Kevin J. Murray

Pathogenesis of juvenile chronic arthritis: genetic and environmental factors

Juvenile chronic arthritis (JCA) is a heterogeneous group of chronic arthropathies affecting approximately 1–3 children per 1000. The initial oversimplified classification into pauciarticular, polyarticular, and systemic onset types has been expanded in a World Health Organisation-International League Against Rheumatism report to include seven different types of disease.1 It is clear that the majority of children with JCA have a different disease from adults with rheumatoid arthritis, although the chronic arthropathies have some common clinical and pathological features. As a group, these diseases are generally considered to be autoimmune in origin with the evidence supporting this varying between types. There is a general female preponderance, characteristic chronic inflammatory infiltrates in the synovium and immune responses characterised by autoantibodies including antinuclear antibodies (ANA), IgM rheumatoid factor, and antibodies to heat shock proteins and the oncoprotein DEK. In addition and in common with many other autoimmune diseases, there are extensive and well documented associations with genetic markers, primarily, but not exclusively, within the major histocompatibility complex (MHC) or HLA region on the short arm of chromosome 6. It is anticipated that environmental triggering agents are also involved in the pathogenic process. In a recent review of a related disease, rheumatoid arthritis, the contribution of HLA genetics to pathogenesis was estimated to be approximately 37% with as yet unknown genes contributing further, with the balance being deemed largely due to environmental factors.2 The purpose of this review is to consider the relative contributions of genetic versus environmental factors as being causal in the various types of JCA.nnJCA is rarely familial so that a low index of suspicion for a simple genetic basis is in order. In early studies reported, Dr Barbara Ansell and Professor Eric Bywaters were able to identify family disease and concordance in twins. Subsequently multiplex families and sibling …

T-Cell receptor BV6S1 null alleles and HLA-DR1 haplotypes in polyarticular outcome juvenile rheumatoid arthritis

JRA is a complex of disease subtypes which are normally identified by clinical features such as age of onset and extent of joint involvement both at onset and during the course of the disease. We previously identified an association between TCR BV6S1 null allele and one subgroup of early-onset pauciarticular patients positive for HLA-DQA1*0101, an HLA haplotype predisposing to a polyarticular course of the disease. In this report we extend this observation by identifying an increased prevalence of this nonfunctional or null allele in the patients with a polyarticular disease course regardless of the mode of onset. This increase was most prominent in clinical subsets that have early onset of the disease and a polyarticular outcome. In one clinical group, stratification of patients by the HLA allele DQA1*0101 strengthened the association considerably. This implies that there is an increased genetic load defined by specific alleles of both MHC and TCR genes.

A54: Insulin Sensitivity Is Improved in sJIA Children With Insulin Resistance After Tocilizumab Treatment: Results From the TENDER Study

In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin‐6 (IL‐6) is postulated to play a mechanistic role in IR. The aim of this study was to evaluate the degree of IR among children with systemic juvenile idiopathic arthritis (sJIA) and to determine whether treatment with tocilizumab (TCZ) results in attenuation of IR in sJIA.

PReS-FINAL-2188: Insulin sensitivity is improved in sjia children with insulin resistance after tocilizumab treatment: results from the tender study.

In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin-6 (IL-6) is postulated to play a mechanistic role in IR.

Two subtypes of symptomatic joint hypermobility: a descriptive study using latent class analysis

Objective To investigate a cohort of children with symptomatic joint hypermobility. Methods Case notes for 318 children with joint hypermobility attending a rheumatology clinic were reviewed for clinical presentation, medical history, psychosocial factors and physical examination findings. Seven key variables were extracted and used as indicator variables in a latent class analysis to estimate the presence and number of subgroups of children with symptomatic joint hypermobility. Results Two subgroups with differing clinical presentations were identified accounting for age and gender: an ‘athletic-persistent’ class (62%) characterised by higher probabilities for recurrent and chronic musculoskeletal pain, and less severe hypermobility; and a ‘systemic-profound’ class (38%) characterised by generalised hypermobility, recurrent musculoskeletal pain, gastro-oesophageal reflux and motor delay. Conclusion Findings suggest the presence of two distinct presentations of children with hypermobility. This finding may be important for clinical decision-making and management of this group of children.