Extractable nuclear antigens (ENAs) are over 100 different soluble cytoplasmic and nuclear antigens. They 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. 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. 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. It is usually done as a follow up to a positive antinuclear antibody (ANA) test and when 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 one develops autoantibodies, one 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. The use of anti-ENA autoantibody tests can serve as additional verification of an autoimmune disorder, because a positive ANA test alone does not suffice for diagnosis. In fact, low levels of ANAs can be found in healthy patients. The applications of anti-ENA testing varies from excluding patient groups from specific groups, connective tissue diseases, and to monitor disease activity. In essence, it allows clinicians to exclude specific autoimmune disorders if a particular autoantibody is not present, and allows clinicians to track progression of a disease if the levels of these autoantibodies increase or decrease. To confirm the presence of anti-ENAs, it is currently recommended to use two or more methods to confirm anti-ENAs to avoid false positives. The diagnosis of autoimmune connective tissue diseases (CTDs) is done through analysis of clinical symptoms and signs, but also through the identification of the autoantibodies directed against nuclear antigens. A 2002 paper also seeks to compare the diagnostic tests used in immunology laboratories to