMD are not well understood. To study the link between inflammation and fibrosis we analysed macrophage and T cell immunology with regard to development of fibrosis at different time points and identified target molecules involved in this process. We have analysed muscle biopsies derived from DMD patients obtained at different time-points after onset of disease and studied the immune response at protein and mRNA level. Especially the polarisation of macrophages into pro-inflammatory, classically activated M1 phenotype and their switch to an alternatively activated (M2-‘repair phenotype’ during disease progression was investigated. We show a direct link between aaMph’s and fibrogenesis linked to a certain time frame in DMD. An automated whole slide image based quantification of fibrosis showed an increase of fibrosis over time, while the number of macrophages decreased. Polarisation of macrophages showed CD206 positivity. Comparison to patients suffering from Becker muscular dystrophy and female carriers of the defective DMD gene showed less development of fibrosis, and macrophages were only scant. Hopefully the results of this study may add to the development of a time-dependent immune intervention therapy, which can be ideally supplemental to other e.g. gene-therapeutic approaches.