Pathogenic pathway discovery in inflammatory myopathy (2016)

Iago Pinal-Fernandez
National Institutes of Health
In recent years, many new drugs have been discovered that are effective in blocking specific substances that cause inflammation. Knowing which of these substances are involved in each autoimmune disease is key to finding the best treatment for each disorder. Myositis is an especially complex group of diseases, since different inflammatory substances are found in each of several distinct subsets of the disease. We intend to identify, compare, and validate the unique genetic patterns that may be causing disease in patients with different types of myositis. We expect to define specific groups of substances causing inflammation that can be targeted with treatment to improve each disease.

Signatures of microbial infection in myositis (2016)

Janine Lamb, BSc, DPhil
University of Manchester, UK
Myositis is thought to be caused by environmental triggers, such as viral infections, particularly in people with a particular genetic risk profile. Through our international myositis genetics collaboration, we have identified a genetic variation that potentially increases viral entry into cells of those with inclusion body myositis. Similarly, proteins found in people with dermatomyositis may reduce their ability to prevent viral infection. We will use a novel method, previously used in cancer research, to screen myositis patient groups to identify signatures of infection that are either unique or more common in one group than the other. This could help us to understand what causes different forms of idiopathic inflammatory myopathy so that we can more clearly define different types of myositis and select the most appropriate treatment.

Novel outcome measures in adult myositis using a physical activity monitor and the PROMIS physical function assessments (2015)

Rohit Aggarwal, MD, MS
University of Pittsburgh, Pittsburgh, PA
Patients often view their response to treatment differently than their doctor. In assessing new treatments for myositis through clinical trials, there is a need for better tools to assess the physical function before and after treatment. This pilot study evaluates data from physical activity monitors (such as FitBit or Apple Watch) as an objective outcome measure of physical function parameters, such as number of steps, flights of stairs, distance travelled, pattern of physical activity and total energy expenditure. These data are used in conjunction with the PROMIS (Patient Reported Outcomes Measurement Information System) physical function short form 20 (PF-20), which assesses outcome measures that are most important to patients. This study hopes to discover better measures of physical function in myositis patients based on objective physical activity measurements and on patient self-reported functional levels.

Characterization of skeletal muscle secretome involvement in the etiopathology of idiopathic inflammatory myopathy (2015)

Robert Cooper, MB/ChB
University of Liverpool, Liverpool, United Kingdom
The idiopathic inflammatory myopathies (IIM) are a group of rare connective tissue diseases, collectively termed myositis, that cause disproportionately severe disability due to chronic weakness. This is despite the use of a variety of powerful immunosuppressive agents. Muscle biopsy studies confirm that weakness can persist even when inflammatory cell infiltrates are suppressed, thus suggesting that other processes may contribute to weakness. Given data that suggests that muscle can act as a source of cytokines (particular proteins that play an important role in modulating the immune response), this study hypothesizes that these proteins may play an important contributing role in the severity of disease in IIM. This research aims to characterize the whole repertoire of proteins secreted by muscle in IIM in order to better understand the mechanism that results in underlying muscle weakness.

Lung as a site for break of tolerance and initiation of anti-Jo-1 positive myositis (2015)

Ingrid Lundberg, MD, PhD
Karolinska Institute, Stockholm, Sweden
Patients with myositis who have Jo-1 antibodies often have inflammation in the lung that can cause severe symptoms such as shortness of breath and cough. Lung symptoms often precede the muscle weakness characteristic of the disease. Working from the hypothesis that the autoimmune process may start in the lung and then spread to the muscles, this study more closely evaluates the role of inflammatory lung disease in the development of myositis in patients who have Jo-1 antibodies.

T follicular helper cells in human myositis (2015)

Timothy Niewold, MD
Mayo Clinic, Rochester, MN
This study investigates an immune cell that functions uniquely in human myositis, the follicular helper T cell (TFH). These cells facilitate immune responses by helping antibody-producing cells mature and develop. In myositis, these cells are present in greater numbers and correlate with disease activity. Working from the hypothesis that these cells are causing inflammation in myositis patients, this study examines TFH in both muscle biopsy samples and in the blood to determine their function in human myositis, both in adult and juvenile patients.

Predictive modeling of response to treatment of inflammatory myositis (2013)

Ann Reed, MD
Mayo Clinic, Rochester, MN
The ability to determine clinical improvement in idiopathic inflammatory myopathies (IIM) is routinely performed using muscle testing and measures of enzymes in the blood. These evaluations are limited, however, and improved methods for monitoring disease are needed. This study aims to develop a predictive model of clinical disease improvement based on evaluation of previously collected clinical and biological data in adult and pediatric dermatomyositis and adult polymyositis. The study analyzes the immune system data and autoantibody phenotype along with other clinical data to improve our ability to predict clinical improvement, disease outcome, and prognosis.

The quantitative and functional evaluation of lipoproteins in idiopathic inflammatory myopathies (2010)

Christina Charles-Schoeman, MD
University of California, Los Angeles, CA
This research investigated the function of HDL, the so-called “good cholesterol.” Investigators found that the function of HDL is abnormal in patients with inflammatory myositis and are investigating how it may contribute to disease and cardiovascular risk. This ongoing project has developed a research cohort at UCLA that is now following more than 200 patients.

Potential environmental triggers of myositis (2010)

Frederick W. Miller, MD, PhD
National Institute of Environmental Health Sciences, NIH
The Myositis in Military Personnel Study compared those who developed myositis with matched subjects who did not develop an autoimmune disease during active duty service to assess factors that might determine who gets the disease.

Environment-induced epigenetic changes in skeletal muscle and their role in myositis (2010)

Kanneboyina Nagaraju, DVM, PhD
Children’s National Medical Center
This study attempted to determine whether inflammation is solely responsible for muscle weakness or not. Based on this research, investigators found that inflammation is partly responsible for the weakness, but there are other factors that cause weakness in myositis, including environmental agents such as viruses, and statin drugs.

Mechanisms of muscle fiber damage and dysfunction in myositis (2003)

Kanneboyina Nagaraju, MD
Johns Hopkins Medical Center, Baltimore, MD
Like other autoimmune diseases, idiopathic inflammatory myopathies are treated with either glucocorticoids or immunosuppressive drugs. However, many patients with an IIM are frequently resistant to immunosuppressive treatments, and there is compelling evidence to indicate that several non-immune mechanisms play a causal role in these disorders. This research explored some of these non-immune mechanisms of muscle fiber damage.