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There are many people who have what is called "Negative ANA Lupus". 95-98% of people with lupus do have a positive test for ANA. But, around 5% of people can have a negative ANA test, and still have lupus. Therefore, if you have some of the symptoms and signs of lupus, but with a negative ANA test, your doctor will try to eliminate a large number of conditions that can have a positive ANA test before they diagnose you with Lupus (thus the request for additional tests). These other conditions, which can mimic lupus and have a positive ANA test, include mixed connective tissue disease, undifferentiated connective tissue disease, scleroderma, myositis, rheumatoid arthritis and several others. Some times, it may take a while before a clear diagnosis can be made, because these diseases, like lupus, can sometimes evolve slowly, symptoms come and go and symptoms change. So, the diagnostic process may take some time.
Lupus patients who have a negative ANA test usually have a positive test for anti-Ro (also called anti-SSA) or anti-La (anti-SSB). The ANA screen can not be relied upon for its negative predictive value. A negative ANA may not exclude you from having these other autoimmune conditions.
ENA testing (antibodies to "extractable nuclear antigens") assists in defining subsets of autoimmune diseases, with the most important antigens and their clinical associations listed below. Doctors perform the ENA screening using an enzyme-linked immuno-sorbent assay ( ELISA) and also uses the counter-immunoelectrophoresis ( CIE) assay as a confirmatory test. The ELISA results have enhanced sensitivity, especially for SSA, SSB and Scl-70 antibodies.
The anti-Sm antibody - Antibody to the Smith antigen is a protein that helps DNA stay in its correct shape as it goes about its business directing the cell how to do its work. Together, anti-Sm, anti-RNP, anti-Ro/SSA, and anti-La/SSB are known as ENA antigens. A positive test, like anti-DNA, generally means that lupus is present. False positive tests are very rare.
However, a negative test does not mean that lupus is not present, since other tests can still be positive. Most persons with lupus have either anti-DNA or anti-Sm antibodies.
I hope that I've answered your question, let me know if you need anything further.
Peace and Blessings