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Expression of the inflammatory chemokines CCL5, CCL3 and CXCL10 in juvenile idiopathic arthritis, and demonstration of CCL5 production by an atypical subset of CD8+ T cells
Daniel S Pharoah, Hemlata Varsani, Richard W Tatham, Katy R Newton, Wilco de Jager, Berent J Prakken, Nigel Klein, Lucy R Wedderburn
Arthritis Research & Therapy , 2006, DOI: 10.1186/ar1913
Abstract: The hyperplastic and highly vascular synovial tissue that characterises the synovitis of juvenile idiopathic arthritis (JIA) has a dense infiltrate of activated inflammatory T cells, as well as B cells, macrophages and dendritic cells [1-3]. To enter the inflamed site, these cells migrate across an endothelial barrier, a complex process that involves molecular interactions between several receptor-ligand pairs [4,5]. Chemokines are small secreted chemo-attractant molecules involved in such leukocyte trafficking, as well as playing important roles in lymphoid homeostasis and development [6-8]. Functionally distinct subsets of leukocytes express different chemokine receptors: thus, recently activated, effector and memory T cells express high levels of the receptors that bind inflammatory chemokines, thought to facilitate their accumulation at inflammatory sites, compared to na?ve cells. Similarly, chemokine receptor expression can be used to distinguish Th-1 T cells (which typically express CXCR3 and CCR5) from Th-2 populations (typically CCR3 positive) [9-11], or 'central' from 'effector' memory T cell populations [12].As well as mediating chemoattraction, chemokines may also play a direct role in the activation of leukocytes. For example, the chemokine CCL5 (also known as 'regulated upon activation, normally T cell expressed and secreted' (RANTES)) activates T cells when in high concentration through a tyrosine kinase pathway [13,14], leads to production of IFNγ by T cells [15] and may induce maturation of dendritic cells [16]. Thus, migration of T cells under a chemokine gradient into an inflamed site such as the joint in JIA may itself lead to further T cell activation. Furthermore, several of the inflammatory chemokines have recently been shown to be able to increase T cell activation during T cell-antigen presenting cell interaction through their recruitment to the immunological synapse [17].We have previously shown that inflammatory T cells in the joint in JIA
Atherosclerosis in Juvenile Idiopathic Arthritis  [PDF]
Ewa Jednacz,Lidia Rutkowska-Sak
Mediators of Inflammation , 2012, DOI: 10.1155/2012/714732
Abstract: Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE) or rheumatoid arthritis (RA). There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA). Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT) index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance. 1. Introduction Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process, in the form of ischaemic heart disease, disorders of cerebral circulation, or circulatory disorders of peripheral arteries occur in the adult population; however atherosclerotic changes have their beginning in childhood. The severity of atherosclerosis correlates with the number and intensity of risk factors such as body mass index (BMI), systolic and diastolic arterial blood pressure, total cholesterol, LDL, HDL, triglyceride concentrations, and passive and active cigarette smoking. At present, much significance is attached to the inflammatory aetiology of atherosclerosis, which makes it an inflammatory disease, a vascular wall response to injury. Proinflammatory cytokines, such as IL-1b, IL-6, IL-8, or TNF-α, play a significant role in the development and progression of atherosclerotic lesions. Elevation of the concentrations of acute phase proteins, such as CRP, is also a reflection of the inflammatory process. An elevated homocysteine concentration also increases the risk of developing cardiovascular diseases. Awareness of the fact that initiation of the atherosclerotic process takes place very early in life underscores the need for identifying these changes as early as
Dental and facial characteristics of patients with juvenile idiopathic arthritis
Savioli, Cynthia;Silva, Clovis A.A.;Lin, H. Ching;Campos, Lucia M.M.A.;Prado, Eliane F.B.G.;Siqueira, José Tadeu T.;
Revista do Hospital das Clínicas , 2004, DOI: 10.1590/S0041-87812004000300001
Abstract: objective: it has been shown that the temporomandibular joint is frequently affected by juvenile idiopathic arthritis, and this degenerative disease, which may occur during facial growth, results in severe mandibular dysfunction. however, there are no studies that correlate oral health (tooth decay and gingival diseases) and temporomandibular joint dysfunction in patients with juvenile idiopathic arthritis. the aim of this study is to evaluate the oral and facial characteristics of the patients with juvenile idiopathic arthritis treated in a large teaching hospital. method: thirty-six patients with juvenile idiopathic arthritis (26 female and 10 male) underwent a systematic clinical evaluation of their dental, oral, and facial structures (dmft index, plaque and gingival bleeding index, dental relationship, facial profile, and helkimo's index). the control group was composed of 13 healthy children. results: the mean age of the patients with juvenile idiopathic arthritis was 10.8 years; convex facial profile was present in 12 juvenile idiopathic arthritis patients, and class ii molar relation was present in 12 (p = .032). the indexes of plaque and gingival bleeding were significant in juvenile idiopathic arthritis patients with a higher number of superior limbs joints involved (p = .055). anterior open bite (5) and temporomandibular joint noise (8) were present in the juvenile idiopathic arthritis group. of the group in this sample, 94% (p = .017) had temporomandibular joint dysfunction, 80% had decreased mandibular opening (p = 0.0002), and mandibular mobility was severely impaired in 33% (p = .015). conclusion: this study confirms that patients with juvenile idiopathic arthritis a) have a high incidence of mandibular dysfunction that can be attributed to the direct effect of the disease in the temporomandibular joint and b) have a higher incidence of gingival disease that can be considered a secondary effect of juvenile idiopathic arthritis on oral health.
New Advances in Juvenile Idiopathic Arthritis  [PDF]
Jing-Long Huang
Chang Gung Medical Journal , 2012,
Abstract: Juvenile idiopathic arthritis (JIA) comprises a group ofheterogeneous disorders of chronic arthritis in childhood withno apparent etiology. Juvenile idiopathic arthritis is the mostcommon pediatric rheumatic disease and is associated withsignificant long-term morbidity and mortality. There have beenmajor advances in recent years in our understanding of thepathogenesis of JIA, the definition of disease control, and biological treatments for JIA. Multiple environmental and geneticfactors have been linked with the onset and / or the exacerbation of JIA, including perinatal factors, viral and bacterialinfections, epigenetic factors, and malnutrition. However, nosingle causative factor has been identified to date. As ourunderstanding of the complex network of immune cells andinflammatory cytokines has improved, biologics have beendeveloped to modulate the inflammatory processes. Indeed, anumber of such biologics have been demonstrated effective for the treatment of JIA.Although biologic agents may alleviate the inflammation associated with JIA and preventdisability caused by joint destruction, continued and comprehensive observation is requiredto determine the long-term outcomes associated with such treatment
Current Approach to Treatment of Juvenile Idiopathic Arthritis: Case Report of Hiperimmunglobulin E Syndrome Developed Juvenile Idiopathic Arthritis  [PDF]
Tuba Tülay Koca, Ayd?n Arslan
Open Journal of Rheumatology and Autoimmune Diseases (OJRA) , 2015, DOI: 10.4236/ojra.2015.53011
Abstract: Introduction: Juvenile idiopathic arthritis (JIA) represents a heterogeneous group of childhood chronic arthritic conditions. The pathogenesis of JIA remains incompletely understood. This disease can lead to a significant morbidity including joint deformity, growth impairment and a persistence of active arthritis into adulthood. The past two decades have witnessed significant advances in treatment and improved outcomes for affected children. With the current use of biologics, more target-specific, better tolerated, safer and more effective treatments have become possible. However, continuing, comprehensive follow-up is needed to characterize the long-term effects of such treatments. Hyperimmunoglobulin E syndrome (hyper-IgE, or Job’s syndrome) is a rare immune deficiency characterized by high IgE levels, atopic chronic eczema, tendency towards re-current pyogenic infection, neutrophil chemotaxis disorder and varying T-cell function impairment. Case Report: The case of a 17-year-old male patient with hyper-IgE who develops the oligoarticular subtype of JIA over a period of four years is discussed. The course of JIA is unfavorable, causing severe deformity of numerous joints (left elbow, right 3rd metacarpophalangeal, left knee, right ankle) and a fungal infection scar on the left eye. Blood tests show an ESR of 89 mm/h, rheumatoid factor (RF) 8.3 IU/mL (0 - 20) and positive antinuclear antibody (ANA). To improve gait, corrective surgery is performed on the right ankle, followed by rehabilitation and physical therapy. Conclusion: Developments in the near future will be crucial for understanding JIA pathophysiology and improving treatment.
Tocilizumab in the treatment of systemic juvenile idiopathic arthritis
Murakami M,Tomiita M,Nishimoto N
Open Access Rheumatology: Research and Reviews , 2012,
Abstract: Miho Murakami,1 Minako Tomiita,2,3 Norihiro Nishimoto11Laboratory of Immune Regulation, Wakayama Medical University, Wakayama, 2Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, 3Department of Allergy and Rheumatology, Chiba Children's Hospital, Chiba, JapanAbstract: Systemic juvenile idiopathic arthritis is one of the common rheumatic diseases in childhood and characterized by spiking fever, evanescent skin rash, lymphadenopathy, hepatosplenomegaly, and serositis, in addition to arthritis. Children with systemic juvenile idiopathic arthritis often show growth retardation and developmental abnormality, as well as macrophage activation syndrome, a life-threatening complication. Overproduction of interleukin-6 is pathologically responsible for the systemic inflammatory manifestations and abnormal laboratory results with systemic juvenile idiopathic arthritis. Thus, tocilizumab, a humanized antihuman interleukin-6 receptor antibody, has been developed as a therapeutic agent for the disease. A series of clinical studies have demonstrated the excellent efficacy and safety of tocilizumab for patients with active disease. Tocilizumab was approved for systemic juvenile idiopathic arthritis in Japan in 2008 and in the European Union and the United States in 2011.Keywords: systemic juvenile idiopathic arthritis, tocilizumab, antihuman interleukin-6 receptor antibody, biologics
Juvenile idiopathic arthritis and the temporomandibular joint
Y Mohammed, O Saeed
Alexandria Journal of Medicine , 2012,
Abstract: Background: The temporomandibular joint (TMJ) is one of the most underdiagnosed and undertreated conditions of juvenile idiopathic arthritis (JIA) because its involvement is often asymptomatic and the joint is difficult to examine. Objectives: The aim of this study was to investigate clinical as well as magnetic resonance imaging findings of temporomandibular joint inflammation among juvenile idiopathic arthritis patients and to detect the correlation between them, moreover with different disease parameters. Methods: Forty patients with JIA and 10 apparently healthy control subjects underwent clinical and post contrast magnetic resonance imaging (MRI) examinations for TMJs. MRI findings were scored. Clinical and laboratory disease parameters were recorded. Results: The clinical symptoms and signs of TMJ arthritis were detected in 35% and 62.5% of JIA cases, respectively. While TMJ disease was observed in 80% of patients using contrast enhanced MRI. The mean total MRI score was significantly higher in patients with active disease compared to those without activity. Patients with systemic and polyarticular JIA showed significant increase in the mean of synovial enhancement, effusion and total MRI scores compared to those with the oligoarticular type. MRI abnormalities revealed significant association with clinical signs of TMJ examination but not with symptoms. Synovial enhancement score showed significant positive correlation with disease activity score and C-reactive protein as a marker of inflammation. A significant positive correlation was found between total MRI score and disease activity, functional and pain scores in patients with JIA. Conclusions: TMJ arthritis is common among patients with JIA, therefore; examination of the TMJ is mandatory during the follow up of patients. Clinical signs of TMJ arthritis can be used as filter for MRI examination TMJ is an important joint which may be considered during categorizing JIA patients in different subtypes.
Impact of juvenile idiopathic arthritis on schooling
Ilham Bouaddi, Samira Rostom, Dalal El Badri, Asmae Hassani, Bouchra Chkirate, Bouchra Amine, Najia Hajjaj-Hassouni
BMC Pediatrics , 2013, DOI: 10.1186/1471-2431-13-2
Abstract: Thirty-three children with JIA were included in this study, having been previously diagnosed according to the classification criteria of the International League of Associations for Rheumatology (ILAR). Seventy-four healthy children were recruited to serve as controls. Data was obtained for all children on their school level, educational performance, and attendance. The rate of absenteeism due to health complications was noted.All healthy children were able to attend school (p<0.0001), while 33% of children with JIA were unable to attend school due to their condition. The students with JIA who were able to attend school were absent much more often than controls (63% compared to 20%), with a highly significant p value (p<0.0001). Slightly less than half of the JIA patients (48.5%) failed in their schooling. In univariate analysis, there was an association between absenteeism and tender joints (p=0.02), disease activity score (DAS28) (p=0.007), Childhood Health Assessment Questionnaire (CHAQ) (p=0.01), and erythrocyte sedimentation rate (ESR) (p=0.03). In multivariate analysis, the only association persisted between DAS28 and absenteeism.Our study suggested that the schooling of children with JIA was negatively impacted due to the disorder. More studies, with a larger sample of children, are needed to confirm our findings.Juvenile idiopathic arthritis (JIA) is the most common arthropathy of childhood, with an estimated prevalence between 7 and 400 for every 100,000 children [1]. It can persist over many years and can also lead to disability and dysfunction in adulthood [2]. JIA is a heterogeneous, multifactorial autoimmune disease characterized by persistent joint inflammation, which manifests as swelling, pain, and limitation of movement [3]. The disease can also lead to physical disability and reduced quality of life [4]. Different diseases affect school attendance to varying degrees, and there are indications that chronic arthritis is particularly disruptive becaus
Tocilizumab in the treatment of systemic juvenile idiopathic arthritis
Murakami M, Tomiita M, Nishimoto N
Open Access Rheumatology: Research and Reviews , 2012, DOI: http://dx.doi.org/10.2147/OARRR.S21969
Abstract: cilizumab in the treatment of systemic juvenile idiopathic arthritis Review (1635) Total Article Views Authors: Murakami M, Tomiita M, Nishimoto N Published Date July 2012 Volume 2012:4 Pages 71 - 79 DOI: http://dx.doi.org/10.2147/OARRR.S21969 Received: 11 February 2012 Accepted: 21 March 2012 Published: 05 July 2012 Miho Murakami,1 Minako Tomiita,2,3 Norihiro Nishimoto1 1Laboratory of Immune Regulation, Wakayama Medical University, Wakayama, 2Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, 3Department of Allergy and Rheumatology, Chiba Children's Hospital, Chiba, Japan Abstract: Systemic juvenile idiopathic arthritis is one of the common rheumatic diseases in childhood and characterized by spiking fever, evanescent skin rash, lymphadenopathy, hepatosplenomegaly, and serositis, in addition to arthritis. Children with systemic juvenile idiopathic arthritis often show growth retardation and developmental abnormality, as well as macrophage activation syndrome, a life-threatening complication. Overproduction of interleukin-6 is pathologically responsible for the systemic inflammatory manifestations and abnormal laboratory results with systemic juvenile idiopathic arthritis. Thus, tocilizumab, a humanized antihuman interleukin-6 receptor antibody, has been developed as a therapeutic agent for the disease. A series of clinical studies have demonstrated the excellent efficacy and safety of tocilizumab for patients with active disease. Tocilizumab was approved for systemic juvenile idiopathic arthritis in Japan in 2008 and in the European Union and the United States in 2011.
Mycobacterium tuberculosis monoarthritis in a child
Derek Rajakumar, Alan M Rosenberg
Pediatric Rheumatology , 2008, DOI: 10.1186/1546-0096-6-15
Abstract: One-third of the world's population is infected with Mycobacterium tuberculosis and the global burden of tuberculosis continues to grow [1,2]. Approximately one-quarter to one-third of children with tuberculosis develop extrapulmonary involvement [3-5]. Skeletal tuberculosis, now rare since the advent of antituberculosis therapy, occurs in approximately 5% of children with extrapulmonary tuberculosis [3,4]. The vertebral body is the most common skeletal site involved followed by lower limb bones [5,6]. Rarely, intra-articular inflammation can occur in children either as a result of direct invasion of the tuberculous bacillus into the joint or as a consequence of an aseptic reactive arthritis (so-called Poncet's disease) related to an extra-articular tuberculous focus [3-20]. Intra-articular Mycobacterium tuberculosis infection is especially rare in children in the absence of associated pulmonary disease [7,8,13,14,17,19]. Consequently, delays in recognition and treatment of this diagnostically challenging condition occur.We report a child with isolated Mycobacterium tuberculosis monoarthritis who presented with features initially suggesting oligoarthritis subtype of juvenile idiopathic arthritis (JIA). The patient we present illustrates the need to maintain heightened awareness that tuberculosis joint infection can occur in high-risk populations even in the absence of overt pulmonary involvement.At age 2 years 10 months this previously healthy North American Indian girl presented with a 3-week history of left knee swelling and morning stiffness without associated symptoms. There were no infectious contacts reported at first presentation. On initial physical examination, the left knee was moderately swollen and warm with signs of both intra-articular fluid and synovial hypertrophy. Flexion and extension were limited by 10 degrees. The child was afebrile and appeared otherwise healthy. There were no abnormal pulmonary signs and no peripheral lymphadenopathy. The remai
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