Antibodies are proteins that are part of the body’s natural immune system. They help the body recognize and remove foreign material, especially bacteria and viruses that can cause infection and disease.
In some cases, however, the immune system turns this protective function against the body’s own tissues. Rather than recognizing and fighting off foreign proteins, as antibodies usually do, autoantibodies recognize a person’s own proteins and start to attack them as if they were invaders. In the case of myositis, autoantibodies are directed against skeletal muscle. This is why myositis is called an autoimmune disease.
It is not clear why autoantibodies appear in the blood when a person has an autoimmune disease. They may appear years before clinical symptoms of the disease appear, they are not the cause of disease, and they do not usually have a functional role in the disease. Scientists use these proteins as biomarkers, a measurable factor that indicates the presence of a disease or other process.
The value of recognizing autoantibodies as biomarkers is that there is usually a close association between particular autoantibodies and a particular form of disease or set of clinical symptoms. An autoantibody can identify a subgroup of patients who have a similar prognosis and will respond similarly to a particular treatment. Autoantibody levels in the blood can also reflect disease activity, so they can help doctors tell how well a treatment is working.
Researchers continue to identify particular autoantibodies as biomarkers for myositis diseases. Among these are what are known as myositis-specific autoantibodies (MSA). These autoantibodies are rarely found in other diseases, so their presence in the patient’s blood can confirm the diagnosis of dermatomyositis, polymyositis, necrotizing myopathy, or sporadic inclusion body myositis. Children are less likely to have myositis-specific autoantibodies.
Myositis-specific antibodies have also improved our understanding of myositis by leading to the identification of certain clinical patterns that help doctors understand how the disease might progress.
Other autoantibodies, known as myositis-associated autoantibodies (MAA), have also been identified. These autoantibodies are found in patients with myositis, but they are also present in patients with other autoimmune diseases such as scleroderma. While still helpful in terms of treatment and disease course, this means myositis-associated autoantibodies cannot be used to definitively diagnose a patient with a specific myositis disease.
Antibody testing and predicted outcomes
It is recommended that all patients with myositis be tested for myositis-specific and -associated autoantibodies. Several commercial laboratories are now able to screen for a whole panel of autoantibodies with a single blood sample.
Generally, a patient will be positive for only one autoantibody. If an autoantibody is found, it is usually not necessary to test again to look for additional autoantibodies.
This chart shows the current myositis-specific autoantibodies and the clinical features they are associated with. Be sure the panel your doctor orders includes all of these MSAs.
Some of the most significant autoantibodies and their relevance to myositis include:
- Antisynthetase autoantibodies are a collection of antibodies that target tRNA synthetase enzymes. They are associated with antisynthetase syndrome. The most common antisynthetase antibody is anti-Jo-1. Others of significance include anti-PL-7 and anti-PL-12. Others occur less frequently and are of less significance, including anti-EJ, anti-OJ, anti-KS, anti-Zo, and anti-Ha.
- Anti-signal recognition particle (SRP) is associated with necrotizing myopathy (NM). Patients have a severe, sudden-onset of muscle weakness and muscle aches, and they may have cardiac involvement. This antibody may also be found in children who can have slowly increasing muscle weakness mimicking a muscular dystrophy.
- Anti-TIF1-γ antibody (human transcriptional intermediary factor) is the most common autoantibody found in children with juvenile dermatomyositis. It is also found in adults with dermatomyositis, and high levels of the antibody are associated with an increased risk of cancer-associated DM in adults.
- Anti-NXP2 (nuclear matrix protein 2) antibodies may be found in children and in adults and are associated with an increased risk of cancer. The presence of anti-NXP2 autoantibodies substantially increases the risk of calcinosis.
- Anti-SAE (anti-small ubiquitin like modifier activating enzyme heterodimer) autoantibodies are also associated with an increased risk of cancer in adults with dermatomyositis.
- IFN-induced melanoma differentiation-associated protein 5 (MDA5) is specific for DM and is associated with a clinical subset of the disease that includes skin manifestations without muscle involvement. It also involves rapidly progressive ILD both in children and adults.
- Anti-PM/Scl is associated with lung problems and an overlap of polymyositis and scleroderma. Children with PM-scleroderma overlap tend to have a strongly positive antinuclear antibody (ANA).
- HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) is a key enzyme in the production of cholesterol. Patients who have anti-HMGCR antibodies and use statin medications to control high cholesterol may develop statin-induced necrotizing myopathy. Those who know they have this antibody should never take statins. Nevertheless, some patients develop necrotizing myopathy, even though they never took statins.
- Anti-Ro/SSA antibody is the most prevalent MAA in myositis and frequently occurs together with anti-ARS antibodies or other MAAs.
What Your Antibodies Tell Your Doctor About Your Disease – Dr. Neil McHugh at the 2015 TMA Annual Patient Conference