T-cell activation without proliferation in juvenile idiopathic arthritis

A study was done to determine if the differentiation and activation phenotype of T cells in synovial fluid (SF) from patients with juvenile idiopathic arthritis (JIA) is associated with T-cell proliferation in situ. Mononuclear cells were isolated from 44 paired samples of peripheral blood and SF. Differentiation and activation markers were determined on CD4 and CD8 T cells by flow cytometry. Cell-cycle analysis was performed by propidium iodide staining, and surface-marker expression was also assessed after culture of the T cells under conditions similar to those found in the synovial compartment. The majority of the T cells in the SF were CD45RO+CD45RBdull. There was greater expression of the activation markers CD69, HLA-DR, CD25 and CD71 on T cells from SF than on those from peripheral blood. Actively dividing cells accounted for less than 1% of the total T-cell population in SF. The presence or absence of IL-16 in T-cell cultures with SF or in a hypoxic environment did not affect the expression of markers of T-cell activation. T cells from the SF of patients with JIA were highly differentiated and expressed early and late markers of activation with little evidence of in situ proliferation. This observation refines and extends previous reports of the SF T-cell phenotype in JIA and may have important implications for our understanding of chronic inflammation

The effectiveness of a multidisciplinary foot care program for children and adolescents with juvenile idiopathic arthritis: an exploratory trial

Objectives: To evaluate the effectiveness of multidisciplinary foot-care, and to evaluate the methodological considerations of a trial of multidisciplinary care in juvenile idiopathic arthritis. Design: Exploratory randomised controlled trial. Subjects/Patients: Children/adolescents with juvenile idiopathic arthritis and inflammatory joint disease affecting the foot/ankle. Methods: Standard medical care was compared with a 12 month program of multidisciplinary foot-care informed by musculoskeletal ultrasound. This program was centred on strict disease control through rigorous examination and interventions delivered by a team comprised of a paediatric rheumatologist, podiatrist, physiotherapist and musculoskeletal ultrasonographer. Patients were assessed on foot impairment and disability scores using the Juvenile Arthritis Foot Disability Index. Results: Forty-four participants, aged 3-17 years were randomly assigned to receive the experimental (n = 21) or usual care (n = 23) interventions. There was an overall improvement in levels of foot related impairments in both groups over 12 months. Between-group differences in change scores for the Juvenile Arthritis Foot Disability Index were not statistically significant at 6 or 12 month follow-ups. Conclusion: The integrated multidisciplinary foot care interventions described in this trial were safe, but did not improve foot impairment levels relative to usual care. This trial identified several methodological challenges including recruitment/retention, difficulties with outcome tools and potential confounders.</p

Foot related impairments and disability in juvenile idiopathic arthritis persist despite modern day treatment paradigms

Background: Foot problems such as synovitis, growth disturbance and deformity are considered common in juvenile idiopathic arthritis (JIA) and have been previously reported in over 90% of cases. The medical management of JIA appears to have improved recently however little is known about the impact of new regimes on localised joints such as in the foot. This pilot study aimed to investigate the prevalence of foot related impairments and disability, and survey the medical and podiatric management of patients in a cohort of UK children with JIA. Methods: This study was a tertiary care based cross-sectional survey. Thirty consecutive JIA patients with a history of foot and ankle arthritis completed the juvenile arthritis foot disability index questionnaire (JAFI) (0-4 for each domain), child health assessment questionnaire (CHAQ) (0-3), and pain visual analogue scale (VAS) (0-100mm). Foot deformity score (0-38), active and limited joint counts (0-77) and walking speed (m/s) were measured also recorded. Foot care provision over the previous 12 months was determined from the medical records in 23/ 30 participants. Results were analysed using simple descriptive statistics and expressed as median (range). Results: Children received biologic agents in 35%, DMARDs in 65%, and 90% of participants had received multiple intra-articular cortico-steroid injections. Median (range) values for foot disease outcomes were JAFI impairment = 1 (0-3), JAFI activity limitation = 1 (0-4) JAFI participation restriction 1 (0-3), CHAQ = 0.38 (0-2), VAS pain = 22 (0-79), foot deformity = 6 (0-20), active joints = 0 (0-7), limited joints (0-31), walking speed = 1.09 (0.84- 1.38). The JAFI scores represent mild foot related impairment and disability. Gait defects, deformity or abnormal foot posture, and/or active foot disease were the main reasons for referral. 43% of children received specialist podiatry care comprising footwear advice, orthotic therapy, and silicone digital appliances together with intrinsic muscle strengthening exercises. Conclusions: Despite DMARD/biologic regimes and specialist podiatry, foot related impairment and disability persists in JIA children. Foot care appears to be in line with current recommendations. Further study is required to determine the long-term consequences of these changes found during childhood in the foot

An association between the acute phase response and patterns of antigen induced T cell proliferation in juvenile idiopathic arthritis

The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients: a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested; and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association between the acute phase response and the T cell population recruited to an inflammatory site

Agreement between proxy and adolescent assessment of disability, pain, and well-being in juvenile idiopathic arthritis.

OBJECTIVES: Adolescents with juvenile idiopathic arthritis have demonstrated substantial disagreement with their proxy's assessment of their disability, pain, and well-being. Our objective was to describe the clinical and psychological factors associated with discordance. STUDY DESIGN: This analysis included 204 proxy-adolescent (median age, 13 years) dyads that completed a Childhood Health Assessment Questionnaire for disability with 100-mm visual analogue scales for pain and well-being. Depressive symptoms in adolescents were measured by the Mood and Feelings Questionnaire and in proxies the General Health Questionnaire. Disagreement was assessed using Bland-Altman plots. Associations with discordance were identified using logistic regression analyses. RESULTS: There was higher agreement for disability (84%) than for pain (71%) and well-being (66%). Regression analyses found no association between age, sex, or disease duration and disagreement. However, relationships between disease activity and disagreement in outcomes were identified. Independent associations were found between increasing Mood and Feelings Questionnaire scores and disagreement in pain and well-being. CONCLUSIONS: Proxy and adolescent reports of pain and well-being are more likely to disagree in those with severe disease. Adolescents who report depressive symptoms are also more likely to disagree with their proxy. The reasons for these are multifactorial, and considerations of both reports are important when assessing outcomes in juvenile idiopathic arthritis