JIA Leads in Pediatric Rheumatology Research

Organized collaborations and advances in technology have contributed to improved treatment of rheumatic diseases that affect children, according to a review of advances in pediatric rheumatology published in the new issue of Nature Reviews Rheumatology. Recent research in pediatric rheumatology has revealed the pathogenesis of many diseases, state the authors, led by Seza Ozen of Hacettepe University in Turkey. One major contribution has been the definition of diseases that have the same phenotype as corresponding complex diseases. An example is the identification of deficiency of adenosine deaminase 2 (ADA2). In this disease mutations in a single gene, CECR1, lead to a disease similar to polyarteritis nodosa. The authors note another genetic mutation that mimics a complex disease, the LACC1 gene, which causes a form of systemic juvenile idiopathic arthritis (JIA). Through gene expression profiling, researchers have discovered pathogenetic biomarker signatures in pediatric rheumatic dis¬eases. Virtually all patients with pediatric systemic lupus erythematosus (SLE) have an interferon signature; an interferon signature is found in only about half of adult SLE patients.  The term interferonopathies, introduced in 2011, now includes at least 12 monogenic diseases in which the innate immune response leads to interferon production and related autoinflammatory features.  Researchers have also identified that IL-1 has a leading role in systemic JIA, and IL-1-related diseases are now grouped as autoinflammatory diseases. A multinational, multidisciplinary registry now enables pediatricians to collect information about the clinical features and demographics of autoinflammatory diseases. “Studies of treatments for JIA have flourished with international collaboration. In other rheumatic diseases, however, multicenter treatment studies in children are lacking, owing mainly to ethical considerations and a lack of tools that enable the use of validated classification criteria (often used as diagnostic criteria in practice),” researchers wrote. A number of genome-wide association studies in JIA have confirmed the association with three previously known JIA risk loci and identified 14 new loci associated with risks of JIA. Other researchers have focused on the autoimmune inflammatory environment of the rheumatoid joint and their results suggest that regulatory T cells play a role in defining the course of arthritis. In addition, in the past decade pediatricians have succeeded in developing classifications to guide physicians in the diagnosis of juvenile scleroderma and the common childhood forms of vasculitis. Another important contribution by pediatricians has been in defining S100 proteins as biomarkers of inflammation, in particular for the risk-adapted stratification of patients with JIA. “Pediatric rheumatology is surely progressing in the quest to better understanding its diseases. The relevant research will enable us to better manage our young patients, who have a long life-expectancy,” the authors wrote.  

References:

Seza Ozen. “Decade in review-paediatric rheumatology:  A field on the move,” Nature Reviews Rheumatology. 11, 625–626 (2015) doi:10.1038/nrrheum.2015.130. Published online 22 September 2015