European League against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus: the laboratory immunologist’s point of view
Authors: Maria Infantino, Mariangela Manfredi, Nicola Bizzaro
Journal: Annals of the Rheumatic Diseases (2019)

European League against Rheumatism/ American College of Rheumatology classification criteria for systemic lupus erythematosus: the laboratory immunologist's point of viewWe read with great interest the new European League against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) by Aringer et al, 1 that recommend a positive antinuclear antibody (ANA) test as an entry criterion for SLE classification.According to these criteria, ANA testing has to be performed by a highly sensitive screening method before initiating the cascade work algorithm.This is a strategic move compared with the previous criteria by the Systemic Lupus International Collaborating Clinics (SLICC) 2 in which ANA was considered just one of the immunological items together with the more specific antibodies against Sm and dsDNA.With this new concept, ANA testing has been separated from its corresponding level tests, strengthening the idea that ANA is necessary to define the clinical lupus phenotype.However, as laboratory immunologists we have some concerns about the ANA definition both in the previous and new criteria.The SLICC criteria which considered 'an ANA above laboratory reference range' as a criterion, left a great deal to arbitrariness about which method to use, and when the indirect immunofluorescence (IIF) method on HEp-2 cells is used, to the discriminating screening titer.Referring instead to the new classification criteria, we would like to note that the provision 'Testing by immunofluorescence on HEp-2 cells or a solid phase ANA screening immunoassay with at least equivalent performance' is somehow inaccurate, in that equivalence might be understood in this context in terms of sensitivity at the expense of specificity, which is a hallmark for classification purposes. 3While we acknowledge that specificity can be achieved by completing the classification algorithm and that the ACR/EULAR decision has been made in view of ongoing work on the standardisation of autoimmune diagnostics and its potential future advances, we maintain that this is a risky definition that might be misinterpreted, thereby encouraging the use of alternative methods, even when they lack (or provide suboptimal) clinical specificity.5][6] The great majority of studies performed in recent years [7][8][9] have mainly analysed the performance of new solid-phase screening assay, the so-called connective tissue disease screen test, which is currently the main 'competitor' to the ANA-IIF, having shown itself to be the closest in terms of sensitivity and specificity. 10 11However, since a lot of different methods are available today to the clinical lab, they can be inappropriately used as an alternative to the ANA-IIF test, without a solid evidence of being really equivalent.Therefore, efforts in standardising diagnostic tests and their brisk evolution and perfection make it fundamental nowadays not only to suggest the test name among the criteria, but to define and take a strong position on the method to use, and better yet, on what method not to use.