The use of laboratory tests in the diagnosis of SLE

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Abstract
Any antibody to nuclear components is an ANA. Most patients with ANAs do not have SLE, but most people with SLE have ANAs. The most common screening test is IIF on rodent liver or human epithelial (HEp2) tissue,3 although ELISA tests are available.4, 5 Lupus erythematous cells simply represent nuclei opsonised by ANAs and are no longer used in diagnosis. Although ANAs are very sensitive for SLE, positive ANAs are common, especially in unwell elderly individuals.6– 8 Therefore, ANAs have low PPV for SLE in unselected populations or when present in low titres,6, 9 and are not diagnostic. One in three healthy people have detectable ANAs on HEp-2 cells at a screening dilution of 1/40 and one in 20 will be positive at 1/160. HEp-2 cells produce more positive ANAs than rat tissue, and some ANAs (for example, anticentromere antibodies) can only be reliably detected on HEp-2 substrate. Although “ANA negative” SLE is reported,10 it is not clear whether this is the result of a technical artifact or whether a subgroup of SLE exists. Most ANA negative patients are positive in DNA or ENA assays or when screened by IIF on a different substrate. ARA criteria refer to “abnormal” titres of autoantibodies, but there is no cut off value that will absolutely distinguish normality from autoimmune disease. In general, higher titres are more meaningful, particularly in young patients. ANA measurement is at best semiquantitative, and is poorly standardised between laboratories owing to the lack of suitable reference preparations. The precision and accuracy of the technique depends on the assay configuration, the quality control procedures, and the experience of the reader (table 4). Patterns might suggest antibody specificities but are not diagnostic (table 5). Most clinically relevant ANAs are IgG antibodies and the detection of IgM antibodies usually reduces the clinical usefulness of the test.11, 12 Antibody class switching to IgG usually occurs in established autoimmunity, and many low titre, low affinity IgM autoantibodies are found in healthy individuals. The absence of ANAs at titres of 1/160 or less makes SLE very unlikely. Approximately 10% of SLE like disease is drug induced and potentially reversible. However, drug induced ANAs are more common than disease, and careful interpretation of the possible clinical relevance of an ANA in this context is needed. Each laboratory should configure its protocol for an appropriate sensitivity/specificity compromise, should perform adequately in local and national external quality assessment (EQA) schemes, and should not interpret results without reference to the clinical details. More specific and precise tests should be performed in ANA positive individuals to determine the autoantibody specificity (table 5).