Current biomarkers in inclusion body myositis

Abstract

Inclusion body myositis (IBM) is an idiopathic muscle disorder primarily affecting adults above the age of 50. IBM is characterized by weakness in the knee extensor and deep finger flexor muscles due to muscle atrophy and fibroadipose replacement. Dynamometry and manual muscle testing are commonly used to assess patient muscle strength, while magnetic resonance imaging and electromyography studies identify the patterns of muscle atrophy and motor unit potentials. Although the underlying pathophysiological mechanisms of IBM are still unknown, common histopathological markers include rimmed vacuoles and inclusions. The immune system is also largely implicated in pathogenesis, as skeletal muscle in IBM overexpresses major histocompatibility complex I (MHC-I), and cluster of differentiation (CD) 8+ T-cells, and features endomysial inflammation. Antibodies to the cytosolic 5'-nucleotidase 1A (cN1A) protein have been associated with IBM but have low sensitivity and specificity. As many classic features of IBM present only in advanced stages of disease, there are substantial challenges to the diagnosis and monitoring of IBM progression in its early stages. Identifying early diagnostic biomarkers and new biomarker signatures associated with IBM disease progression is necessary for clinical trial readiness.

Keywords: biomarker discovery; electrodiagnostics; histopathology; imaging; immunology; inclusion body myositis; inflammatory muscle disorders; serology.