Polymyositis

Definitions & Key takeaways

Polymyositis is an inflammatory disorder of the muscles, caused mainly by cytotoxic T- cells destroying muscle tissue due to molecular mimicry and resulting in bilateral proximal muscle weakness of large muscle groups. It is characterized by muscle weakness, muscle pain, and difficulty with activities of daily living. Its diagnosis involves elevated serum creatinine kinase and myositis- specific antibodies, and it is treated with corticosteroids and specialized physical exercise.

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Introduction0:00–0:24

In polymyositis, “myos-“ refers to the muscles, “poly-“ means many, and “-itis” refers to inflammation, so polymyositis is an inflammatory disorder which involves many muscle groups around the body.
Polymyositis is an immune- mediated disease, meaning that the immune system attacks the muscles in our own body. Normally, the cells of the immune system are ready to spot and destroy anything foreign that could cause the body harm.

Physiology0:24–2:27

To help with this, most cells in the body have a set of proteins that combine together to form something called a major histocompatibility complex, or MHC, class I molecule that sits on the surface of their cell membrane.
These surface proteins act kind of like a serving platter, presenting molecules from within the cell for the immune system to continually sample.
Normally though the molecule’s just a sample from the cell, and the immune system recognizes it as harmless, and this is known as a self-antigen, and there’s no response.
But when a cell is actually invaded by a pathogen like a virus, viral antigens are presented on the MHC class I molecule, and that sparks a different immune response.
A type of T-lymphocyte, called a CD8+ T-cell, also known as a cytotoxic T-cell, uses its T-cell receptors to bind to the antigen presented by the MHC class I molecule.
If the cytotoxic T-cell binds strongly, than the antigen is recognized as foreign, and the cytotoxic T-cell secretes a whole lot of perforin and granzymes.
Perforin forms big holes in the infected cell and that allows the granzymes to enter the cell. Once inside, the granzymes induce apoptosis, or programmed cell death.
As if that weren’t enough, the cytotoxic T-cells have a protein called Fas ligand on their surface, and it binds to a molecule called Fas on the surface of the infected cell.
When these two combine, it triggers a cascade of signaling events inside the target cell that also leads to apoptosis. Meanwhile, B- lymphocytes that react to the pathogen, can also start producing a whole lot of antibodies.
These antibodies bind the pathogen, and typically prevent it from attacking the host’s cells and, at the same time, “tag” the pathogen for further destruction by other immune cells.

Pathology2:27–4:11

In polymyositis, healthy muscle cells present normal muscle proteins on the MHC class I molecule, and the cytotoxic T-cells inappropriately react and get activated.
That’s because it’s thought that the muscle proteins might look similar to a foreign pathogen. This is called molecular mimicry, because from the perspective of the cytotoxic T-cell, a host protein is mimicking a foreign protein.
When our own proteins triggers an immune response, that protein is called an autoantigen. So when the cytotoxic T-cells are activated by the autoantigen, they cause apoptosis of the muscle cells.
In some cases, B-cells start producing antibodies against these autoantigens as well. The specific antigenic targets in polymyositis include tRNA synthetases, also called Jo-1, a nuclear protein, known as Mi-2, and components of the signal-recognition particle, or SRP for short, which helps with proteins trafficking within the cell.
The immune reaction causes inflammation in and around the muscles that are being attacked by the immune response, and typically these attacks occur repeatedly over time and can involve different muscle groups.
The destruction of muscle cells can lead to muscle weakness and can cause muscle enzymes like aldolase and creatine kinase to spill into the blood.
Because it’s an autoimmune process, it’s also possible for polymyositis to occur alongside other autoimmune connective-tissue diseases, including Sjogren’s syndrome, rheumatoid arthritis, or scleroderma.

Symptoms4:11–4:46

Symptoms of polymyositis usually include bilateral weakness and muscle wasting that mostly affects proximal, big muscle groups, like the shoulder or hips and usually spares the distal muscles like muscles in the hands.
Individuals might have difficulty rising from a chair, lifting their arms, climbing stairs, or combing their hair. Sometimes, these muscles may be tender or painful.
In severe cases, the muscles of the pharynx or the esophagus are involved, causing dysphagia or difficulty in swallowing.

Diagnosis4:46–5:14

Diagnosis is based on identifying myositis- specific antibodies, like anti-Jo-1, as well as elevated serum levels of muscle enzymes such as aldolase or creatine kinase.
Additionally, electromyography can be used to detect regions of dead muscle cells that cause abnormal electrical signals conduction.
A muscle biopsy can show inflammation and varying stages of necrosis. Treatment of polymyositis typically focuses on suppressing the immune response, usually with corticosteroids.

Treatment5:14–5:27

In addition, specialized exercise therapy can help maintain muscle function. All right, as a quick recap, polymyositis is an inflammatory disorder of the muscles, caused mainly by cytotoxic T- cells destroying muscle tissue due to molecular mimicry and resulting in bilateral proximal muscle weakness of large muscle groups.

Review5:27–5:51

Its diagnosis involves elevated serum creatinine kinase and anti-Jo-1 antibodies and it is treated with corticosteroids.