Autoantibodies to Extractable Nuclear Antigens: Making Detection and Interpretation More Meaningful

The diagnosis of autoimmune connective tissue diseases (CTDs) depends not only on the identification of patients manifesting disease-associated groups of clinical symptoms and signs but also on the detection of autoantibodies directed against nuclear or cytoplasmic antigens. Clinicians, however, often do not fully understand the appropriate application and limitations of these tests (10, 25). Over the last decade, new methods of performing immunol-ogy tests have been introduced into laboratory practice, prin-cipally to facilitate the processing of large numbers of samples. This rapid change has compounded the problems that result when requesting clinicians are unaware of the performance characteristics of laboratory tests. Testing for autoantibodies to extractable nuclear antigens (ENAs) provides a cogent example. Interpretation of the clinical significance and role of these antibodies in the diagnosis and management of CTDs is based on information gained by using gel-based techniques, such as double immunodiffusion (DID) and counterimmunoelectro-phoresis (CIEP) (11). The disease associations linked to the findings may no longer hold true with newer techniques, such as enzyme-linked immunosorbent assays (ELISAs) and immu-noblotting (IB) assays. For example, anti-Sm antibodies de-tected by gel-based techniques are highly specific for systemic lupus erythematosus (SLE) and form part of the revised Amer-ican Rheumatism Association criteria for the classification of SLE (26). However, the detection of anti-Sm antibodies by ELISAs in some patients who do not have SLE has diluted the strength of this formerly very powerful clinical association (12). Clinicians not aware of this subtle difference in the perfor-mance characteristics of the ELISA method may overdiagnose