Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder causing progressive weakness of facial, shoulder, and upper arm muscles. Its key driver is DUX4 gene misexpression, leading to inflammation, oxidative stress, and impaired muscle regeneration.
This thesis systematically examined immune mechanisms at both systemic and local levels.
Chapter 2 reviews FSHD’s genetic and epigenetic underpinnings, highlighting DUX4-induced immune dysregulation and therapeutic strategies.
Chapter 3 found no evidence of autoantibody involvement, shifting focus to innate immunity.
Chapter 4 identified elevated IL-6 and TNF, correlating with disease severity and linked to NK cell activation.
Chapter 5 uncovered CASP-8, 4EBP1, and SIRT2 as key inflammatory markers influencing IL-6 production.
Chapter 6 showed PAX7 gene repression correlates with disease severity, leading to the development of a non-invasive blood biomarker.
Chapter 7 revealed mitochondrial dysfunction, FAP expansion, and splicing anomalies, pointing to novel disease pathways.
Chapter 8 confirmed that TIRM+ muscles exhibit more severe inflammation and structural damage, validating TIRM MRI as a marker of active disease.
Together, these findings support a model where innate immunity and inflammation play central roles in FSHD progression and highlight targets for future therapies.