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 PostPoslano: 20-01-2009 14:29  Citiraj (i odgovori)  
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Adalimumab in the therapy of uveitis in childhood

http://bjo.bmj.com/cgi/content/abstract/91/3/319

Purpose: Chronic anterior uveitis in children often takes a serious course. Despite various immunosuppressive drugs some children do not respond sufficiently and there is a high risk of them becoming seriously disabled. Anti-TNF alpha therapy has been shown by our group and others to be mostly ineffective (Etanercept) or partly effective (Infliximab) with the risk of anaphylactic reactions. Here we report on 18 young patients treated with Adalimumab (Humira®), a complete humanised anti-TNF alpha antibody.
Methods: We retrospectively analysed 18 patients, who were treated with Adalimumab (20–40 mg, every 2 weeks, when ineffective every week); 17 had juvenile idiopathic arthritis, one was without detectable underlying disease. The age at onset of arthritis varied from 0.5–15 years and for uveitis from 2–19 years. Patients were included when the previous anti-inflammatory therapy had been ineffective. It consisted of systemic steroids (n = 18, Cyclosporin A (n = 18, Methotrexate (n = 18, Azathioprine (n = 12, Mycophenolate mofetil (n = 4), Cyclophosphamide (n = 2), Leflunomide (n = 3), Etanercept (n = 8 and Infliximab (n = 5). The grading for uveitis was: (a) effective: no relapse or more than two relapses less than before treatment, (b) mild: one relapse less than before treatment, (c) no response: no change in relapse rate and (d) worsening: more relapses under treatment than before. The grading for arthritis (depending on the clinical findings), using three out of six parameters of the ACR PED Criteria, was: effective, mild, no response, worsening.
Results: For arthritis (n = 16) the response to Adalimumab was effective in 10 of 16 patients, mild in three patients, three did not respond. For uveitis (n = 18 Adalimumab was effective in 16, mild in one child, and one patient did not show any effect. After a very good response initially a shorter application time had to be used to maintain the good anti-inflammatory effect in one child. Additional immunosuppressive treatment was used in seven of the effectively treated children. Due to elevation of liver enzymes in one patient, who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions or increased frequency of infections since start of Adalimumab treatment was reported.
Conclusions: For our group of children with long lasting disease our results show that Adalimumab was effective or mildly effective against the arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems to be much more effective against uveitis than Etanercept. Anaphylactic reactions, found in a previous study from our group after Infliximab treatment, were not seen with Adalimumab. The necessary dosage and the treatment period, which probably have to be defined individually for each patient, remain unclear.

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Anita Moorjani "Ponovno rodjena"


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 PostPoslano: 03-02-2009 16:13  Citiraj (i odgovori)  
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Rheumatoid Arthritis: Study Provides First Evidence Of Clinical Response To Gene Therapy


A study that delivers the first clinical evidence that gene therapy can reduce the symptoms of patients with rheumatoid arthritis appeared in the February issue of Human Gene Therapy. The authors of the study, which was carried out in 1997 and 1998 under the direction of Dr. Peter Wehling, Düsseldorf, Germany, describe the findings of a study involving two patients with severe rheumatoid arthritis.

In gene therapy, genes inside the cells are modified so as to either repair a genetic defect or to trigger the cells to produce a protein that stops the disease. The first clinical studies of such techniques began in 1990 for the treatment of rare genetic defects of the immune system. The gene transfer technique used in the present study was approved by the Ethics Committee of the Düsseldorf University Hospital.

Rheumatoid arthritis is a classic auto-immune disorder in which the body's immune system turns against itself, resulting in swelling and inflammation of the joints. The disease causes permanent destruction of joint tissue, especially cartilage, and remains incurable. It is estimated that 5-10 million patients of the EU suffer from rheumatoid arthritis. "Rheumatoid arthritis is an extremely painful condition that can affect multiple joints of the body. It is an ideal indication for this technique because the joint forms a closed space. The genetically modified cells can simply be injected into the joint because they will stay in place", notes Dr. Rüdiger Krauspe, director of the Orthopaedics Clinic at Düsseldorf University Hospital.

Lead investigator Peter Wehling explains the technique: "We injected genetically modified cells taken from the patient's own body into the diseased joint. This stimulated the production of the human interleukin-1 receptor antagonist, which stops the breakdown of cartilage by blocking the interleukin-1 protein that is responsible for the inflammatory processes." "Essentially the gene becomes its own little factory, continuously working to alleviate pain in the joint ", says Christopher H. Evans of the Center for Molecular Orthopaedics, Harvard Medical School, Boston, one of the co authors of the study.

"Basically we were able to show that gene therapy is feasible and safe for arthritic disorders", said co-author Dr. Julio Reinecke, molecular biologist with Orthogen, a Düsseldorf biotechnology company.

The study involved two female patients, both under the age of 75, with a diagnosis of advanced rheumatoid arthritis. (Due to complications related to an unrelated trial for a different immunodficiency disorder, only two of the six subjects originally approved to take part in the trial could be included.) Four weeks after receiving the injections, both patients reported reduced pain and swelling. In one of the subjects the effects were dramatic. The treated joint remained free of pain even when the patient experienced further flares of her symptoms in other, untreated joints. Laboratory testing of tissue from the treated joint showed lesser quantities of the interleukin-1 proteins, thus confirming that the reduced pain and swelling were results of the gene therapy.

The study shows that gene therapy produces clinical results and symptomatic relief in the treatment of rheumatoid arthritis, and that the method can be considered safe, at least over the period observed thus far. Further studies are needed to confirm this promising approach. The study was funded in part by grants from the Land of North-Rhine Westphalia and Orthogen AG.

The study was conducted jointly by the Düsseldorf University Hospital Orthopaedics Clinics, Orthogen Düsseldorf, and the University of Pittsburgh School of Medicine, along with Steven Ghivizzani of the University of Florida College of Medicine und Christopher H. Evans of the Center for Molecular Orthopaedics, Harvard Medical School, Boston.

http://www.wehling-hartmann.de
http://www.medicalnewstoday.com/articles/137583.php

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Anita Moorjani "Ponovno rodjena"


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 PostPoslano: 08-02-2009 12:57  Citiraj (i odgovori)  
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Neutrophils: the forgotten cell in JIA disease pathogenesis
http://www.pubmedcentral.nih.gov/articl ... id=1904449

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 PostPoslano: 17-04-2009 12:44  Citiraj (i odgovori)  
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OU researchers announce juvenile arthritis find
4/16/2009, 6:53 p.m. EDT

http://www.mlive.com/newsflash/health/i ... ist=health

Otkriće Biomarkera kojim se potvrđuje remisija i koji će pomoći odluci dr o prestanku uzimanju lijekova

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Dr. Punaro , Scottish Rite hospital na konferenciji u Houstonu rekao da sada postoji kožni test koji može pomoći odrediti koji će lijekovi biti najučunkovitiji za djecu s JIA

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Objavljeno 30.06.2009 u 14:26:56
Lijek Humira - pomoć oboljelim tinejdžerima


Napokon lijek za juvenilni idiopatski artritis u djece
Lijek Humira, farmaceutske tvrtke Abbott, od sada je u Hrvatskoj registriran i za liječenje juvenilnog idiopatskog artritisa (JIA) u adolescenata od 13 do 17 godina, a odobren je za pacijente kod kojih u prethodnom liječenju antireumaticima nije postignut zadovoljavajući odgovor, objavila je danas tvrtka Abbott.
Lijek Humira u Hrvatskoj je već od ranije registriran za liječenje reumatoidnog artritisa, psorijatičnog artritisa, ankilozantnog spondilitisa, Chronove bolesti, te se nalazi na listi lijekova HZZO-a i primjenuje kod odraslih bolesnika.

Juvenilni idiopatski artritis utječe na pet ili više zglobova te je najčešći oblik artritisa u djece, a u Abbotu procjenjuju da je u ovom trenutku potreban za pedesetak djece u Hrvatskoj.

Humira je prvi novi biološki lijek za oboljele od JIA predstavljen u posljednjih osam godina. Ujedno je prvi koji omogućava gotovo samostalno liječenje kod kuće dozama koje se primjenjuju svaki drugi tjedan.

U Hrvatskoj je odobren pošto je u rujnu prošle godine registriran u Europi.

Bolest JIA se uglavnom javlja prije 16. godine, a simptomi uključuju trajno oticanje zglobova, bol i ukočenost. Bolest može zahvatiti bilo koji zglob, a upala ograničiti njegovu pokretljivost. Cilj liječenja je kontrola upale, ublažavanje boli, očuvanje pokretljivosti i funkcije zglobova, kao i sprječavanje napredovanja bolesti.

Lijek je odobren na temelju kliničke studije koja je trajala 48 tjedana i obuhvatila 171 dijete, a rezultati su pokazali brzo, značajno i kontinuirano poboljšanje znakova i simptoma bolesti.
(Hina)

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 PostPoslano: 15-07-2009 17:35  Citiraj (i odgovori)  
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Subclinical Markers Predict Relapse In Juvenile Idiopathic Arthritis Post Methotrexate Withdrawal
Main Category: Arthritis / Rheumatology
Also Included In: Pediatrics / Children's Health
Article Date: 13 Jun 2009 - 0:00 PDT

Elevated levels of the inflammatory biomarkers Myeloid Related Protein (MRP*) 8/14 predict an increased risk of relapse following withdrawal of methotrexate (MTX) therapy in children with juvenile idiopathic arthritis (JIA) who have achieved inactive disease status, according to a new study presented at PReS 2009, a joint congress with the 2009 Congress of the European League Against Rheumatism (EULAR) in Copenhagen, Denmark.

Effective treatment options are available to treat rheumatic diseases, many of which have the potential to induce remission, defined as absence of signs or symptoms of disease. While there is evidence-based advice regarding when to initiate therapy in rheumatic diseases, there is no specific guidance on the timing of treatment withdrawal once a state of remission on medication is achieved. While this holds true for many autoimmune disease (such as Rheumatoid Arthritis, Crohn's disease, Ulcerative Colitis, or Autoimmune Hepatitis), in the case of MTX therapy for JIA, a continuation of MTX for 12 to 24 months after induction of remission has been proposed by researchers.1

The risk of relapse in JIA patients, once MTX is discontinued, is approximately 50%.2 However, the results of this study have shown that continuing MTX therapy past the point of remission does not affect the risk of relapses after withdrawal of therapy. Clinical (disease subtype, duration or dosage of therapy, duration of MTX therapy) or standard laboratory tests (c-reactive protein and erythrocyte sedimentation rate as measurements of inflammation) could not differentiate between patients at-risk for relapse and those without this risk. However, MRP8/14 levels were significantly higher at MTX withdrawal in remission in those patients who subsequently developed relapses (715±140 ng/ml) compared to patients with stable remission (400±105 ng/ml; p=0.003).

Levels of MRP8/14 were especially high in patients with relapses occurring within 6 months, compared to 12 months. (955±270 ng/ml; p< 0.001).

Professor Dirk Foell of the University of Muenster, Germany, who conducted the study, said: "Methotrexate is effective in children with JIA and can induce a status of inactive disease. This is the first controlled trial analyzing the necessary time of treatment continuation once remission is achieved in a rheumatic disease. Our study shows that patients with elevated levels of MRP 8/14 may specifically benefit from prolonged treatment and also that a longer duration of MTX therapy after achieving remission does not influence the risk of relapse on patients with JIA. The results of our research help to make the case for the tracking of levels of biomarkers as predictors of treatment responses in this unique patient population."

In the PRINTO** study, 364 JIA patients with inactive disease for at least 3 months were randomised to receive additional MTX for either 6 or 12 months. Serum sample analysis using ELISA (Enzyme-Linked Immunosorbent ***) was conducted in 188 patients to track MRP8/14 levels at 3 month baseline, and again at either 6 or 12 months according to study protocol. Patients were followed-up for at least 12 months after MTX discontinuation.

A log-rank analysis confirmed the differences in relapse rates between patients with MRP8/14 levels of 900ng/ml or above, compared to those with lower levels (p< 0.001). ROC (Receiver operating characteristics) analysis revealed a sensitivity of 50% and a specificity of 78% for predicting relapses at this cut-off (likelihood ratio for relapse 2.3), while the specificity was increased to 90% at a cut-off at 1400ng/ml (likelihood ratio 3.4).

At baseline, demographic and clinical characteristics were well balanced and all patients had inactive disease status. 59 (31%) had the JIA subtype of persistent oligoarthritis, 27 (14%) extended oligoarthritis, 64 (34%) polyarthritis RF-negative, 10 (5%) polyarthritis RF-positive, 12 (6%) systemic and 16 (9%) other JIA subtypes. Patients had previously been treated with MTX at a dose of 11.6±2.8 mg/m2/week for 2.3±2.1 years. The overall rate of flares was 92/188 (49%) patients.

JIA is the most common inflammatory autoimmune childhood disease, affecting approximately 1 in 1,000 children. Despite advances in diagnosis and treatment options, it remains a chronic condition for most affected children with a significant disease burden.

Notes:
*MRP 8 and 14 are pro-inflammatory damage *** molecular pattern (DAMP) molecules that play an important role in inflammatory and immunological responses. They have recently been identified as activators of Toll like receptor (TLR-4), a molecule that amplifies phagocyte activation (a type of white blood cell (leukocyte), that supports the immune system by neutralising or engulfing bacteria or other invading micro-organisms.
**PRINTO (Paediatric Rheumatology International Trials Organization) is an international not-for-profit research network that fosters, facilitates and co-ordinates international trials of children with rheumatic diseases

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Better Classification And Treatment Of Juvenile Arthritis Via Gene Expression

Scientists have discovered gene expression differences that could lead to better ways to classify, predict outcome, and treat juvenile idiopathic arthritis (JIA). Eventually such findings could enable doctors to target more aggressive treatment to children at risk of more severe arthritis, while those likely to have milder disease could be spared the stronger treatments that carry a greater risk of side effects. The researchers were supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health.

JIA is an inflammatory and sometimes disabling joint disease that affects an estimated 294,000 children in the United States. At present, making a diagnosis of JIA is imprecise and based largely on the presence of joint inflammation persisting for at least six weeks, for which no other cause can be determined, says Robert A. Colbert, M.D., Ph.D., chief of the NIAMS Pediatric Translational Research Branch. Based on the number of joints involved and other clinical features (fever and rash, for example), doctors classify patients into one of four or five major subtypes of JIA, which helps them predict a patient's most likely outcome and guide appropriate treatments. "But, recent research suggests there is more variability in JIA than the four or five major subtypes we currently recognize," Dr. Colbert says.

In the first of two such NIAMS-supported studies to be published in the July issue of Arthritis & Rheumatism, scientists led by Michael Barnes, Ph.D., of Cincinnati Children's Hospital Medical Center used a large data set to compare a number of children newly diagnosed with one of four major subtypes of JIA - persistent oligoarthritis (affecting four or fewer joints), polyarthritis (affecting five or more joints), systemic arthritis (with fever and rash and inflammation throughout the body) and enthesitis-related arthritis (affecting the junctions between tendons and bones). Using gene expression technology - a method by which scientists can determine the relative levels of expression of thousands of different genes at the same time and compare a pattern from one subject with another - the researchers looked for differences in the children's blood samples that corresponded with the different forms of JIA.

"We analyzed gene expression patterns in blood cells and found that we could indeed distinguish the major subtypes of JIA," says Dr. Colbert, who was a leader of this research program at Cincinnati Children's Hospital Medical Center before coming to NIAMS. "Many of the genes whose expression is altered function in the immune system. This means that not only is there immune activation, but it differs depending on the subtype of JIA that is present."

In the second study, led by Thomas Griffin, M.D., Ph.D., also at Cincinnati Children's Hospital Medical Center, scientists looked more closely at patients from the study with one particular subtype of the disease - polyarticular JIA - to determine if that form was more complicated, or if there were more subgroups than originally thought. They included children with rheumatoid factor (RF) positive JIA, meaning their blood tested positive for an antibody commonly seen in adults with rheumatoid arthritis (RA). Surprisingly, the scientists found patterns of gene expression that indicated at least three subgroups of polyarthritis. There was an older subgroup (average age 11) that included both RF positive and negative children with an inflammatory gene expression signature bearing some resemblance to adult RA. A second older subgroup (RF negative) had less severe arthritis and an anti-inflammatory gene expression signature. A third subgroup was comprised mostly of younger patients (average age 7) who had no clearly defined gene expression signature and did have antinuclear antibodies (ANA). This third subgroup may be more similar to oligoarthritis patients, who frequently have a positive ANA, than to the other subgroups of polyarticular JIA.

Dr. Colbert says the new findings take pediatric rheumatologists a step closer to more precisely classifying JIA, and eventually developing individually tailored treatments that maximize the benefits, while minimizing the risks. "In pediatric rheumatology, we are at the early stages of improving our classification system for JIA. We expect that complementary studies designed to uncover the genetic differences that contribute to susceptibility will confirm the presence of several JIA subtypes, and add important information about what causes this group of diseases," he said. "We look forward to the day when we can use a combination of genetic and gene expression tests in the clinic to help us better diagnose and treat childhood arthritis."

In addition to NIAMS, funding for the studies was provided by the Cincinnati Children's Hospital Research Foundation and the Arthritis Foundation Ohio Valley Chapter.

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Anita Moorjani "Ponovno rodjena"


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EULAR 2009: Etanercept Safe, Effective in Young Children With Juvenile Idiopathic Arthritis
Alice Goodman

*** clinically focused product information on Medscape.
Click Here for Product Infosites – Information from Industry. June 16, 2009 (Copenhagen, Denmark) — Etanercept appears to be safe and effective in children younger than 4 years with juvenile idiopathic arthritis (JIA), a group for whom data are lacking with this treatment, according to results from an open-label pilot study. Children in the study were followed at a large tertiary-care hospital and appeared to have more severe JIA than those seen in general clinical practice.

"In patients under the age of 4 years, etanercept had similar efficacy in reducing disease and maintaining disease remission [as older children], with a similar safety profile. However, we need larger randomized studies to confirm this observation," said Antonella Insalaco, MD, from Ospedale Pediatrico Bambino Gesù in Rome, Italy, who presented the findings here at EULAR 2009: The Annual European Congress of Rheumatology.

"It's absolutely necessary to characterize the role of etanercept in a double-blind controlled study, which we are planning to do in the future," said lead author Claudia Bracaglia, MD, a pediatric rheumatologist at Ospedale Pediatrico Bambino Gesù.

Etanercept is not approved in Europe for the treatment of JIA patients younger than 4 years, she explained. This drug has shown safety and efficacy in clinical trials of older children with JIA, with no increase in serious adverse events after as long as 8 years of follow-up, Dr. Insalaco explained.

The study involved 33 patients younger than 4 years (24 girls and 9 boys) who had JIA and who did not respond to methotrexate. Mean disease duration was 12 months. Patients were treated with etanercept (dose range, 0.8 to 1.0 mg/kg) for a mean of 23 months (range, 6 to 86 months). Eight patients (24%) presented with systemic onset of JIA, 18 (58%) presented with oligoarticular onset (5 persistent, 13 extended), 6 presented with polyarticular onset (rheumatoid-factor negative), and 1 (3%) presented with psoriatic arthritis.

All patients were taking concomitant drugs: 31 were taking methotrexate and 2 were taking cyclosporine. After 6 months of treatment, 82% of patients achieved at least a 30% improvement on the American College of Rheumatology scoring system (ACR30), 63% achieved at least a 50% improvement (ACR50), and 42% achieved at least a 70% improvement (ACR70). At the last follow-up, response rates on these measures were 85%, 85%, and 73%, respectively. Five patients (5%) stopped taking etanercept because of a lack of efficacy after 5 months; 1 was switched to a different tumor necrosis factor (TNF)-alpha inhibitor and 4 were switched to an interleukin-1 blocker.

No major adverse events were reported in 82% of the study population. Four patients (12%) had a major adverse treatment-related event: 3 varicella zoster virus infections (1 requiring hospitalization for necrotizing fasciitis) and 1 cytomegalovirus infection. Dr. Insalaco said that now all patients are routinely vaccinated for varicella zoster virus prior to treatment with methotrexate or TNF-alpha agents. No patient treated with etanercept developed tuberculosis, other viral infection, or malignancy.

These data in younger children compare favorably with historic data in children 5 to 20 years with JIA treated with etanercept, she said.

Aggressive Treatment Questioned

The session moderators — Silvia Magni-Manzoni, MD, from Fondazione San Matteo in Pavia, Italy, and Freddy Karup homoseksualac, MD, from University Hospital Rigshospitalet in Copenhagen, Denmark — agreed that this represented a larger cohort of JIA children with more severe disease than would be expected at a regular clinic.

Both physicians said that it was surprising how aggressively the younger children in this study were treated. "In many places, [nonsteroidal anti-inflammatory drugs] are used, especially for children with oligoarthritis. It is not routine to use methotrexate and TNF-alpha inhibitors in such young children,"

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Variants in TNFAIP3, STAT4, and C12orf30 loci *** with multiple autoimmune diseases are also *** with juvenile idiopathic arthritis.Prahalad S, Hansen S, Whiting A, Guthery SL, Clifford B, McNally B, Zeft AS, Bohnsack JF, Jorde LB.
Emory University School of Medicine, Atlanta, Georgia.

OBJECTIVE: Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants *** with rheumatoid arthritis (RA) and other autoimmune disorders for *** with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors. METHODS: Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan ***, subjects were genotyped for 8 single-nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the TNFAIP3 locus, rs6679677 in the RSBN1 locus, rs17696736 in the C12orf30 locus, rs3761847 in the TRAF1/C5 locus, rs2104286 in the IL2RA locus, rs7574865 in the STAT4 locus, and rs2542151 in the PTPN2 locus. Alleles and genotypes were analyzed for *** with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The strongest *** with JIA risk or protection were observed for TNFAIP3 variants rs10499194 (OR 0.74 [95% CI 0.61-0.91], P < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05-1.61], P = 0.015). We also observed *** between JIA and both STAT4 (OR 1.24 [95% CI 1.02-1.51], P = 0.029) and C12orf30 (OR 1.20 [95% CI 1.01-1.43], P = 0.041) variants. The PTPN2 variant rs2542151 deviated from Hardy-Weinberg equilibrium and was excluded from analyses. Variants in IL2RA, TRAF1/C5, and RSBN1 were not *** with JIA. After stratification by JIA subtype, the TNFAIP3 and C12orf30 variants were *** with oligoarticular JIA, while the STAT4 variant was *** primarily with polyarticular JIA. CONCLUSION: We have demonstrated *** between JIA and variants in the TNFAIP3, STAT4, and C12orf30 regions that have previously shown *** with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors

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Connection of the IL2RA/CD25 gene with juvenile idiopathic arthritis.
Hinks A, Ke X, Barton A, Eyre S, Bowes J, Worthington J, Thompson SD, Langefeld CD, Glass DN, Thomson W; UK Rheumatoid Arthritis Genetics Consortium; British Society of Paediatric and Adolescent Rheumatology Study Group.
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Wilson AG, Morgan A, Emery P, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Symmons D, Abinum M, Becker M, Bell A, Craft A, Crawley E, David J, Foster H, Gardener-Medwin J, Griffin J, Hall A, Hall M, Herrick A, Hollingworth P, Holt L, Jones S, Pountain G, Ryder C, Southwood T, Stewart I, Venning H, Wedderburn L, Woo P, Wyatt S.

University of Manchester, Manchester, UK. Anne.Hinks@manchester.ac.uk

OBJECTIVE: IL2RA/CD25, the gene for interleukin-2 receptor alpha, is emerging as a general susceptibility gene for autoimmune diseases because of its role in the development and function of regulatory T cells and the *** of single-nucleotide polymorphisms (SNPs) within this gene with type 1 diabetes mellitus (DM), Graves' disease, rheumatoid arthritis (RA), and multiple sclerosis (MS). The aim of this study was to determine whether SNPs within the IL2RA/CD25 gene are *** with juvenile idiopathic arthritis (JIA). METHODS: Three SNPs within the IL2RA/CD25 gene, that previously showed evidence of an *** with either RA, MS, or type 1 DM, were selected for genotyping in UK JIA cases (n=654) and controls (n=3,849). Data for 1 SNP (rs2104286) were also available from North American JIA cases (n=747) and controls (n=1,161). *** analyses were performed using Plink software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: SNP rs2104286 within the IL2RA/CD25 gene was significantly *** with UK JIA cases (OR for the allele 0.76 [95% CI 0.66-0.88], P for trend=0.0002). A second SNP (rs41295061) also showed modest evidence for *** with JIA (OR 0.80 [95% CI 0.63-1.0], P=0.05). *** with rs2104286 was convincingly replicated in the North American JIA cohort (OR 0.84 [95% CI 0.65-0.99], P for trend=0.05). Meta-analysis of the 2 cohorts yielded highly significant evidence of *** with JIA (OR 0.76 [95% CI 0.62-0.88], P=4.9x10(-5)). CONCLUSION: These results provide strong evidence that the IL2RA/CD25 gene represents a JIA susceptibility locus. Further investigation of the gene using both genetic and functional approaches is now required.

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Biomarkers of Chronic Uveitis in Juvenile Idiopathic Arthritis:
Predictive Value of Antihistone Antibodies and Antinuclear Antibodies.Nordal EB, Songstad NT, Berntson L, Moen T, Straume B, Rygg M.
From the Department of Pediatrics, University Hospital of North Norway;

OBJECTIVE: To study the predictive value of antinuclear autoantibody (ANA) tests and antihistone antibodies (AHA) as risk factors for development of chronic asymptomatic uveitis of insidious onset in juvenile idiopathic arthritis (JIA).

METHODS: ANA by indirect immunofluorescence using HEp-2 cells (IF-ANA), ELISA for ANA (E-ANA), and AHA were analyzed in sera of 100 children with recent-onset JIA and in 58 control sera. Clinical features, including age at onset, JIA subgroup, and presence of uveitis, were recorded in this prospective population-based cohort study. RESULTS: E-ANA was positive in 4 of the 100 sera, and was not *** with uveitis. Chronic uveitis developed in 16 children with JIA: in 14 of 68 positive for IF-ANA>/= 80, and in 13 of 44 positive for AHA >/= 8 U/ml. IgM/IgG AHA were found in higher proportions in children with uveitis (mean 12.4 U/ml) than in those with JIAand no uveitis (mean 6.9 U/ml) or in healthy controls (mean 4.3 U/ml).

CONCLUSION: No conn. was found between E-ANA and uveitis, and most IF-ANA-positive sera were E-ANA-negative. E-ANA is not clinically relevant in this setting and should never be used to determine frequencies of eye examinations to detect new uveitis in JIA.AHA>/= 8 U/ml, IF-ANAtiter >/= 320, and young age at onset of arthritis were significant predictors for development of chronic uveitis. The diagnostic value of AHA >/= 8 U/ml as a biomarker of chronic uveitis in JIA is very similar to IF-ANA >/= 80.

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Anita Moorjani "Ponovno rodjena"


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Ocular threat in juvenile idiopathic arthritis.

Marvillet I, Terrada C, Quartier P, Quoc EB, Bodaghi B, Prieur AM.
Centre national de référence Arthrite Juvénile, Unité d'Immunologie-Hématologie et Rhumatologie Pédiatriques, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75 015 Paris, France.

OBJECTIVES: Uveitis is the most severe complication of juvenile idiopathic arthritis (JIA). The diagnosis may be delayed, as visual symptoms are usually absent, which provides time for insidious complications. The course is chronic and long-term treatment is therefore required. METHODS: We retrospectively reviewed the medical records of 75 children with uveitis who accounted for 10.5% of all patients with JIA seen at our pediatric rheumatology outpatient clinic between July 1997 and July 2007.

RESULTS: Uveitis occurred chiefly in patients with pauciarticular JIA. At last follow-up, in 69 patients in whom the files could be satisfactorily reviewed, only the anterior compartment was involved in 59.4% and both the anterior and the posterior compartments in the remainder. Mean age at the uveitis diagnosis was 4.5 years. In 9 (13.0%) patients, uveitis antedated joint manifestations; in 17 (24.7%) both were diagnosed simultaneously; and in 43 (62.3%) arthritis antedated uveitis. In 42 (61%) patients, complications occurred (synechiae, papillary block, cataract, hyalitis, papilledema, glaucoma, macular edema, elevated intraocular pressure, vision loss, and hypotonia). Topical medications were used in all patients for at least 3 months. Severe ocular involvement required systemic glucocorticoid therapy in 29 (42.0%) patients. Among immunomodulating agents, methotrexate and cyclosporine were used in 41 patients and TNFalpha antagonists in 15 patients. Surgery was performed in 21 (30.4%) patients. Uveitis completely resolved in 12 (17.4%) patients, a relapsing course occurred in 14 (20.3%), and became chronic with relapses as soon as the topical treatment was decreased in 23 (33.3%). A severe course was observed in 21 (30.4%) patients of whom 3 became blind and 4 lost vision in one eye.

CONCLUSION: Uveitis is a severe complication of JIA. Patients with JIA should receive routine ophthalmological follow-up at regular intervals, even is their joint disease is quiescent.

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Anita Moorjani "Ponovno rodjena"


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 PostPoslano: 16-07-2009 13:19  Citiraj (i odgovori)  
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Searching for intraocular antibody production against Parvovirus B19, Mumps virus and Measles virus in patients with intermediate and posterior uveitis

N Visser1,2, A Rothova2, J D F de Groot-Mijnes1 and L de Visser1,2
Accepted 30 December 2008

The first 150 words of the full text of this article appear below.

Uveitis is a destructive ocular inflammation and is caused by either infectious agents or non-infectious immune reactions. The aetiology is still unknown in about 50% of the patients. The distinction between an infectious and non-infectious aetiology is crucial for treatment and prognosis. The main infectious agents in the West include Toxoplasma gondii, Herpes simplex virus (HSV), Varicella zoster virus (VZV), Cytomegalovirus (CMV) and Rubella virus, pathogens which are also the most frequent causes of congenital and childhood infections. Several case reports have mentioned uveitis following Parvovirus, Mumps or Measles infection.1–3 Despite the MMR-vaccination programme, Mumps and Measles outbreaks continue to occur.4 We hypothesised that other common viral childhood infections might also be able to incite uveitis and selected Parvovirus B19, Mumps virus and Measles virus as the most likely candidates. We included specific classified uveitis entities occurring at a relatively young age: intermediate uveitis, neuroretinitis and focal chorioretinitis of . .

http://bjo.bmj.com/cgi/content/extract/93/6/841

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