Juvenile Arthritis Patients Research Articles

Состояние медицинской помощи детям по профилю «ревматология» на примере юношеского артрита: взгляд пациентов и их родителей

The survey of parents is one of the optimal opportunities to understand the drawbacks of healthcare to children with rheumatic diseases, since these drawbacks are not reflected in patient medical records, statistical data, and the opinion of the doctor. Parents surveys provide information on the subjective understanding of the disease symptoms, duration and characteristics of the child's route from the disease onset to the diagnosis and treatment initiation, choice of primary care physician, problems on the route, disease awareness, and subjective understanding of the legal field regulating healthcare to children with rheumatic diseases. Objective. To identify possible ways to improve the access to healthcare among children with juvenile arthritis (JA) by analyzing the information from their parents on the patient portrait, patient pathway, social burden of the disease, its impact on various aspects of the life of a child and the family, and legal field regulating healthcare to children with rheumatic diseases. Patients and methods. We conducted a cross-sectional study where we surveyed 306 parents of JA patients, including 56 children with JA with systemic onset, 230 with different JA variants without systemic manifestations, and 20 with an unspecified JA. The main parameters assessed were as follows: JA patient portrait, patient pathway, social burden of JA, parental awareness about the and legal field regulating healthcare to children with rheumatic diseases. We used Fisher's exact test and Pearson's χ2-test to assess the significance of differences. All the p-values given are based on two-sided tests. Differences were considered significant at р < 0.05. Results. According to parents, the most common clinical symptoms of JA without systemic manifestations at onset were restricted movements of joints (74.3%), arthralgia (71.7%), morning stiffness (62.2%); JA patients with a systemic onset had fever (78.5%) and rash (68%). Three-quarters of respondents (regardless of the JA type) visited a pediatrician within the first month after symptom onset. Only 52% of patients were referred for consultation to a pediatric rheumatologist within a month after symptom onset. More than one-third of patients were diagnosed with JA within a month; half of the patients, after 1–6 months; and 18% of patients, after 6 months. The majority of children (88%) started to receive biologicals later than 6 months after the diagnosis; 64% of JA patients with a systemic onset and 92% of JA patients without systemic manifestations. The disease negatively affected everyday life of the child and his/her family in 91% of cases. Sixty-one percent of respondents knew about the existence of clinical guidelines; 44% of them knew about the right to have the status of a “disabled child” without subsequent re-examination before the age of 18; 39% of respondents knew about the possibility to have the status of a “disabled child” in those children whose remission depends on the constant use of biologicals and/or immunosuppressant; 17% of parents knew about the possibility to use remote monitoring tools. Conclusion. The opinion of parents is an important information about the quality of healthcare to children with rheumatic diseases. It should be considered when developing measures to optimize medical care for such children. Our data on the portrait and pathway of the patient should be used to determine the target group of specialists, whose better awareness of rheumatic diseases will reduce the time to diagnosis and treatment initiation. The opinion about the social burden of the disease and the subjective understanding of the legal field regulating healthcare to children with rheumatic diseases will provide a rationale for developing new measures of social, psychological, and legal support, including the creation of "Schools for patients with rheumatic diseases." Kew words: disease awareness, healthcare organization, patient portrait, patient pathway, legal field, social burden of the disease, juvenile arthritis

Identifying Research Priorities among Patients and Families of Children with Rheumatic Diseases Living in the United States.

To improve the quality and participation in pediatric rheumatology research, patient-prioritized studies should be emphasized. We collaborated with United States-based pediatric rheumatology advocacy organizations to survey patients and caregivers of children with rheumatic diseases to identify what research topics were most important to them. We conducted Web-based surveys and focus groups (FG) of patients and caregivers of children with juvenile myositis (JM), juvenile arthritis (JA), and childhood-onset systemic lupus erythematosus (cSLE). Surveys were emailed to listservs and posted to social media sites of JM, JA, and cSLE patient advocacy organizations. An initial survey asked open-ended questions about patient/caregiver research preferences. Responses were further characterized through FG. A final ranking survey asked respondents to rank from a list of research themes the 7 most important to them. There were 365 JM respondents, 44 JA respondents, and 32 cSLE respondents to the final ranking survey. The top research priority for JM was finding new treatments, and for JA and cSLE, the priority was understanding genetic/environmental etiology. The 3 prioritized research themes common across all disease groups were medication side effects, disease flare, and disease etiology. Patient-centered research prioritization is recognized as valuable in conducting high-quality research, yet there is a paucity of data describing patient/family preferences, especially in pediatrics. We used multimodal methodologies to assess current patient/caregiver research priorities to help frame the agenda for the pediatric rheumatology research community. Patients and caregivers from all surveyed disease groups prioritized the study of medication side effects, disease flares, and disease etiology.

Juvenile Arthritis Patients Suffering from Chronic Inflammation Have Increased Activity of Both IDO and GTP-CH1 Pathways But Decreased BH4 Efficacy: Implications for Well-Being, Including Fatigue, Cognitive Impairment, Anxiety, and Depression.

Juvenile idiopathic arthritis (JIA) represents joint inflammation with an unknown cause that starts before the age of 16, resulting in stiff and painful joints. In addition, JIA patients often report symptoms of sickness behavior. Recent animal studies suggest that proinflammatory cytokines produce sickness behavior by increasing the activity of indoleamine-2,3-dioxygenase (IDO) and guanosinetriphosphate–cyclohydrolase-1 (GTP–CH1). Here, it is hypothesized that inflammation in JIA patients enhances the enzymatic activity of IDO and GTP-CH1 and decreases the co-factor tetrahydrobiopterin (BH4). These compounds play a crucial role in the synthesis and metabolism of neurotransmitters. The aim of our study was to reveal whether inflammation affects both the GTP-CH1 and IDO pathway in JIA patients. Serum samples were collected from twenty-four JIA patients. In these samples, the concentrations of tryptophan (TRP), kynurenine (KYN), tyrosine (TYR), neopterin, and phenylalanine (PHE) were measured. An HPLC method with electrochemical detection was developed to quantify tryptophan, kynurenine, and tyrosine. Neopterin and phenylalanine were quantified by ELISA. The KYN/TRP ratio was measured as an index of IDO activity, while the PHE/TYR ratio was measured as an index of BH4 activity. Neopterin concentrations were used as an indirect measure of GTP-CH1 activity. JIA patients with high disease activity showed higher levels of both neopterin and kynurenine, and a higher ratio of both KYN/TRP and PHE/TYR and lower tryptophan levels than clinically inactive patients. Altogether, these data support our hypothesis that inflammation increases the enzymatic activity of both IDO and GTP-CH1 but decreases the efficacy of the co-factor BH4. In the future, animal studies are needed to investigate whether inflammation-induced changes in these enzymatic pathways and co-factor BH4 lower the levels of the brain neurotransmitters glutamate, noradrenaline, dopamine, serotonin, and melatonin, and consequently, whether they may affect fatigue, cognition, anxiety, and depression. Understanding of these complex neuroimmune interactions provides new possibilities for Pharma-Food interventions to improve the quality of life of patients suffering from chronic inflammation.

Cell-bound complement activation products (CB-CAPs) have high sensitivity and specificity in pediatric-onset systemic lupus erythematosus and correlate with disease activity.

Elevated levels of cell-bound complement activation products (CB-CAPs) (C4d deposition on B lymphocytes (BC4d) and/or erythrocytes (EC4d)) are sensitive and specific in diagnosis and monitoring of adult systemic lupus erythematosus (SLE). Our objective was to evaluate the role of CB-CAPs for diagnosis and monitoring of pediatric-onset SLE (pSLE). A prospective cohort study of 28 pSLE and 22 juvenile arthritis patients was conducted. SLE disease activity was determined using a clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) that excluded serologies. Autoantibodies were measured using solid-phase immunoassays, C3 and C4 using immunoturbidimetry, and CB-CAPs using quantitative flow cytometry. Abnormal CB-CAPs were defined as EC4d or BC4d above the 99th percentile for healthy adults (>14 and > 60 net mean fluorescence intensity (MFI), respectively). Performance characteristics of CB-CAPs were assessed using area under the curve (AUC) for receiver operating characteristics. Linear mixed effect models evaluated the correlation between CB-CAPs and clinical SLEDAI over 6 months. BC4d yielded higher AUC (0.91 ± 0.04) than C3 (0.63 ± 0.08) and C4 (0.67 ± 0.08) ( p < 0.05). Abnormal CB-CAPs were 78% sensitive and 86% specific for diagnosis of pSLE (Youden's index = 0.64 ± 0.11). In contrast to BC4d, EC4d levels correlated with clinical SLEDAI ( p < 0.01). CB-CAPs (EC4d and BC4d) have higher sensitivity and specificity than low complement in pSLE, and may help with diagnosis of pSLE. EC4d could provide a useful biomarker for disease activity monitoring.

The management of lupus in young people.

Juvenile onset systemic lupus erythematosus (JSLE) accounts for 20% of all SLE presentations. It most commonly develops around adolescence. It is a serious and complex autoimmune disease that, although requiring specialist care, will benefit from the active involvement of general practice. JSLE is a chronic autoimmune disease that can affect any part of the body including skin, joints, and the major organs. It most commonly presents around adolescence (median age at diagnosis 12–14 years). The female preponderance is less marked in adolescents than in adults.1 JSLE patients have a more aggressive disease than adults. They have higher rates of organ involvement including renal and liver disease, are more likely to die in the acute phase of the illness, and sustain more organ damage. In contrast with some juvenile arthritis patients, JSLE patients do not ‘grow out’ of the disease. They will therefore have a lengthy disease duration and incur a great burden of medication and its unwanted effects. JSLE patients are still about 18 times more likely to die than their peers (standardised mortality rate [SMR] JSLE 18.3, confidence interval [CI] = 11.8 to 28.3), in contrast with adults (SMR 3.1, CI = 2.6 to 3.9).1 Deaths usually relate to active JSLE with organ involvement, often in the context of suboptimal treatment adherence. Counselling patients with organ involvement about the controllable but serious nature of the illness is difficult but essential. JSLE symptoms are highly variable from a relatively mild disease such as a rash with joint pains and fatigue, to a …

3D evaluation of mandibular skeletal changes in juvenile arthritis patients treated with a distraction splint: A retrospective follow-up.

To evaluate three-dimensional (3D) condylar and mandibular growth in patients with juvenile idiopathic arthritis (JIA) with unilateral temporomandibular joint involvement treated with a distraction splint. Cone-beam computed tomography (CBCT) scans were taken for 16 patients with JIA with unilateral TMJ involvement before treatment (T0) and 2 years after treatment (T1). All patients received orthopedic treatment with a distraction splint. Eleven patients without JIA who were undergoing orthodontic treatment without a functional appliance or Class II mechanics and who had taken CBCT scans before and after treatment, served as controls. Reconstructed 3D models of the mandibles at T0 and T1 were superimposed on stable structures. Intra- and intergroup growth differences in condylar and mandibular ramus modifications and growth vector direction of the mandibular ramus were evaluated. In all patients with JIA there were asymmetric condylar volume, distal and vertical condylar displacement, and ramus length differences that were smaller on the affected side. Condylar displacement was more distal and less vertical in the JIA group than in the control group. A larger distal growth of the condylar head and a more medial rotation of the ramus on the affected side were found in the JIA group. The orthopedic functional treatment for patients with JIA allows for condylar adaptation and modeling, thereby hindering, although with a widely variable response, a further worsening of the asymmetry. Unilateral affection has a possible influence on the growth of the nonaffected side.

Association of health-related quality of life in childhood-onset systemic lupus erythematosus with ethnicity: results from a multiethnic multicenter Canadian cohort.

To evaluate the influence of ethnicity on self-reported health-related quality of life (HRQOL) in the Canadian childhood-onset systemic lupus erythematosus (cSLE) population. Patients with cSLE at 4 pediatric centers were consecutively enrolled. Sociodemographics and multiple disease activity measures were collected. The Child Health Questionnaire (CHQ) was administered and analyzed by ethnicity. We enrolled 213 cSLE patients, and complete data from 196 patients with the following ethnicities were analyzed: white (33%), Asian (32%), South Asian (16%), African American (11%), Latino/Hispanic (5%), and Aboriginal (4%). Compared to healthy children, cSLE patients rated their HRQOL significantly more poorly in 9 of 10 individual domains, and in 4 of 10 domains when compared to a cohort of juvenile arthritis patients. Within the cSLE cohort, CHQ scores were lower in 5 of 10 domains in white patients versus nonwhite ethnicities (P < 0.05 for each). Physical summary scores were lower for white patients compared to the other ethnicities aggregated together (mean ± SD 46.0 ± 11.9 versus 50.4 ± 10.1; P = 0.009); however, psychosocial summary scores were similar among the groups (mean ± SD 40.5 ± 14.6 versus 42.8 ± 12.7; P = 0.26). Disease activity measures, including the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus Activity Measure, Revised, and physician global visual analog scale, were similar across ethnicities. However, patient-reported Systemic Lupus Erythematosus Activity Questionnaire symptom scores were greater in patients of white ethnicity compared to those of Asian ethnicity (mean ± SD 8.2 ± 5.8 versus 4.5 ± 4.7; P = 0.004). The self- and parent-reported health status of Canadian cSLE patients differed across ethnicities, with white patients reporting lower HRQOL despite similar and overall low disease activity.

Stressful Life Events Antedating Chronic Childhood Arthritis

To investigate associations between antecedent stressful life events and occurrence of juvenile arthritis (JA). The study population comprised patients with JA referred to a pediatric rheumatology clinic between 1981 and 2010. A questionnaire, which was developed as a screening tool by the clinic, was completed at the first clinic visit by patients' parents and, for comparison, by parents of unrelated age, sex, geographically, and temporally matched healthy controls. The entire questionnaire captured a broad array of clinical, demographic, psychosocial, and environmental data, including questions about stressful life events from 686 patients with JA and from 1042 controls. Patients were more likely to have experienced a serious upset (OR 4.81; p < 0.0001), a currently ill family member (OR 2.29; p < 0.0001), separated parents (OR 1.96; p < 0.0001), or difficulties with interpersonal relationships (OR 2.54; p < 0.0001) prior to first clinic presentation compared to controls. Children with oligoarticular JA were more likely than controls to have experienced a serious upset (OR 3.46; p = 0.008), an ill family member (OR 3.79; CI 2.02, 7.11; p < 0.0001), or problems with interpersonal interactions (OR 3.32; p < 0.0001). Children with polyarticular JA were more likely to have experienced a serious upset (OR 5.68; p < 0.0001), separated parents (OR 2.66; p = 0.001), a deceased parent (OR 6.75, p = 0.017), or problems with interpersonal relationships (OR 2.39; p = 0.009). No significant differences were observed when comparing systemic JA patients to controls. Strong associations between stressful life events antedating the first clinic visit of patients with JA indicate that life event stresses should be identified and addressed when first encountering and managing children with JA.

Risk of significant cytopenias after treatment with tocilizumab in systemic juvenile arthritis patients with a history of macrophage activation syndrome

Tocilizumab (TCZ) is the first FDA- approved treatment for systemic juvenile idiopathic arthritis (sJIA). We report 3 cases of cytopenias in children with sJIA treated with TCZ. Two of the children who developed significant cytopenias shortly after initiation of TCZ had a history of macrophage activation syndrome. We raise the possibility that patients with a tendency towards MAS have an increased risk of developing cytopenias when treated with tocilizumab.

Juvenile Arthritis Patients Report Favorable Subjective Outcomes of Hip Arthroplasty Despite Poor Standard Outcome Scores

We evaluated midterm patient-reported outcomes and satisfaction with total hip arthroplasty in patients who had severe juvenile idiopathic arthritis. Thirty-one patients (49 hips), with a mean age of 29 years (range, 16-43 years), reported low hip pain and stiffness at follow-up (mean, 7 years; range, 3-17 years). Up to 92% were satisfied with their ability to perform various activities; 96% were satisfied with pain relief. A mean postoperative flexion arc of 96° was observed. Final 36-Item Short Form Health Survey, EuroQol in 5 dimensions, Western Ontario and McMaster Universities Arthritis Index, and Harris Hip scores were lower than reference populations, particularly for mobility, physical functioning, and social functioning subscores. Young adults with end-stage hip involvement and severe longstanding juvenile idiopathic arthritis expressed high satisfaction with total hip arthroplasty, which improved range of motion, pain, and stiffness, despite poor performance on widely used outcome measures.

Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays

IntroductionJuvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients.MethodsA pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs.ResultsQuantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis.ConclusionThe NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.

THE CLINICAL AND DIAGNOSTIC VALUE OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN EARLY JUVENILEARTHRITIS

Objective: to estimate the concentration of anti-cyclic citrullinated peptide antibodies (CCPA), the frequency of their increase, and their diagnostic value in children with early juvenile arthritis (JA). Subjects and methods. Sera from 80 patients (36 girls and 44 boys) aged 1,5 to 16 years (mean age 8,5+5,03 years) who had early JA were tested for CCPA. The diagnosis of juvenile rheumatoid arthritis (JRA) and juvenile chronic arthritis (JCA) was made in 19 and 57 patients, respectively; the duration of JA being &lt; 3 months in 4. The systemic type of JA was present in 8 (10%) children; the polyarticular and oligoar-ticular types in 37 (46,2%) and 35 (43,8%) children, respectively. The duration of the disease in all children did not exceed 6 months. A comparison group comprised 54 adult patients with early rheumatoid arthritis (RA), 27 with undifferentiated arthritis (UDA), and 37 apparently healthy children. The concentration of CCPA was measured by immunoassay using the commercial оAxis Shield Diagnosticsп kits (United Kingdom), the upper normal range being 5 U/ml. Results. The higher levels of CCPA were revealed in 7 (8,8%) children with early JA. Their frequency was higher than that in healthy children; however, it was lower than that in adult patients with RA and comparable with UDA. CCPAs were detected more frequently in JCA and rheumatoid factor (RF)-positive patients. Higher concentrations were observed in patients with RF-positive polyarticular JA. There were correlations of CCPA with the number of swollen and tender joints, RF. Conclusion. In patients with early JA, the detection rate of CCPA is significantly higher than that in healthy children and comparable with that of RF. CCPAs have a high specificity for the diagnosis of JRA (an independent nosological entity within JA) are a risk factor of polyarthritis. The early detection of CCPA alone or in combination with RF in JA patients may serve the basis for the early use of active, frequently aggressive therapy.

Anakinra for Systemic Juvenile Arthritis

Poor outcomes in systemic juvenile arthritis have been associated with persistent thrombocytosis, increased sedimentation rates, anemia, polyarthritis, and prolonged steroid use. Off-label treatment with recombinant interleukin-1 receptor antagonist therapy (anakinra) has become more common since reports of its association with reduced systemic symptoms and arthritis scores, improved laboratory parameters of inflammation, and decreased corticosteroid requirements. To examine the efficacy and safety of anakinra in a regional cohort of systemic juvenile arthritis patients. We performed a retrospective case series of systemic juvenile arthritis patients (n = 33) treated with anakinra at 3 Pediatric Rheumatology centers. The effect of anakinra on corticosteroid dose, sedimentation rate, platelet count, albumin, hemoglobin, arthritis joint counts, and height Z score was determined using the paired t test. We evaluated differences in change in these variables between patient groups within the sample determined by: age of onset, anakinra dose, and duration from diagnosis until anakinra treatment. Treatment was associated with decreases in corticosteroid dosage and sedimentation rate and increases in hemoglobin and albumin (P < 0.02). There were decreases in large joint arthritis counts (P < 0.04) but not small joint counts after 3 to 4 months. There were greater decreases in sedimentation rates from pre to post (1-2 months) in patients on high versus low dose anakinra (P < 0.001). Fever and rash, present in 7 cases before treatment, was resolved. Eight patients had periods of arthritis, 1 developed macrophage activation syndrome, and another Epstein Barr virus. Over half of patients reported localized pain or swelling at their injection site. Treatment with anakinra was associated with short-term improvements in large joint counts and laboratory parameters of active disease. Higher anakinra doses may be more efficacious in treating the systemic inflammatory response in systemic onset juvenile idiopathic arthritis patients. A subset of patients had periods of arthritis during treatment, and local side-effects were frequent. Our experience supports the continued use of interleukin-1 inhibition in systemic juvenile arthritis and the search for more effective and more tolerable forms of interleukin-1 inhibition.

The mark of T reg cells

Regulatory T (T reg) cells found in the synovial fluid of inflamed joints can be identified by the coexpression of CD4, CD25, and CD27, according to Ruprecht and colleagues on page 1793. Suppression of damaging T cell responses by CD4+ T reg cells is critical for the prevention of autoimmune disease. But studying these cells in the context of disease has been problematic, largely because CD4+ T reg cells and activated CD4+ T cells express many of the same surface molecules and are thus difficult to distinguish. Although coexpression of CD4 and the high affinity interleukin (IL)-2 receptor (CD25) identifies T reg cells in the circulation, CD25 cannot distinguish between T reg cells and local effector T cells, which up-regulate this molecule upon activation. Figure CD4+ regulatory T cells in the synovial tissues of a juvenile arthritis patient coexpress CD25 (red) and CD27 (green). Ruprecht et al. now show that CD4+ CD25+ T reg cells found in the inflamed joints of children with autoimmune arthritis can be distinguished from their CD4+CD25+ effector T cell counterparts by the expression of the TNF receptor family member CD27—a molecule that is down-regulated on activated T cells. CD27 expression identified T reg cells in these patients, as the ability to suppress T cell proliferation in vitro resided solely in the CD4+CD25+CD27+ T cell subset. But why does an autoimmune response develop in these patients despite an abundance of T reg cells at the site of disease? The authors suggest that the cytokines IL-7 and IL-15, which were detected in the patients' synovial fluid, might be to blame, as the combination of these cytokines reversed the in vitro ability of the T reg cells to inhibit T cell proliferation.

Reduction of Soluble Complement Receptor 2/CD21 in Systemic Lupus Erythomatosus and Sjögren's Syndrome but not Juvenile Arthritis

A soluble form of the complement receptor CD21 (sCD21) is shed from the lymphocyte surface. The amount of sCD21 in serum may modulate immunity as sCD21 levels are correlated with several clinical conditions. We report here the serum levels of sCD21 in juvenile arthritis (JA), systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). Using enzyme-linked immunosorbent assay, we determined sCD21 levels in SLE, SS and JA patients. Mann-Whitney test for nonparametric two-tail P value was performed to obtain statistical significance. Cytometrical analysis of synovial fluid leucocytes of JA patients was done on a FACSsort. While sCD21 levels in SLE and SS are reduced to levels previously found in rheumatoid arthritis (RA), JA sCD21 levels were normal. sCD21 levels did not correlate with clinical parameters and immunophenotype of synovial cells. CD4 T cells in the synovium were almost all of the CD45RO memory type and 13 of 40 patients displayed synovial expansion of gammadeltaT cells. CD21 shedding in JA differs from RA/SS/SLE. JA sCD21 levels in synovial fluid are always lower compared to blood levels of the same patients. Analysis of JA synovial T cells indicates a T-cell driven response.

Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype.

The aim of the present study was to investigate the patterns of cytokine production by T cell clones raised from in vivo activated synovial fluid (SF) mononuclear cells (MNC) of five patients with oligoarticular juvenile arthritis (JA). Freshly isolated SF T cells were cultured in vitro with low dose recombinant IL-2 and subsequently cloned by limiting dilution. Sixty-four clones were obtained from the five patients studied. Fifty-nine clones were TCR alpha/beta+, either CD4+ (n = 43) or CD8+ (n = 15). The remaining five clones were TCR gamma/delta+, CD4-, CD8-. Clone immunophenotypes differed in the individual patients. Forty-four T cell clones were stimulated with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) and supernatants tested for the presence of IL-2, IL-4, IL-5 and interferon-gamma (IFN-gamma) by ELISA or bioassays. Cytokine mRNA accumulation was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). Most of 44 clones tested released large amounts of IFN-gamma irrespective of the immunophenotype. Of these, 27 were classified as Th1-type and 17 as Th0-type based upon the IFN-gamma/IL-4 ratio in culture supernatants. Finally, when 10 representative T cell clones were tested for pro- and anti-inflammatory cytokines, gene expression by RT-PCR, all of them were found to express the granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha), IL-10 and transforming growth factor-beta 1 (TGF-beta1) genes, and half of them IL-6 and IL-8 mRNA. In conclusion, T cell clones, that represent the progeny of in vivo activated SF T cells from oligoarticular JA patients, display heterogeneous immunophenotypes, but all share the ability to produce large amounts of IFN-gamma, with a predominant Th1/Th0 pattern. The expression of pro- and anti-inflammatory cytokine genes in these clones suggests that in vivo activated SF T cells modulate joint inflammation in a complex fashion.

A Danish adaptation of the Pain Coping Questionnaire for children: preliminary data concerning reliability and validity

The aim of this study was to determine the reliability and validity of a Danish translation of the Pain Coping Questionnaire (PCQ) for children in Danish children. The PCQ was translated using a translation‐back‐translation method. The subjects were 352 healthy children and 40 children with juvenile arthritis (JA), aged 8–17 y. Sixteen of the JA children were divided into a high‐pain group (n= 7) and a low‐pain group (n= 9). The results were factor analysed using principal component analysis with varimax rotation. Clinical pain intensity was measured using visual analogue scales (VAS) from the Varni/Thompson Pediatric Pain Questionnaire. Experimental pain was induced using a cold pressor pain paradigm and outcome measures were pain intensity, pain discomfort and tolerance to cold pressor pain. A seven‐factor solution emerged as the most consistent factor structure. Four subscales, Seeking Social Support (SSS), Cognitive Distraction (CD), Externalizing (EXT) and Internalizing/Catastrophizing (INT), corresponded with the parallel subscales proposed by Reid et al. (Pain 1998; 76: 83–96). Two subscales, Positive Self‐Statements (PSS) and Behavioral Distraction (BD), were composed of four of the five items from the previously proposed subscales. One subscale, Information Seeking/Problem Solving (IP), consisted of items from two subscales proposed by Reid et al., i.e. Information Seeking and Problem Solving. Internal consistencies of the subscales were acceptable, with reliability coefficients ranging from 0.60 (BD) to 0.83 (IP) and with test‐retest reliabilities between 0.59 and 0.78. Low‐pain JA patients showed significantly higher levels of BD than High‐pain JA patients (p &lt; 0.05). Greater utilization of PSS and BD was associated with less patient‐reported present pain and less average everyday pain (p &lt; 0.05‐0.01), and greater utilization of INT was significantly associated with higher experimental pain intensity (p &lt; 0.01). These preliminary findings provide support for the reliability and validity of the Danish modification of the PCQ in a Danish population and for the hypothesis that paediatric pain‐coping strategies are associated with the intensity of clinical and experimental pain.

Cold Pressor Pain: Comparing Responses of Juvenile Arthritis Patients and Their Parents

The objective of this study was to compare the reactions to experimental cold pressor pain of Juvenile Arthritis (JA) patients, healthy children, and their parents. Methods. We compared pain threshold, discomfort, intensity, and tolerance to experimental cold pressor pain in 15 JA patients (age 9–15) and one of their parents and a control group of 25 healthy children (age 9–12) and one of their parents. Results: JA-patients exhibited significantly lower mean pain tolerance than healthy children. Pain tolerance correlated significantly with disease duration. Parents of JA-patients showed significantly greater mean pain intensity than parents of healthy children, and had higher estimates of their child's ability to endure pain than parents of healthy children. Correlations were found between pain scores of children and their parents for both pain intensity and tolerance. The pain coping category of Catastrophizing was associated with several of the experimental pain response measures. Conclusion. The results suggest that J A patients may differ from healthy children with regard to their responses to experimental pain, and that pain responses of both JA patients and healthy children could be related to the pain response of their parents.

Antihistone antibodies in antinuclear antibody—positive juvenile Arthritis

The binding of antinuclear antibody-positive juvenile arthritis (JA) sera to bovine thymus histones H1, H2A, H2B, H3, and H4 was studied by an enzyme-linked immunosorbent assay. Seventy-five percent of the JA patients tested positive for at least 1 antibody specificity. Antihistone antibodies were predominantly IgM, while IgG antibodies were less common and were restricted to histones H1 or H3. In the group of patients with JA of pauciarticular onset, antihistone antibodies were significantly more elevated in patients with past or present uveitis than in patients without a history of uveitis. Anti-H1 antibodies in JA patients were found to react mostly with determinants located in the carboxyl-terminal domain of the H1 molecule. Sera were also reactive with human histone H1(0) or chicken histone H5, which are H1 variants found only in nondividing cells.

Antibody Reactivity against Single Stranded DNA of Various Species in Normal Children and in Children with Diffuse Connective Tissue Diseases

The aim of this work was to study possible differences in the humoral response against autologous and heterologous (bacterial and mammalian) ssDNA in children with diffuse connective tissue diseases (DCTD) compared with age matched controls. We found that IgM anti ssDNA were significantly increased in systemic lupus eritematosus (SLE) and in juvenile arthritis (JA), but not in juvenile dermatomyositis (JDM). IgG anti ssDNA were significantly elevated only in children with SLE. We next evaluated the binding specificity to human and bacterial ssDNA by inhibition assays. We found that SLE and JA sera recognised epitopes shared in common to endogenous and bacterial ssDNA. In contrast, in normal subjects IgG binding to bacterial DNA was not inhibited by human DNA, while IgG anti human ssDNA were cross reactive with the bacterial antigen. These data suggest that natural antibodies (IgM) producing cells are activated in some but not all DCTD, and that normal children have different reactivity against autologous and heterologous ssDNA with respect to SLE and JA patients.