What is Extractable Nuclear Antigen (ENA) Antibodies panel? 

An ENA panel analyses your blood for the presence of autoantibodies that react with any of the six proteins present inside the nucleus of the cell (an organelle present in cell). These proteins include ribonucleoprotein (RNP), Smith (Sm), SSA, SSB, Scl-70 and Jo-1. Together, they are called “extractable” because they can be separated from the nucleus using saline (a mixture of salt and salt).

Antibodies are special proteins that your immune system makes to fight against harmful microbes and other harmful substances (called antigens). In an autoimmune disorder, the immune system malfunctions and produces antibodies that attack body’s own tissues, causing inflammation and tissue damage. These antibodies are called autoantibodies.

The presence of one or more ENA indicates the presence of specific autoimmune disorders. 

The ENA panel looks for the following:

  • Anti-RNP antibodies: These antibodies are produced against ribonucleoproteins (RNP) - a complex between RNA and proteins. RNA is a messenger molecule that transfers the information from your DNA outside the nucleus. It is observed in people with autoimmune disorders like systemic lupus erythematosus (SLE), mixed connective tissue disease and progressive systemic sclerosis. Anti-RNP antibodies are found alone in mixed connective tissue disease and along with anti-Sm antibodies in SLE.
  • Anti-Sm antibodies: This antibody is produced against Sm protein or smith antigen. It is almost only seen in people with SLE but is not present in all people with the disease. Anti-Sm antibody is found in about 20% of people with lupus and in less than 1% of healthy people. Since it is rarely found in people with other autoimmune disorders, anti-Sm antibodies test is used to confirm the diagnosis of SLE.
  • Anti-SSA and anti-SSB antibodies: These antibodies are used to diagnose an autoimmune disease called Sjögren syndrome. If Sjögren syndrome occurs alone, it is known as primary Sjögren syndrome, and if it occurs with other autoimmune conditions, it is known as secondary Sjögren syndrome. Sjögren syndrome can be diagnosed when both anti-SSA and anti-SSB antibodies are present. Although both antibodies are seen in more than 50% of people with primary Sjögren syndrome, they are only found occasionally in secondary Sjögren syndrome associated with rheumatoid arthritis. In fact, anti-SSB antibodies are only seen in primary Sjögren syndrome. Thus, these antibodies are also helpful in distinguishing between primary and secondary Sjögren syndrome. Additionally, anti-SSA antibodies are found in about 25% of people with SLE.
  • Scl-70 antibody: Scl-70 antibody is also known as topoisomerase 1 antibodies since they are formed against the enzyme topoisomerase present in the nucleus of body cells. Topoisomerase helps in the replication of DNA. This antibody is used for the diagnosis of scleroderma, also known as systemic sclerosis. Progressive systemic sclerosis affects different systems, like the skin, heart, lungs, kidneys and digestive tract, and is more common in women. Anti-Scl-70 antibodies are present in 15%-20% of people with scleroderma.
  • Anti-Jo-1 antibody: These antibodies are also known as anti histidyl transfer synthase antibodies. They formed against the enzyme anti histidyl transfer synthase, which helps in the formation of proteins in body. Anti-Jo-1 antibodies are present in people with autoimmune pulmonary fibrosis and in a small number of people with autoimmune myositis.
  1. Why is Extractable Nuclear Antigen (ENA) Antibodies panel performed?
  2. How do you prepare for an Extractable Nuclear Antigen (ENA) Antibodies panel?
  3. How is an Extractable Nuclear Antigen (ENA) Antibodies panel performed?
  4. Extractable Nuclear Antigen (ENA) Antibodies panel results and normal values

Your doctor may order an ENA panel if you show signs and symptoms suggestive of an autoimmune condition. Some common symptoms of autoimmune conditions are:

This test is only performed if you have a positive antinuclear antibody (ANA) test. A positive ANA test indicates that you have an autoimmune disorder, while an ENA panel determines which specific autoimmune disorder you have. 

The ENA panel can help in diagnosing autoimmune conditions like SLE, mixed connective tissue disease, Sjögren syndrome, scleroderma, autoimmune pulmonary fibrosis and autoimmune myositis.

Some of the symptoms of SLE are:

  • Extreme fatigue
  • Hair loss
  • Headaches
  • A butterfly-shaped rash across cheeks and nose
  • Painful or swollen joints
  • Fever
  • Abnormal blood clotting
  • Anaemia 
  • Swelling in feet, legs, hands and/or around eyes
  • Pain in the chest on deep breathing 
  • Sun- or light-sensitivity (photosensitivity)
  • Fingers turning white and/or blue when cold (Raynaud phenomenon)
  • Mouth or nose ulcers

The initial symptoms of mixed connective tissue disease are:

Other symptoms of mixed connective tissue disease are:

  • Inflammation in joints and muscles
  • High blood pressure within the blood vessels of the lungs (pulmonary hypertension)
  • Swollen "sausage-like" fingers which may be temporary or may progress into sclerodactyly (thin fingers with hardened skin and limited movement)

Some of the common symptoms of Sjögren syndrome are:

  • Dryness in nose or throat
  • Dry eyes and dry mouth
  • Vaginal dryness
  • Swollen glands, specifically in front of the ears and behind the jaw
  • Dry skin
  • Joint pain, swelling or stiffness
  • Skin rashes
  • Prolonged dry cough
  • Trouble urinating
  • Tingling and numbness in your toes and fingers

Scleroderma can present with some of the following symptoms:

  • Scarring of joints, skin and internal organs
  • Calcium bumps over fingers or other bony areas
  • Joint pain
  • Abnormal heart rhythms and heart failure
  • Scarring of the skin
  • Raynaud phenomenon
  • Swelling and thickening of fingertips
  • Scarring of the oesophagus (food pipe) which causes problems in swallowing and heartburn
  • Scarring of the lungs causing shortness of breath
  • Kidney disease
  • Spider-shaped veins
  • Sores on fingertips and knuckles
  • Patches of tight, shiny, darker skin that affect movement

Some symptoms of pulmonary fibrosis are: 

  • Shortness of breath, particularly during exercise
  • Achy joints and muscles
  • Fast, shallow breathing
  • Dry cough
  • Unexplained weight loss

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Symptoms of myositis include:

  • Trouble swallowing or breathing
  • Trouble rising from a chair
  • Tired feeling after standing or walking 
  • Difficulty climbing stairs or lifting arms
  • Muscle pain and soreness that last beyond a few weeks

ENA panel can also help monitor the progress of these conditions.

 No prior preparations are needed for these tests.

All of the tests in an ENA panel are done on a blood sample. So, for this test, your doctor will withdraw a few millilitres of blood from a vein in your arm. He/she will transfer the sample into a labelled bottle and send it to the laboratory for testing. 

After the test, you may have a bruise at the injection site, which may be painful but will fade away in a few days. If you feel dizzy during the test or feel uncomfortable at the sight of blood, please inform the technician or nurse so that they can help you feel at ease when performing the test.

Normal results:

Normal or negative results for antibodies in the ENA panel are as follows:

  • Anti-RNP: Less than 1 U (unit)
  • Anti-Sm: Less than 1 U
  • Anti-SSA: Less than 1 U
  • Anti-SSB: Less than 1 U
  • Scl-70: Less than 1 U
  • Anti-Jo-1: Less than 1 U

Abnormal results:

If your results are abnormal, it could indicate the following:

  • Anti-RNP: Mixed connective tissue disease, SLE, progressive systemic sclerosis/scleroderma
  • Anti-Sm: SLE
  • Anti-SSA and anti-SSB: Sjögren syndrome, rheumatoid arthritis, neonatal lupus, ANA-negative SLE
  • Scl-70: Scleroderma
  • Anti-Jo-1: Pulmonary fibrosis, autoimmune myositis

Disclaimer: All results must be clinically correlated with the patient’s complaints to make a complete and accurate diagnosis. The above information is provided from a purely educational point of view and is in no way a substitute for medical advice by a qualified doctor.

References

  1. Aggarwal Amita. Role of autoantibody testing. Best Practice & Research Clinical Rheumatology. 2014 December; 28(6): 907-920.
  2. Kavanaugh Arthur, Tomar Russell, Reveille John, Solomon Daniel H., Homburger Henry A. Guidelines for Clinical Use of the Antinuclear Antibody Test and Tests for Specific Autoantibodies to Nuclear Antigens. Archives of Pathology & Laboratory Medicine. January 2000; 124(1): 71-81.
  3. Ortega-Hernandeza Oscar-Danilo, Shoenfeld Yehuda. Mixed connective tissue disease: An overview of clinical manifestations, diagnosis and treatment. Best Practice & Research Clinical Rheumatology. 2012 Feb; 26(1): 61-72.
  4. Johns Hopkins Medicine [Internet]. The Johns Hopkins University, The Johns Hopkins Hospital, and Johns Hopkins Health System; Lupus Blood Tests
  5. South Tees Hospitals. NHS Foundation trust. National Health Service, U.K.; Anti-RNP Antibody
  6. National Kidney Foundation [Internet]. New York (NY). US; Lupus and Kidney Disease (Lupus Nephritis)
  7. Pagana KD, et al. Mosby’s diagnostic and laboratory test reference. 14th ed. Missouri: Elsevier; 2019. Anti–SS-A (RO), anti–SS-B (LA), and anti–SS-C antibodies (Anti-Ro, Anti-La, Sjögren antibodies). p 95,96.
  8. Genetics Home Reference [internet]. National Institute of Health: US National Library of Medicine. US Department of Health and Human Services; Systemic scleroderma
  9. Lupus Foundation of America [internet]. Washington D.C. (U.S.); Lupus symptoms
  10. Cedars Sinai [Internet]: Cedars Sinai Medical Center. Los Angeles. US; Scleroderma
  11. R Rich, T Fleisher, W Shearer, et al. Clinical Immunology Principles and Practice. Thirs edition. St. Louis, Mosby-Year Book, 2001, pp 60.1-60.24
  12. Targoff IN. Autoantibodies in polymyositis. Rheum Dis Clin North Am. 1992;18(2):455–482. PMID: 1378227.
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