Extractable nuclear antigen

Extractable Nuclear Antigens (ENAs) are a type of over 100 different soluble cytoplasmic and nuclear antigens.

Etiology

These nuclear antigens 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, Jo1.

Nuclear riboproteins

• Most ENAs are part of spliceosomes or nucleosomes complexes and are a type of small nuclear ribonucleoprotein (snRNPS).
• The location in the nucleus and association with spliceosomes or nucleosomes results in these ENAs being associated with additional RNA and proteins such as polymerases.
• This quality of ENAs often makes it difficult to purify and quantify their presence for clinical use.

ANA testing guidelines

Clinical Applications

An extractable nuclear antigen panel, or an ENA Panel, tests for presence of autoantibodies in the blood that react with proteins in the cell nucleus. Usually done as a follow up to a positive antinuclear antibody (ANA) test and one is showing symptoms of an autoimmune disorder. The ANA tests for the presence or absence of autoantibodies, while the ENA panel evaluates which proteins in the cell nucleus the autoantibodies recognize. The ENA panel helps diagnosis, distinguish between, and monitor the progression of autoimmune diseases and is performed with a simple blood draw. While the levels of autoantibodies may fluctuate through one's life, once you develop autoantibodies, you will always have them. Autoantibodies to these antigens are associated with particular connective tissue disorders. Indeed, in 84.3% of positive anti-ENA samples, ANA reagents were also found.

ENA

Anti-ENA is a grouping of antibodies often used to screen for mixed connective tissue disease (MCTD), Sjögren's syndrome and systemic lupus erythematosus and commonly is composed of six tests:

• anti-Sm (for SLE)
• anti-RNP (for MCTD)
• anti-La/anti-SS-B (for Sjögren's)
• anti-Ro/anti-SS-A(for Sjögren's)
• anti-Scl70 (for Scleroderma)
• anti-Jo (for Dermatomyositis)

Sensitivity and specificity of these tests depends on the type of assay employed, and will therefore vary by lab. The following table illustrates the sensitivity and specificity of ENA antibodies at detecting SLE with the ELISA technique.

Antibody (tested using ELISA)	Sensitivity (%) for SLE	Specificity (%) for SLE
Anti-Ro (SS-A)	61	80-93
Anti-La (SS-B)	27-35	88-97
Anti-Sm	34-45	88-100
Anti-RNP	39-64	84-97

In addition, the use of ENA testing has also been used for the study of wheat related disorders such as celiac disease. A study conducted in 2018 screened patients with wheat related disorders for 10 anti-ENA antibodies.

• SSA (Ro)
• SSB (La)
• RNP/Sm
• Jo-1
• Sm
• Scl-70
• Chromatin
• Centromere
• Histone
• RNA polymerase III

73% of celiac disease subjects tested positive for anti-histone and was the most prevalent, which is typically associated with Drug-induced lupus erythematosus. This implicates a high probability of an autoimmune disorder in patients with wheat-related disorders.

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