Research questions: Are there disease-specific biomarkers for autoimmune neuromuscular diseases?
Objectives: Integrative analysis of genetic and proteomics data to understand the genetic risk factors, corresponding changes in proteomics data, and alteration in immune environment in autoimmune neuromuscular diseases to potentially identify disease-specific biomarkers and improve patient care.
Scientific rationale: Autoimmune neuromuscular diseases are rare but can significantly interfere with patients’ quality of life (Bos et al., Disabil Rehabil, 2019). These autoimmune diseases affect the muscle (inflammatory myositis, dermatomyositis), neuromuscular junction (myasthenia gravis), or peripheral nerves (chronic inflammatory demyelinating neuropathy) and lead to weakness, paresthesia, fatigue, etc. There are scattered efforts to understand the autoimmune environment in these diseases but these studies often lack the power needed to understand this complex mechanism in depth. Moreover, these studies mostly compare the autoimmune environemtn against healthy control and comparison with non-autoimmune diseases affecting muscle and nerves are often lacking. While they are reasonable approaches to identify biomarkers, but no conclusion can be made whether the identified biomarker is specific to the disease or just reflects on the immune pathway active in that disease. For example, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-!B) pathway is impaired in many autoimmune diseases, and proteins related to this pathway can be potentially elevated in different autoimmune neuromuscular diseases, but such markers are not specific to a disease. An in-depth analysis of proteomics and genomics of these autoimmune and hereditary neuromuscular disorder and their epidemiolgical aspects, is critical to better understand the pathogenic differences, and to identify disease-specific biomarker that can tailor our therapeutic approach toward these diseases.
