Lack of standardisation of ANA and implications for drug development and precision medicine

The recent article by Pisetsky et al 1, showing data derived from a comparison between different antinuclear antibody (ANA) assays in a cohort of patients with established systemic lupus erythematosus (SLE), addresses several important and current aspects of ANA detection. In addition, the study touches on clinical trials for ANA-associated rheumatic diseases (AARDs) and raises several relevant points  that will be discussed in this letter. One of the fundamental questions around ANA testing is: “What is an ANA and what are diagnostic tests actually measuring?”. In other words, there is no clear definition of what is and what should be included in ANA testing.2 For example, technically antibodies to cytoplasmic antigens do not belong to ANA, but can help in the diagnosis of certain AARDs and are in some countries reported as ANAs. This is important in the context of SLE as about 15%–30% of patients with SLE have anti-ribosomal antibodies that typically present with a cytoplasmic staining pattern. However, the cytoplasmic pattern need to be clearly defined as patients with other autoimmune diseases might also present with a cytoplasmic pattern (eg, myositis or autoimmune liver disease), although with different staining pattern.3 Although the ANA indirect immunofluorescence (IIF) test has been recommended as the method of choice,4 the method is not without limitations.5 In addition, novel solid phase assays (SPAs) have significantly improved6 and are increasingly being used as the screening test of choice in high-throughput laboratories for the detection of ANA.5 However, it remains a matter of debate whether or not SPA such …