Extractable Nuclear Antigen Antibodies (ENA) Panel

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Also Known As:
Antibodies to Saline-extracted Antigens
Anti-RNP
Anti-Ribonucleoprotein
Anti-U(1)RNP
Anti-SmRNP
Anti-SSA
SSA (Ro)
Anti-Sjögren Syndrome A
Anti-SSB
SSB (La)
Anti-Sjögren Syndrome B
Anti-Sm (Sm)
Smith Antibody
Scl-70
Anti-Topoisomerase
Scleroderma Antibodies
Anti-Jo-1
Antihistidyl Transfer RNA Synthase Antibodies
ENA Panel

Formal Name:
Extractable Nuclear Antigen Antibodies

This article was last modified on November 9, 2021

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At a Glance

Why Get Tested?

To help diagnose and distinguish between autoimmune disorders as well as to monitor autoimmune disease progression

When To Get Tested?

When your antinuclear antibody (ANA) test is positive and you have symptoms that suggest an autoimmune disorder; when monitoring the activity of an autoimmune disorder

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

Looking For Test Results?

Looking For Reference Ranges?

You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Testing.com. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.

Testing.com is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

An extractable nuclear antigen (ENA) panel detects the presence of autoantibodies in the blood that react with proteins in the cell nucleus. These proteins are known as “extractable” because they can be removed from cell nuclei using saline and represent six main proteins (Ro, La, Sm, RNP, Scl-70 and Jo1).

Autoantibodies are produced when a person’s immune system mistakenly targets and attacks the body’s own tissues. This attack can cause inflammation, tissue damage, and other signs and symptoms that are associated with an autoimmune disorder.

Certain autoimmune disorders are characteristically associated with the presence of one or more anti-ENA antibodies. Autoantibody association can aid in the diagnosis of an autoimmune disorder and help distinguish between other autoimmune disorders.

The ENA panel typically consists of a group of 4 or 6 autoantibody tests. The number of tests performed will depend on the laboratory and the needs of the healthcare practitioners and patients it serves. Individual ENA panel tests can also be ordered separately.

A 4-test ENA panel will include:

Autoantibody Test	Formally Known As
Anti-RNP	Anti-U(1)RNP, Anti-Ribonucleoprotein
Anti-Sm	Smith Antibody
Anti-SS-A (Ro)	Anti-Sjögren Syndrome A
Anti-SS-B (La)	Anti-Sjögren Syndrome B

A 6-test ENA panel will include the four tests listed above as well as:

Autoantibody Test	Formally Known As
Anti-Scl-70	Scleroderma Antibodies; anti-topoisomerase
Anti-Jo-1	Anti-Histidyl Transfer RNA Synthase Antibodies

Common Questions

How is the test used?

The ENA panel may be used as follow-up testing to a positive ANA test to help diagnose an autoimmune disorder. Testing may be used to help distinguish between autoimmune disorders as well as to monitor autoimmune disease progression.

The 4-test ENA panel is used to help diagnose mixed connective tissue disease (MCTD), lupus (SLE), and Sjögren syndrome. The 6-test ENA panel can also help identify scleroderma and polymyositis/dermatomyositis. For more on these diseases, see the links under Related Content below.

An ENA panel may also be used to monitor the activity of a particular autoimmune disorder in conjunction with clinical examination.

When is it ordered?

An ENA panel is ordered when a person has signs and symptoms that could be due to an autoimmune disorder and has a positive ANA test. Signs and symptoms of autoimmune disorders are highly variable and can involve several different areas of the body. They may include:

Fever and persistent fatigue
Muscle pain
Joint swelling and/or pain
Skin rash
Hair loss or loss of scalp hair
Sensitivity to ultraviolet light
Raynaud phenomenon
Protein in the urine (proteinuria)
Neurologic symptoms such as seizures, depression, psychoses
Hemolytic anemia (low red blood cell count) or leukopenia (low white blood cell count)

An ENA panel will not be ordered when a person has a negative ANA test. The ANA test evaluates the presence or absence of autoantibodies, while the ENA panel aims to determine to what proteins in the cell nucleus the autoantibodies recognize. If an ANA test is negative, then the person is extremely unlikely to test positive for a specific antinuclear antibody (which is what the ENA panel tests).

The ENA panel, or one or more of its component tests, may be repeated when initial test results are negative but clinical signs and symptoms persist. Testing may also be ordered when a person has been diagnosed with an autoimmune disorder and at some point develops symptoms that may be due to an additional autoimmune disorder. A healthcare practitioner also may order testing to monitor the activity and/or progression of a known autoimmune disorder.

What does the test result mean?

Diagnoses of autoimmune diseases are typically based on the characteristic signs and symptoms and on results of autoantibody tests. ENA panel results aid in detecting and distinguishing between different autoimmune disorders. Studies have shown that each of these autoantibodies is frequently detected in people who have a specific autoimmune disorder and is less frequently detected or not detected in those without the disease.

The pattern of positive and negative results obtained with an ENA panel is evaluated in conjunction with the person’s clinical findings (signs and symptoms). If someone has clinical findings that suggest a specific autoimmune disorder and the corresponding ENA autoantibody is positive, then it is likely that the person has that condition.

If an individual has symptoms but the autoantibody is not present, it may mean that symptoms are due to another condition.

Interpretation of results for the tests included in an ENA panel are provided in the table below. A positive test result means that the person has more of that autoantibody in their blood than the designated reference value.

Autoantibody Test	Results That Support an Autoimmune Disorder Diagnosis
Anti-RNP	Positive result seen in 95-100% of mixed connective tissue disease (MCTD) cases; may also be positive with lupus and scleroderma
Anti-Sm	Positive result seen in 30% of those with lupus; very specific antibody marker for this disease
Anti-SS-A (Ro)	Positive result seen in 75% of those with Sjögren syndrome; may also be positive with lupus and scleroderma
Anti-SS-B (La)	Positive result seen in 60% of those with Sjögren syndrome; may also be positive with lupus and scleroderma; rarely present without anti-SS-A
Anti-Scl-70	Positive result seen in 60% of those with scleroderma; highly specific antibody marker for this disease
Anti-Jo-1	Positive result seen in 30% of those with polymyositis; may be positive with pulmonary fibrosis

Is there anything else I should know?

ENA are referred to as “extractable” or “saline-extracted” because of the laboratory method originally used to discover and work with these antigens. More than 100 antigens have been identified in this way, but only a few are clinically relevant and routinely tested.

Will my ENA autoantibodies ever go away?

Levels may fluctuate, but once a person has developed an autoantibody, he or she will continue to have it.

Can the ENA panel be performed at my healthcare practitioner's office?

No. The ENA tests require specialized equipment and skilled laboratory personnel. Your sample will need to be sent to a reference laboratory that performs these tests.

How long will it take for results?

This depends on the laboratory performing the testing. Since this is specialized testing and your sample may be sent to a reference laboratory, it may take several days for results to be available.

My doctor ordered only a 4-test ENA panel, not a 6-test ENA panel. Will something be missed?

The panel performed will usually be the one offered by the laboratory that tests your sample. If a 4-test panel is ordered and your doctor is interested in additional tests, he or she can order the others separately as needed to ensure that nothing is missed.

View Sources

Sources Used in Current Review

2017 review completed by Boris Calderon, MD, DABCC, FAACC, Associate Medical Advisor, Eli Lilly and Company.

Aggarwal A. Role of autoantibody testing. Best Pract Res Clin Rheumatol. 2014 Dec;28(6):907-20. doi: 10.1016/j.berh.2015.04.010. Epub 2015 May 23. Available online at http://www.sciencedirect.com/science/article/pii/S1521694215000170?via%3Dihub. Accessed on 6/15/2017.

Ortega-Hernandez O, Shoenfeld Y. Mixed connective tissue disease: An overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2012 Feb;26(1):61-72. doi: 10.1016/j.berh.2012.01.009. Available online at http://www.sciencedirect.com/science/article/pii/S1521694212000101. Accessed on 6/15/2017.

Arthur Kavanaugh, Russell Tomar, John Reveille, Daniel H. Solomon, and Henry A. Homburger. (2000) Guidelines for Clinical Use of the Antinuclear Antibody Test and Tests for Specific Autoantibodies to Nuclear Antigens. Archives of Pathology & Laboratory Medicine: January 2000, Vol. 124, No. 1, pp. 71-81. Arch Pathol Lab Med. 2000 Jan;124(1):71-81. Available online at http://www.archivesofpathology.org/doi/full/10.1043/0003-9985%282000%29124%3C0071%3AGFCUOT%3E2.0.CO%3B2. Accessed on 6/15/2017.

Sources Used in Previous Reviews

(© 1995-2010). Unit Code 89035: Antibody to Extractable Nuclear Antigen Evaluation, Serum. Mayo Clinic, Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/89035. Accessed March 2010.

(© 2006-2010). Extractable Nuclear Antigen Antibodies (RNP, Smith, SSA, & SSB): 0050652. ARUP’s Laboratory Test Directory [On-line information]. Available online at http://www.aruplab.com/guides/ug/tests/0050652.jsp. Accessed March 2010.

Hill, H. and Tebo. (Updated 2009 November). Mixed Connective Tissue Disease – MCTD. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/MCTD.html?client_ID=LTD#. Accessed March 2010.

Hill, H. and Tebo. (Updated 2009 August). Connective Tissue Diseases. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/ConnectiveTissueDz.html?client_ID=LTD. Accessed March 2010.

(© 1995-2010). Unit Code 83631: Connective Tissue Diseases Cascade, Serum. Mayo Clinic, Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=83631. Accessed March 2010.

Klein-Gitelman, M. (Updated 2009 September 29). Mixed Connective Tissue Disease. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1006966-overview. Accessed March 2010.

Hildebrand Jr., G. and Battafarano, D. (Updated 2009 July 24). Undifferentiated Connective Tissue Disease. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/334482-overview. Accessed March 2010.

Hajj-ali, R. (Revised 2008 February) Mixed Connective Tissue Disease (MCTD). Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec04/ch032/ch032c.html. Accessed March 2010.

Bartels, Christie M., et al. (Updated Jan. 28, 2013.) Systemic Lupus Erythematosus (SLE) Workup. Medscape online. Available online at http://emedicine.medscape.com/article/332244-workup. Accessed January 2014.

Orton, Susan M., et al. (March 2004). Practical Evaluation of Methods for Detection and Specificity of Autoantibodies to Extractable Nuclear Antigens. American Society for Microbiology, Clinical and Vaccine Immunology online. Available online at http://cvi.asm.org/content/11/2/297.full. Accessed January 2014.

Antibodies to Extractable Nuclear Antigens. Children’s Hospitals and Clinics of Minnesota. Available online at http://www.childrensmn.org/Manuals/Lab/FlowCyt/018959.pdf. Accessed January 2014.

Kavanaugh, Arthur, et al. (January 2000.) Guidelines for Clinical Use of the Antinuclear Antibody Test and Tests for Specific Autoantibodies to Nuclear Antigens. Archives of Pathology and Laboratory Medicine. Available online through http://www.archivesofpathology.org. Accessed January 2014.

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Extractable Nuclear Antigen Antibodies (ENA) Panel

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