Growth differentiation factor-15 as an emerging biomarker for identifying myositis

ABSTRACT

Introduction

The autoimmune disorders of the skeletal muscle tissue termed myositis are a rare yet diverse group of diseases with distinct clinical and pathological features and with different prognoses and treatment responses. Subtyping of patients is necessary for appropriate disease management, and requires specialized expertise and elaborate diagnostic testing of clinico-pathological disease features.

Areas covered

Current clinical practice and diagnostic criteria for subtyping patients are searched on medical online platforms including PubMed and Web of Science. Recent publications on growth differentiation factor-15 (GDF-15) and muscle disorders are summarized and analyzed, and comparisons are made of data published in studies describing disease cohorts as well as individual patients. Influence of age and physical activity on GFD-15 levels and potential as a diagnostic criterion are discussed. This review contains supportive evidence of the elevated levels of GDF-15 in the blood of myositis patients, a feature which distinguishes these autoimmune muscle disorders from muscular dystrophy with secondary inflammation.

Expert opinion

GDF-15 represents a novel and promising serological biomarker for diagnosing myositis, yet more studies are needed to assay its sensitivity and specificity. Increased diagnostic power is expected by combining GDF-15 levels with other blood-derived biomarkers.

KEYWORDS:

• Anti-synthetase syndrome
• dermatomyositis
• growth differentiation factor-15
• immune-mediated necrotizing myopathy
• myositis
• polymyositis
• serological biomarkers
• sporadic inclusion body myositis

Article highlights

• Circulating GDF-15 levels show promise as a convenient diagnostic biomarker for myositis able to differentiate these diseases from other muscle disorders.

• GDF-15 is a multipurpose biomarker applicable also for other disorders, yet may require carefully matched controls as levels of this stress-related cytokine are influenced by age and physical activity.

• Assays quantifying GDF-15 can conveniently be combined with other established serological diagnostic markers for myositis, such as muscle enzymes and autoantibodies.

• Further development of a diagnostic workup containing multiple blood biomarkers, including GDF-15 and other key cytokines, could help avoid an invasive diagnostic muscle biopsy for a definite diagnosis of myositis subtypes.

• Possible use of GDF-15 as a biomarker for prognosis or to predict therapeutic response remains undocumented.

Acknowledgments

The author’s research is supported by private donations to the Fund for Research into Neuromuscular Diseases UGent GE461. Discussion on the influence of age and physical activity on GDF-15 levels in health and muscle disease and comparison between myositis and muscular dystrophies benefitted from data made available in published articles, publication supplements, and detailed datasets communicated by the authors, for which they deserve the sincerest gratitude. Thanks especially to S Yatsuga from Kurume University Japan, A Penas from Hospital 12 de Octubre Research Institute Madrid Spain, P Tsygankova from the Research Center for Medical Genetics Moscow Russia, M Conte from Bologna University Italy, and N Scharff Poulsen from Copenhagen Neuromuscular Center Denmark.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.