Historical Perspective on Antinuclear Antibody Testing

Serum factors binding to cell nuclei were first described in the 1940s, and the antibodies responsible for the binding to self (autoantibodies) were discovered in the late 1950s. Routine standardized testing using a cell line (HEp-2) started in the 1980s and continues to evolve. In addition to the classic immunofluorescence assay (IFA), various immunochemical techniques have been developed for the measurement of antinuclear antibodies (ANAs). The complexity of ANA IFA pattern reading and the varying sensitivities, specificities, and overall clinical performance of the alternative methods have often generated controversies and sometimes even confusion among healthcare providers and laboratorians. A better understanding of the historical roots of ANA testing can aid in understanding these controversies and assist with selecting the best-performing methods. In this review, we present historic and contemporary ANA testing methods, highlighting the pros and cons of each. We also provide an overview of the current practice of ANA testing based on several recent large laboratory surveys. For optimal patient care, it is critical that clinicians and laboratorians using ANA testing understand the performance and limitations of the methods used by their institutions, as well as the meaning of the test results. Recently published surveys and standardization efforts initiated by several stakeholder scientific organizations will likely lead to new ANA diagnostic guidelines, to be followed by an improvement in testing practices, management, and outcomes for patients with autoimmune disorders.