Other Names: Anti-Jo1 syndrome, AS syndrome

Antisynthetase syndrome is a chronic autoimmune disease that affects the muscles and other parts of the body. Signs and symptoms can vary but may include myositis, polyarthritis, interstitial lung disease, thickening and cracking of the hands, and Raynaud phenomenon.

 

Pathophysiology and Epidemiology

In antisynthetase syndrome, the production of aminoacyl-tRNA synthetases appears to be linked to the cause of the syndrome. These autoantibodies seem to appear after certain viral infections, drug exposure or in some people who already have a genetic predisposition. The exact role of autoantibodies in causing antisynthetase syndrome is not yet understood.

Aminoacyl-tRNA synthase (ARS) autoantibodies associated with antisynthetase syndrome include anti-Jo1 (anti-histidyl),  anti-EJ (anti-glycyl), anti-OJ (anti-isoleucyl), anti-PL7 (anti-threonyl), anti-PL12 (anti-alanyl), anti-SC (anti-lysil), anti-KS (anti-asparaginyl), anti-JS (anti-glutaminyl), anti-Ha or anti-YRS (anti-threonyl), anti-tryptophanyl, and anti-Zo (anti-phenylalanyl) autoantibodies. Anti-Jo1 is the most commonly associated with antisynthetase syndrome. 

 

Signs and Symptoms

Common symptoms of antisynthetase syndrome include:

  • Fever
  • Loss of appetite
  • Weight loss
  • Myositis
  • Polyarthritis
  • Interstitial lung disease causing shortness of breath, coughing, and/or dysphagia
  • Thickened skin of tips and margins of the fingers
  • Raynaud phenomenon

 

Diagnosis

Diagnosis is considered in patients with an antisynthetase antibody plus two major criteria or one major criterion and two minor criteria:

Major criteria:

  1. Interstitial lung disease (not explained by environmental, occupational, medication exposure, and not related to any other base disease)
  2. Polymyositis or dermatomyositis

Minor criteria:

  1. Arthritis
  2. Raynaud phenomenon
  3. Mechanic’s hand

Additional testing can then be ordered to confirm the diagnosis, determine the severity of the condition, and assist with determining treatment. This testing varies based on the signs and symptoms present in each person, but may include:

  • Blood tests to evaluate levels of muscle enzymes such as creatine kinase and aldolase
  • Laboratory tests to look for the presence of autoantibodies associated with antisynthetase syndrome
  • High resolution computed tomography (HRCT) of the lungs
  • Electromyography (EMG)
  • Muscle biopsy
  • Pulmonary function testing
  • Magnetic resonance imaging (MRI) of affected muscles
  • Evaluation of swallowing difficulties and aspiration risk
  • Lung biopsy

 

Management and Current Treatment

Corticosteroids are typically the first-line of treatment for antisynthetase syndrome and may be required for several months or years. These medications are often given orally; however, in severe cases, intravenous methylprednisolone may be initially prescribed. Immunosuppressive medications may also be recommended, especially in people with severe muscle weakness or symptomatic interstitial lung disease. Physical therapy may also be necessary to improve weakness, reduce further muscle wasting from disuse, and prevent muscle contractures.

 

Clinical Trial Information

For a full list of clinical trials relating to antisynthetase syndrome, go here.

 

Resources

The Myositis Foundation 

Myositis Support & Understanding

Antisynthetase Syndrome – NORD

Antisynthetase Syndrome – NIH