Top PDF Genetics in juvenile idiopathic arthritis

Genetics in juvenile idiopathic arthritis

Genetics in juvenile idiopathic arthritis

Demographic and clinical data, together with detailed information about the use of MTX and co-medication were collected from the patients’ chart. At the time point of start and at 6 months after initiation of MTX, the following parameters were scored: the physician’s global assessment of disease activity, the amount of joints with arthritis (defined by swelling, not due to bony enlargement, or if no swelling is present, limita- tion of motion accompanied either by pain on motion and/or tenderness) (32 joint count) and the erythrocyte sedimentation rate (ESR). The physician’ global assessment was scored at a five point scale (1 no, 2 mild, 3 moderate, 4 severe and 5 very severe activity). In addition, the joint score was divided into categories with 0 no arthritis, 1 monoarthritis (1 joint), 2 oligoarthritis (2-4 joints), 3 polyarthritis (5-10 joints), 4 severe polyarthritis (>11 joints) and in systemic JIA patients an additional category (5) was used when systemic features were present.
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Genetic epidemiology: Juvenile idiopathic arthritis genetics   What's new? What's next?

Genetic epidemiology: Juvenile idiopathic arthritis genetics What's new? What's next?

JIA is thought to be an autoimmune condition (or possibly group of conditions) in which the immune response to self-antigen, present within the inflamed joint, plays a central role. But what is the nature of this antigen? Since several well-described HLA associations are known for juvenile arthritis it has been tempting to try to extrapolate from these to suggest the initiating pathogenic organism(s). Albani [29] has shown that the Escherichia coli heat shock protein DNAJ specifically binds within the groove of HLA class II alleles known to be associated with pauciarticular juvenile chronic arthritis. Subsequently, work with synthetic peptides from E. coli DNAJ suggested that T-lymphocyte reactivity may be critical to T-cell regula- tory mechanisms that affect the course of joint inflamma- tion in oligoarticular-JIA patients [30]. In an allied approach Kamphuis et al. [31] generated putative self-epi- topes in silico from the rat model of adjuvant arthritis. A selection of human analogues of the recognized peptides in adjuvant arthritis were made and tested for T-cell recog- nition in JIA patients, by measuring proliferative activity of peripheral blood mononuclear cells. Four of the selected peptides were recognised by 20–40% of JIA patients. Amongst these were peptides from matrix metallopro- teinases, and also from proteoglycan/aggregan molecules. Such an approach has implications for the better identifi- cation of autoreactive T cells involved in JIA and the initiat- ing micro-organisms that may be involved.
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A comprehensive review of the genetics of juvenile idiopathic arthritis

A comprehensive review of the genetics of juvenile idiopathic arthritis

Interpreting the different associations (or lack of associa- tions) between genetic variants and phenotypes can be further complicated by differences in phenotype descrip- tion. JIA comprises several sub-phenotypes with distinct clinical features and outcomes[48]. Although the ILAR classification criteria, which are increasingly being used to describe juvenile arthritis attempts to define homogenous subtypes, there are still some challenges. For instance a child with four affected joints is classified as oligoarticular JIA, while a child with five affected joints is classified as polyarticular JIA, although clinically the difference is not significant. Similarly, a child with five affected joints and another with over 20 joints are both classified as polyar- ticular, although clinically they appear distinct. While this can be addressed in part, by analyzing children with JIA as a group, and then performing analyses by subtypes, this results in multiple comparisons. One approach to address this issue might be to use genetic information to stratify subjects into subtypes, and this might results in more homogenous subtypes. For instance studies of adult RA subjects frequently stratify the subjects based on presence or absence of the shared HLA-DR epitope[49,50]. Simi- larly, it might be reasonable to stratify JIA patients by HLA associations while conducting genetic studies. It also would better facilitate comparisons of genetic studies per- formed in different populations. Finally, this would also help to delineate associations due to LD. For instance the MHC region has extensive LD, and associations described with variants in this region could be due to LD with HLA polymorphisms. Together, these observations reinforce the need for meticulous attention to defining the pheno- types and caution with interpreting results of genetic asso- ciation studies.
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Outcome of Juvenile Idiopathic Arthritis-Enthesitis related Arthritis.

Outcome of Juvenile Idiopathic Arthritis-Enthesitis related Arthritis.

Despite significant advances in genetics and molecular immunology, understanding of the etiology of JIA is piecemeal. Genetic factors and environmental triggers are thought to play a part ultimately leading to abnormalities in the cellular, humoral, and innate arms of the immune system. 18,19,20 The evidence for a genetic contribution to JIA comes from several sources. Twin studies show a high concordance of disease in monozygotic twins. A study of 164 affected sibling pairs with JIA showed a 70% concordance for gender, 73% for disease onset, and 66% for disease course, considerably higher than in a non–affected sibling pair cohort.First-degree relatives of children with JIA have a higher rate of autoimmune disease than controls. Genetic influences on JIA susceptibility and phenotype are polygenic,and a more recent genome-wide scan in JIA affected sibling pair families has supported the idea that multiple genetic loci contribute to JIA susceptibility.
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The human microbiome and juvenile idiopathic arthritis

The human microbiome and juvenile idiopathic arthritis

A number of important questions remain outstanding. For instance, it is likely that next to environmental fac- tors, host genetics may also impact the composition of our microbiome, and thereby play a crucial early role in defining disease susceptibility. In contrast, one might also reason that dysbiosis is primarily the result of exter- nal environmental factors, and that genetic factors only come to play a role when dysbiosis is already present. Another interesting question is whether disease results from small or rather broad alterations in microbial com- munities, and whether either the absence or the pres- ence of specific bacteria are key. Furthermore, next to the gut microbiome, there are now indications that also the microbiome from other body sites, such as the oral cavity and respiratory tract, may play a role, which was
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Epidemiology of juvenile idiopathic arthritis in Oman

Epidemiology of juvenile idiopathic arthritis in Oman

The medical records of the pediatric patients were retrospectively reviewed and information was collected including date of birth, age, gender, age at diagnosis, disease duration, joint involvement, JIA onset type and treatment. Immunological parameters collected included antinuclear antibodies (ANA), measured by indirect immunoflorescence and RF as detected by ELISA. Hu- man leukocyte antigen (HLA) was evaluated on conven- tional lymphocytotoxicity assay in a few of the patients who had onset of arthritis after the age of 6 years. ANAs was considered positive if a titer of ≥1:80 was obtained on at least 1 clinic visit during the disease course. RF was considered to be positive when titers were >20 IU/ml. If only one test of RF was performed, as was the case in many patients, then the results of this test were used to assign a JIA subtype rather than apply the subtype category of “other JIA.” All patients were screened for uveitis by an ophthalmologist using slit lamp examination during regular follow up visits at 3, 6 or 12 monthly intervals as per the pediatric screening recommendation for uveitis in JIA [4].
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Juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4 + T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling
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Vitamin D and juvenile idiopathic arthritis

Vitamin D and juvenile idiopathic arthritis

Considerations when evaluating the role of vitamin D in JIA include vitamin D requirements for this population and the role that vitamin D plays in disease activity. Using the specified MeSH search terms (vitamin D and childhood arthritis), 386 reports (full-text articles, conference abstracts, and letters to the editor) were identified. Thirty-eight studies met the inclusion criteria and are the subject of this review (Table 2). One meta-analysis reported cumulative 25(OH)D concentra- tions from fourteen studies comprising children with JIA, JCA, and JRA and other rheumatic conditions; this meta-analysis was not included in our scoping review but is referenced in the discussion [12]. This present review summarizes accumulated evidence on vitamin D and chronic childhood arthritis by disease activity and latitude. Additionally, this study provides new informa- tion about differences in 25(OH)D status between healthy controls and children with JIA.
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Ataxia Telangiectasia and Juvenile Idiopathic Arthritis

Ataxia Telangiectasia and Juvenile Idiopathic Arthritis

hexacetonide of the right ankle and left first metacarpophalangeal joint. His right ankle responded well to the therapy, but the improvement in the first metacarpophalangeal joint was modest ( Fig 4). After this treatment, disease activity in our patient as assessed by the Juvenile Arthritis Disease Activity Score-10, 5 which

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The autoimmune burden in juvenile idiopathic arthritis

The autoimmune burden in juvenile idiopathic arthritis

what disease. Moreover, the studies published till now refer to a pediatric population without a long-term follow-up. It is not clear how different ADs cluster to- gether but the present study showed how the incidence of AITD, the most frequent AD in general population, increases with time from the diagnosis of JIA, becoming very important after 12 years (cumulative incidence of 36%). Other ADs can develop early, even before arthritis. Although the environmental factors may influence fa- milial aggregation, the genetic load appears to be a rele- vant aspect. Familial autoimmunity is an important feature and should always be investigated during family history in patients with arthritis. Our study shows that familiarity for ADs is not negligible in JIA patients, since almost half of them had at least one relative affected by an AD. The presence of positive family history for ADs might be useful to guide the diagnostic pathway towards an autoimmune aetiology. Anyway, a positive familiarity for ADs does not correlate with a particular subtype of JIA and does not seem to lead to an earlier development of arthritis. Our study has some limitations like its retro- spective nature and the self-reporting of familial history. However, it is the first study that analyzes both polyau- toimmunity and familial aggregation of autoimmunity together in JIA patients.
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HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

netic processes, influencing the dynamic regulation of intracellular signaling path- ways. Detailed description of biochem- istry and mode of action of HDACs and their inhibitors have been reviewed (14). RA and JIA are systemic disorders in which autoimmune chronic inflamma- tion emerges from a variable combina- tion of individual genetic predispositions for dysregulated immune responses (15). This could explain possible positive in- fluences of epigenetic modifications on inflammatory gene responses. Numerous genes coding cytokines, chemokines and the expression of activating or inhibitory factors of immune cells are linked to per- sistence of chronic arthritis and result in functional changes in immunoregulatory and cell cycle networks (16). Recent knowledge about the importance of epi- genetic modulations in immunopatho- genesis of autoimmune diseases and the first encouraging results obtained in vitro and in vivo in animal models of arthritis, using epigenetic modulators have announced a possible new era in anti - rheumatic drug development (12,17,18).
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Profile of adalimumab and its potential in the treatment of uveitis

Profile of adalimumab and its potential in the treatment of uveitis

mediated causes of uveitis that can be treated with adali- mumab include juvenile idiopathic arthritis (JIA), sarcoidosis, Behçets disease, inflammatory bowel disease, and the spon- dyloarthropathies (often associated with human leukocyte antigen-B27), as well as noninfectious idiopathic uveitis. Less commonly, adalimumab has been used in the treatment of other rare diseases, such as Vogt–Koyanagi–Harada disease. The prevalence of associated systemic disease varies widely depending on age group, sex, and ethnicity. For example, in children, a majority (as high as 70%–80% in some references) of uveitis is idiopathic, with JIA being the most commonly associated systemic disease. 1 This paper will not specifically
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Efficacy and safety of adalimumab in ankylosing spondylitis

Efficacy and safety of adalimumab in ankylosing spondylitis

IL, USA), a fully human monoclonal antibody that binds to and neutralizes TNF, is approved for the treatment of AS, psoriatic arthritis, rheumatoid arthritis, psoriasis, juvenile idiopathic arthritis, and Crohn’s disease in many countries. Large, randomized, placebo-controlled clinical trials in patients with AS have shown impressive short-term improve- ments in spinal pain, function, and inflammatory markers with adalimumab, when self-administered subcutaneously every other week. Long-term studies have demonstrated the sustained efficacy of adalimumab, with a safety profile comparable with that of other anti-TNF agents.
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Impact of juvenile idiopathic arthritis on schooling

Impact of juvenile idiopathic arthritis on schooling

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 per- sistent 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 because of marked pain, malaise
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Outcome in juvenile idiopathic arthritis: a population based study from Sweden

Outcome in juvenile idiopathic arthritis: a population based study from Sweden

The long-term outcome of JIA has improved in the last three decades [11]. There are different criteria developed to study and define disease outcome. In 2004, Wallace et al. defined a set of criteria for evaluation of clinical out- come in JIA. Inactive disease was defined as a state of no joints with active arthritis, no uveitis, no systemic symp- toms, normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), and a physician’s global assess- ment of disease activity indicating no disease activity [12]. Using this definition, 47.5 ± 22.6% of the children achieved inactive disease after a median time of 6.5 ± 1.5 years, according to the data compiled in a review article on JIA outcome. Inactive disease and remission were achieved most often in the persistent oligoarticular subgroup, in contrast to the extended oligoarticular and RF+ sub- groups, where the prognosis for achieving remission was least favorable [13]. In the most recently published out- come study, 45.6% of the children had active disease at 18 years of follow-up [14]. However, validated outcome cri- teria are difficult to use in a retrospective study due to the need for patient-reported measures.
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Patient perceptions of foot disability in Juvenile Idiopathic Arthritis: a comparison of the juvenile arthritis foot disability index and the Oxford ankle foot questionnaire for children

Patient perceptions of foot disability in Juvenile Idiopathic Arthritis: a comparison of the juvenile arthritis foot disability index and the Oxford ankle foot questionnaire for children

The Children’s Chronic Arthritis Association (CCAA) is a UK registered charity providing a national support net- work for children with JIA and their families. Permission was granted by the CCAA to access children with JIA via their website for this questionnaire-based study. Use of the OxAFQ-C requires permission from ISIS Out- comes at the University of Oxford, and this was granted. Following ethical approval from the University of East London’s School of Health, Sport and Bioscience ethics committee, recruitment of children with JIA was under- taken through the CCAA website. The study was adver- tised on the CCAA website inviting children and parents to participate. A web-link was provided on the CCAA site which linked to the study website, allowing access to study information and consent forms. Following submis- sion of consent forms and receipt of information to en- sure the inclusion criteria (aged 5-16 years old, diagnosis of JIA made by a paediatric rheumatologist and includ- ing all subgroups of the disease) were met, the partici- pants were directed to the questionnaire pages on the website, powered by SurveyMonkey Inc.
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The joints in juvenile idiopathic arthritis

The joints in juvenile idiopathic arthritis

Synovial contrast enhancement, bone marrow oedema (BMO) and increased joint fluid are all thought to be signs of active inflammation. The presence of bone erosions is a sign of structural joint damage and the presence of BMO may be predictive of later bone erosions [27, 28]. These def- initions of active inflammation and destruction are based on research on patients with rheumatoid arthritis and have been adapted for use in children. Recent studies have shown that definitions extrapolated from research in the adult pop- ulation cannot automatically be used in children and may lead to both over- and under-staging of disease Fig. 9 MRI can be used to depict bone destruction. Coronal T1 TSE of
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Ultrasound in juvenile idiopathic arthritis

Ultrasound in juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and an import- ant cause of acquired disability in children [1]. Despite the heterogeneity, all forms of JIA are characterized by prolonged synovial inflammation that can cause cartil- age and bone damage, with severe impairment of phys- ical function and impact on the quality of life. In the recent years, the availability of powerful and expensive drugs increased the need to identify patients with a high likelihood of developing erosive damage early and patients with a less aggressive disease, so as to institute the appropriate therapy at and for the most convenient time. This induced to search for sensitive methods for reliable documentation and precise monitoring of the synovial inflammation process [2–4]. Musculoskeletal ultrasound (MSUS) demonstrated to be a valid and reliable tool in the assessment of chronic inflammatory arthropathies in adults [5–7]. Therefore, it has been
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Same but different? A thematic analysis on adalimumab biosimilar switching among patients with juvenile idiopathic arthritis

Same but different? A thematic analysis on adalimumab biosimilar switching among patients with juvenile idiopathic arthritis

Keywords: Paediatric rheumatology, Juvenile idiopathic arthritis, Uveitis, Biosimilars, Adalimumab, Qualitative.. Background.[r]

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The effect of immunomodulators on the immunogenicity of TNF blocking therapeutic monoclonal antibodies: a review

The effect of immunomodulators on the immunogenicity of TNF blocking therapeutic monoclonal antibodies: a review

We performed a systematic PubMed search of articles on the subject of concomitant immunosuppressive therapy with TmAb treatment. Search terms were infl iximab, adalimumab, rheumatoid arthritis, ankylosing spondy- litis, psoriatic arthritis, psoriasis, Crohn disease, juvenile idiopathic arthritis, juvenile rheumatoid arthritis, immuno- genicity, antibodies, anti-adalimumab antibodies, anti- infl iximab antibodies, methotrexate, MTX, and immuno- modulators. Articles were selected if a full text was available and if the formation of antibodies against adalimumab/infl iximab and the possible eff ect of immunomodulators on immunogenicity were described. CLMK and GMB performed the PubMed search and evaluated all of the articles.
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