Reviews & Analysis

The contributions of key cytokines in rheumatoid arthritis (RA) pathogenesis, including TNF, IL-1, JAK-dependent cytokines, GM-CSF and chemokines, can be considered not only individually, but also in the context of an overall 'RA tissue response'. In this Opinion article, the authors provide an overview of the roles of cytokines in the innate, adaptive and stromal immune responses, and discuss how systematic analysis of cytokine pathways could yield new insights into disease pathogenesis and facilitate stratification for therapy.

Lipopolysaccharide derived from gastrointestinal microbiota contributes to systemic inflammation and obesity. Huang and Kraus propose that lipopolysaccharide is a major risk factor for osteoarthritis (OA), and suggest that therapeutic strategies for the reduction of systemic levels of lipopolysaccharide should be considered for prevention and treatment of OA.

This article presents the concept that Behçet disease and several spondyloarthropathies might have a common immunopathogenetic basis. The authors propose that barrier dysfunction in environmentally exposed organs, and aberrant innate immune reactions at sites of mechanical stress, trigger secondary adaptive immune CD8⁺T-cell responses characterized by prominent neutrophilic inflammation. The differential immunopathology of these 'MHC-I-opathies' could reflect antigenic differences in target tissues.

Treatment optimization studies have paved the way for success of new therapies in paediatric oncology. The majority of children with cancer are treated within treatment optimization study protocols (TOSPs), but this is not the case for children with common rheumatic diseases such as juvenile idiopathic arthritis. In this Opinion article, Niehues suggests the recruitment of children with rheumatic diseases into TOSPs, making use of rheumatology research networks already established, would secure standardized treatments and outcome measures and could improve patient care considerably.

Observational studies are increasingly used to evaluate the safety and effectiveness of drugs for rheumatoid arthritis, but these studies are limited by inherent biases, including confounding by indication. This Perspectives article describes how these methodological limitations could be overcome by using the active-comparator design and the new-user design.

Genetic factors play an important part in the disease heterogeneity observed in patients with rheumatoid arthritis (RA). Genome-wide association studies (GWAS) have linked common single-nucleotide polymorphisms with the risk of developing RA, but have also highlighted the genetic heterogeneity between Asian and European patients with this disease. In this Perspectives article, the authors discuss recent advances from GWAS in Asian patients with RA, and suggest that better knowledge of the interface between genetic and environmental factors could help our understanding of the disease.

Kim et al. hypothesize that IL-21 is crucial to the pathogenesis of primary Sjögren syndrome (pSS), focusing on evidence of an interplay between the innate and adaptive immune responses mediated by the effects of IL-21 on immune cells. This new perspective might ultimately offer insight into novel approaches to the treatment of pSS.