From bench to bedside and back again: translational research in autoinflammation

Abstract

Translational research approaches brought major changes to the understanding and treatment options of autoinflammatory diseases. Patients with common complex multifactorial diseases such as systemic-onset juvenile idiopathic arthritis (sJIA), and particularly those with rare monogenic autoinflammatory diseases such as cryopyrin-associated periodic syndromes (CAPS) or TNF receptor-associated periodic syndrome (TRAPS), benefited from a deeper understanding of the pathophysiological mechanisms and new treatment options emerging from preclinical studies. The study of IL-1 and IL-6 in this context led to novel therapies by forward translation. Conversely, effective treatment of sJIA and TRAPS with IL-1 blockade stimulated reverse translational efforts to study the pathophysiology of these cytokines in autoinflammatory diseases. These translational efforts led to the discovery of biomarkers such as S100 proteins, IL-18 or serum amyloid A, which are components of the inflammatory process, support diagnosis and allow for monitoring of disease activity, helping to predict patient outcomes. The ongoing characterization of autoinflammatory diseases in individual patients has led to classification into heterogeneous subgroups. Further characterization of relevant subgroups and the design of tailored treatment regimens, as well as the identification of new therapeutic targets and treatment options, are the major future challenges in the field of autoinflammatory diseases, particularly for paediatric rheumatologists.