Q: I had two ANA tests that ran 9 months apart. The first was 1:320 speckled and the second was 1:40 speckled. How could there be such a big difference? The second doctor also ran Anti-RNP, Anti-smith, Anti-SSA, Anti-SSB. All were 1:00. Are they positive or negative?

A:Anti-nuclear antibodies (ANA) are an unusual type of gamma-globulins found in patients with certain autoimmune diseases i.e. patients whose immune system is predisposed to cause inflammation against their own body tissues. ANAs are directed against certain components found in the nucleus of a cell in the body. Antibodies directed against structures in our own body arise as part of the normal immune response to various infections. The persistence of such antibodies, in the presence of suggestive clinical features, is supportive and sometimes diagnostic of autoimmune disease. An ANA test is needed if there is a reasonable suspicion of SLE from history, physical findings or the results of routine tests such as the CBC (leukopaenia, thrombocytopaenia) as ANA may be found in a variety of conditions and in normal individuals. The random chance of a false positive in normal individuals is considerably greater than a true positive, unless the clinician selects only individuals with a reasonably high possibility of having the disease before testing. Therefore, careful selection of patients to be tested is of great importance as improper use of ANA testing can lead to misinformation, incorrect diagnoses and a waste of money. This is because, even with the newest tests, about 5% (1 out of 20) of normal individuals will give a weakly positive result and ANA should never be ordered as a routine screening test. A positive ANA result in a patient with no or minimal features of SLE can be misleading or worse because it may cause the clinician to order unnecessary tests. These antibodies can be detected by several techniques like enzyme-linked immunosorbent assay (ELISA), Indirect immunofluorescence (IF), Counter immunoelectrophoresis (CIE) and Immunoblotting assay (IB). The sensitivity and specificity of various techniques varies as does the format of their reporting which may explain this discrepancy. The speckled pattern is highly related to SLE, mixed connective tissue disease, Sjögren’s syndrome, polymyositis or scleroderma. You should discuss this with your doctor who will be best placed to advise you.