SLE criteria are by necessity still based on clinical (and immunological) criteria items.

Introduction: The 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) rely on clinical and routine immunological items. The criteria have anti-nuclear antibodies (ANA) as an obligatory entry criterion; items are weighted and ordered in domains. While demonstrating good sensitivity and specificity, the lack of a more molecular approach to some came as a disappointment.

Areas Covered: Based on a non-systematic literature search, this review covers items investigated in the EULAR/ACR classification criteria project, but not included in the set of criteria. It demonstrates data on the importance of the criteria and analyses implications of multiomics studies started around the same time as the criteria project. We also discuss data on the type-I interferon signature and on other cytokines, as well as on complement proteins and their split products. The final part deals with the variability in disease and the apparently random pattern of autoantibodies and organ manifestations in individual patients.

Expert Opinion: We believe that the EULAR/ACR criteria are a relevant step toward the right direction. A more uniform molecular approach will not be feasible as long as the molecular mechanisms underlying the tendency toward producing multiple autoantibodies are not better understood.