Form Of Juvenile Rheumatoid Arthritis Research Articles

Тоцилізумаб у лікуванні ювенільного ревматоїдного артриту

У розвитку ревматичних хвороб, особливо при ювенільному ревматоїдному артриті, доведена важлива роль окремих цитокінів, найважливішими серед яких є інтерлейкін-1, інтерлейкін-6 та фактор некрозу пухлини α. Новим словом у лікуванні даної групи хвороб є імунобіологічні препарати. Препарат гуманізованих антитіл проти рецепторів інтерлейкіну-6 тоцилізумаб є високоефективним та безпечним засобом для лікування системної та поліартикулярної форми ювенільного ревматоїдного артриту. 1. Александрова Е.Н., Панасюк Е.Ю., Авдеева А.С. и др. Динамика лабораторных маркеров у больных ревматоидным артритом на фоне терапии тоцилизумабом // Научно-практическая ревматология. — 2011. — № 3. — С. 14-19.2. Бережний В.В., Марушко Т.В., Роменкевич І.В. Стан надання кардіоревматологічної допомоги дітям України за 2009 р. // Современная педиатрия. — 2010. — № 5(33). — С. 14-18.3. Уніфікований клінічний протокол медичної допомоги дітям, хворим на ювенільний артрит. Затверджений Наказом МОЗ України № 832 від 22.10.12.4. Brunner H., Ruperto N., Zuber Z. et al. Efficacy and safety of tocilizumab in patients with polyarticular juvenile idiopathic arthritis: data from a phase 3 trial [abstract no. 1597] // Arthritis Rheum. — 2012. — Vol. 64. — P. S682.5. Cassidy J.T., Petty R.E. Textbook of Pediatric Rheumatology. 5th ed. — Philadelphia: W.B. Saunders Company, 2005. — 792 p. 6. De Benedetti F., Brunner H.I., Ruperto N. et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis // N. Engl. J. Med. — 2012. — Vol. 367(25). — P. 2385-2395. 7. Frampton F.E. Tocilizumab: A Review of Its Use in the Treatment of Juvenile Idiopathic Arthritis // Pediatric Drugs. — Vol. 15, Issue 6. — P. 515-531.8. Genentech Inc. Actemra® (tocilizumab) injection, for intravenous infusion. US prescribing information. 2013. http://www.gene.com/ download/pdf/actemra_prescribing.pdf. Accessed 2 Sep 2013.9. Henter J.I., Horne A., Aricó M., Egeler R.M., Filipovich A.H. et al. Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis // Pediatric Blood Cancer. — 2007. — Vol. 48. — P. 124-131.10. Hoffman-La Roche. A study of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis [ClinicalTrials.gov identifier NCT00988221]. US National Institutes of Health, ClinicalTrials.gov [online]. 2012. http://clinicaltrials.gov/ct2/show/record/NCT00988221. Accessed 2 Sep 2013.11. Hoffman-La Roche. Roche trials database. Clinical trial result information. Protocol number: WA19977. 2012. http://www.roche-trials.com/studyResultGet.action?studyResultNumber=WA19977. Accessed 2 Sep 2013. 21.12. Immonen K., Savolainen A., Kautiainen H., Hakala M. Longterm outcome of amyloidosis associated with juvenile idiopathic arthritis // Journal of Rheumatology. — 2008. — Vol. 35, № 5. — P. 907-912. 13. Packard R., Libby P. Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction // Cli­nical Chemistry. — 2008. — Vol. 54. — P. 24-38. 14. Petty R.E., Southwood T.R., Manners P. et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001 // Journal of Rheumatology. — 2004. — Vol. 31. — P. 390-392. 15. Ravelli A., Martini A. Juvenile idiopathic arthritis // Lancet. — 2007. — Vol. 369. — P. 767-778. 16. Roche Pharma AG. RoActemra 20 mg/mL concentrate for solution for infusion. EU summary of product characteristics 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_Product_Information/human/000955/WC500054890.pdf. Accessed 2 Sep 2013.17. Stéphan J.L., Koné-Paut I., Galambrun C., Mouy R., Ba­der-Meunier B., Prieur A.M. Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients // Rheumatology. — 2001. — Vol. 40, № 11. — P. 1285-1292. 18. Tanaka T., Ogata A., Narazaki M. Tocilizumab for treatment of rheumatoid arthritis // Expert rewiew in clinical immunology. — 2010. — Vol. 6. — P. 843-854. 19. Yokota S., Imagawa T., Mori M. et al. Efficacy and safety of tocilizumab in patients with systemic onset of juvenile idiopathic arthritis: a randomized, double blind, placebo-controlled, withdrawal phase III trial // Lancet. — 2008. — Vol. 371. — P. 998-1006.20. Yoshimura T., Sonoda K., Ohguro N. Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis // Rheumatology. — 2009. — Vol. 48 (4). — P. 347-354. 21. Zhang X., Morcos P.N., Saito T. et al. Clinical pharmacology of tocilizumab for the treatment of systemic juvenile idiopathic arthritis // Expert. Rev. Clin. Pharmacol. — 2013. — Vol. 6(2). — P. 123-137.

Гломерулярные поражения почек у детей с ювенильным ревматоидным артритом (обзор литературы)

Обзор литературы посвящен описанию различных форм гломерулонефрита (ГН) у детей с полиартикулярной и системной формами ювенильного ревматоидного артрита (ЮРА). В доступной литературе представлен 21 клинический случай развития ГН, а именно: ANCA-ассоциированный ГН, мезангиопролиферативный ГН, в том числе IgA- и IgМ-нефропатия, мембранозная нефропатия, фокально-сегментарный гломерулосклероз, болезнь минимальных изменений, экстракапиллярный ГН. Механизм гломерулярных поражений при ЮРА объясняется гиперпродукцией провоспалительных цитокинов, а также нефротоксическим действием базисных противовоспалительных лекарственных средств. Подробно проанализированы клинические проявления и эффективность проводимой терапии каждого варианта ГН у детей с ЮРА. Больше всего публикаций посвящено ANCA-ассоциированному ГН, который развился у пациентов с торпидным течением и высокой степенью активности полиартикулярной и системной форм ЮРА. Особенностью ANCA-ассоциированного ГН явилось наличие гиперкреатининемии и практически в половине случаев— развитие терминальной почечной недостаточности, несмотря на проводимую иммунодепрессивную терапию. Единичные случаи других вариантов ГН описаны более 10 лет назад. Клинически отмечались протеинурия и реже— нефротический синдром, что стало основанием для прижизненного морфологического исследования почек. Иммунодепрессивная терапия была эффективной при мезангиопролиферативном ГН и болезни минимальных изменений. Во всех случаях при фокально-сегментарном гломерулосклерозе, экстракапиллярном ГН отмечено формирование терминальной почечной недостаточности. Благоприятный прогноз оказался у детей с мембранозной нефропатией, индуцированной препаратами, после отмены последних. Представлены публикации с положительным терапевтическим эффектом применения генно-инженерных биологических препаратов при ANCA-ассоциированном ГН, IgМ-нефропатии, гормонорезистентном варианте болезни минимальных изменений у детей с ЮРА.

Markers of genomic instability in patients with juvenile rheumatoid arthritis

Research purpose. To determine the state of the genome instability in patients with juvenile rheumatoid arthritis and to assess its dependence on biological (age and sex) and clinical (form and variant of the flow of juvenile rheumatoid arthritis, its activity, duration, functional class and serotype of the patient) parameters.Material and methods: 95 children were surveyed. Among them, 68 (39 girls and 29 boys) – with various forms of juvenile rheumatoid arthritis, 12 – without treatment (at the stage of verification of the diagnosis). The control group consisted of 15 conditionally healthy children aged 3 to 16 years. To assess the genome instability, the method of determination of micronuclei in peripheral blood binuclear lymphocytes under the conditions of a cytochalasin block (in vitro) was used.Results: All examined children in the active form of the disease showed a significant increase in the level of binuclear lymphocytes with micronuclei in lymphocytes compared with a group of conditionally healthy children. The maximum values of this indicator were observed in the age group from 5 to 10 years and in children with a disease duration of up to 1 year. As the activity of the process increases, the level of binuclear lymphocytes with micronuclei rises. After treatment, a significant decrease in the indicator content was detected in patients with the II degree of disease activity in both cases of juvenile rheumatoid arthritis.Conclusion. Statistically significant increase in the level of binuclear lymphocytes with micronuclei in peripheral blood lymphocytes may indicate the formation of genome instability in children as a pathogenetic part in juvenile rheumatoid arthritis.

Иммуногенетические показатели как маркеры агрессивного течения и эффективности базисной терапии при ревматоидном артрите у детей

The immunological and immunogenetic features of juvenile rheumatoid arthritis in the Kyrgyz population are studied for the first time. The study was conducted in 30 healthy children and 67 patients aged 3 to 16 years. The method of rosette formation was used. Associative links were established in the systemic form of juvenile rheumatoid arthritis with histocompatibility antigens in the HLA Cw5, B12 system, and the B15, A2, A9 antigens with high activity of the process, early development of bone and cartilage destruction and functional impairments. In the first 6 months of disease, it recommended the appointment of an aggressive baseline therapy.

VITAMIN D AND ITS ROLE IN COURSE OF INFLAMMATORY DISEASES OF JOINTS IN CHILDREN

Studies of recent decades have found that vitamin D implements immunoregulatory effects by influence on mechanisms of nonspecific protection from infectious agents, as well as on a system of a specific immune response. A number of studies indicate a relationschip between vitamin D deficiency and the autoimmune diseases onset.Objective. To improve diagnosis of juvenile rheumatoid arthritis and reactive arthritis in children by studying of the serum 25-hydroxyvitamin D impact on disease activity. Materials and methods. 80 children aged 2 to 16 years were observed. I group included 20 children with articular form of juvenile rheumatoid arthritis (JRA), II group - 40 children with reactive arthritis (RA). The control group consisted of 20 healthy children. To all children level of serum 25-hydroxyvitamin D was measured by enzyme immunoassay.Results. A significant 25-hydroxyvitamin D decrease was found among children with JRA 19.53 [12.34;27.50] mmol/L and RA 22.77 [12.39;36.33] in comparison with the children of control group 27.08 [19.87;50.90] mmol/l (p<0,05). Inverse correlation was found between serum 25-hydroxyvitamin D and number of affected joints in children with JRA (p<0,02), as well as between 25-hydroxyvitamin D and indicators of laboratory activity in RA and JRA patients (p<0,05).Conclusion. This study indicates a reliable relationship between the disease аctivity and serum 25-hydroxyvitamin in reactive arthritis and juvenile rheumatoid arthritis patients. Thus, serum 25-hydroxyvitamin D can be used as a marker of disease severity, as well as for predicting the course of inflammatory joint disease in children.

СТАН СПОЛУЧНОЇ ТКАНИНИ В ДІТЕЙ, ХВОРИХ НА РЕАКТИВНИЙ АРТРИТ ТА ЮВЕНІЛЬНИЙ РЕВМАТОЇДНИЙ АР- ТРИТ.

У статті наведено клінічні та лабораторні показники стану сполучної тканини в дітей, хворих на реактивний артрит та суглобову форму ювенільного ревматоїдного артриту. Отримані дані дають можливість стверджувати, що в дітей, хворих на вказані запальні захворювання суглобів, частіше виявляється дисплазія сполучної тканини порівняно зі здоровим дітьми, що має також лабораторне відображення у вигляді зниження рівнів глікозаміногліканів в обох обстежених групах.

CLINICAL AND ECONOMIC ANALYSIS OF ETANERCEPT EFFICACY IN A PATIENT WITH JUVENILE HEUMATOID ARTHRITIS

Article contains clinical and economic analysis of treatment efficacy of a patient with a poliarticular form of juvenile rheumatoid arthritis (JRA) with soluble TNF receptors — etanercept. Such methods of analysis as «disease value» and «expense–efficacy» were used. It has been shown that «disease value» increases against the background of etarnecept use. However, further analysis has shown that from the «expense–efficacy» point etarnecept use decreases expenses in 6.3 times (both direct and indirect expenses, in 4.3 times using only direct expenses) in comparison to standard antirheumatic treatment, that lays economic grounds for etarnecept use for patients with refractory JRA.

Characterisation of complex chromosome 18p rearrangements in two syndromic patients with immunological deficits

There have been reports that a number of patients with a chromosome 18pter deletion have developed autoimmune disorders, including juvenile diabetes, rheumatoid arthritis, thyroiditis and Graves’ disease, and/or show little or no reduction in serum IgA levels. We describe two female patients bearing complex rearrangements involving chromosome 18p. Array-CGH and BAC FISH molecular cytogenetic analyses enabled the precise identification of the affected 18p region. One patient has a 2 Mb terminal deletion associated with a 9.2 Mb inverted duplication of the adjacent region; the other has a more extended 10.1 Mb terminal deletion associated with a 4.1 Mb quadruplication of the adjacent region and a 2.6 Mb duplication of the pericentromeric region. Both patients have dysmorphic features typical of 18p deletion syndrome, such as growth retardation, epicanthal folds, a long philtrum and toe defects, and are also affected by immunological disorders. One has a form of immunological deficiency that takes the form of recurrent pulmonary infections and low IgA levels; the other has an autoimmune form of juvenile rheumatoid arthritis. Relating the refined molecular cytogenetic characterisation of these 18p chromosomal rearrangements to the patients’ specific clinical characteristics can improve our understanding of the role of the 18p region in immune responses.

Still's disease can cause neutrophilic meningitis.

Still’s disease is a rare disorder that occurs in both children and adults. It is designated as the systemic form of juvenile rheumatoid arthritis (JRA) in children younger than 16 years, and is called adult-onset Still’s disease (AOSD) in older patients. It is characterized by high fever, a salmon-colored skin rash, arthritis or arthralgias, and a markedly increased leukocyte count. It may be accompanied by sore throat, splenomegaly, or lymphadenopathies. Although involvement of the heart, lungs, liver, and gastrointestinal tract has been reported, neurologic involvement is unusual. We report five episodes of acute neutrophilic meningitis occurring in four female patients with Still’s disease. Diagnoses of systemic onset JRA (Patients 1 to 3) and AOSD (Patient 4) were based on the presence of the four major Reginato criteria.1 Patients 1, 2, and 4 exhibited persistent or intermittent fever, an evanescent erythematous maculopapular rash, poly- or oligoarthritis, and neutrophilic leukocytosis. Patient 3 satisfied only three major criteria (no rash), …

Juvenile rheumatoid arthritis.

1. Jane G. Schaller, MD* 1. 2. *David and Leona Karp Professor of Pediatrics; Chair, Department of Pediatrics, Tufts University School of Medicine, Boston, MA. 1. There are several recognizable subgroups of juvenile rheumatoid arthritis (JRA): systemic-onset, polyarticular, pauciarticular, and late childhood onset. 2. Rheumatoid factor usually is negative in JRA. 3. Systemic-onset JRA is characterized by high intermittent fevers and other extra-articular manifestations: lymphadenopathy, rash, pleuritis, and pericarditis. 4. Iridocyclitis is absent in acute-onset disease but common in patients who have pauciarticular disease. 5. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the front-line and important agents in the therapy of patients who have JRA. 6. Controlled studies show that d-penicillamine, hydroxychloroquine, and oral gold are no more effective than placebo in the treatment of JRA. Juvenile rheumatoid arthritis (JRA) is a term used to describe the condition of chronic synovitis in children of which there are several distinct subgroups. Chronic synovitis in children was first described well in the English literature in 1897 by George Frederick Still, an English pediatrician and pathologist, who reported on 23 children who had chronic arthritis and came to his attention while he was training at the Hospital for Sick Children, Great Ormond Street. Still postulated that several separate conditions were responsible for chronic arthritis in children. Little subsequent work in this area was pursued until the late 1940s. Most modern observers have come to agree with Still that chronic arthritis in children encompasses several distinct disease subgroups (Table 1⇓ ). The relationship of JRA to adult rheumatoid arthritis was uncertain for many years. Now it seems clear that the classic adult-type rheumatoid arthritis does occur in children but is quite rare, the JRA subgroups seronegative 1 polyarthritis and systemic-onset disease also occur in adults but not frequently, the pauciarthritis of early childhood has not been recognized in adults, and the pauciarthritis of older children usually is classified as spondyloarthropathy in adults. The nomenclature for chronic childhood arthritis remains confusing (Table 2⇓), but …

Identification of childhood arthritis in archaeological material: juvenile rheumatoid arthritis versus juvenile spondyloarthropathy.

The opportunity to examine the defleshed skeleton of an individual diagnosed in life (Hamann-Todd collection, individual 2036) afforded a unique opportunity to demonstrate the bone damage characteristic of at least one form of juvenile rheumatoid arthritis (JRA). Characteristics helpful for recognition of JRA in archaeological material include peripheral articular marginal and subchondral erosions, axial (e.g., zygapophyseal or sacroiliac) joint erosions, fusion of axial (cervical zygapophyseal) and/or peripheral joints, premature epiphyseal closure and/or ballooned epiphyses, growth retardation with underdeveloped (short and overtubulated) long bones, short mandibular rami with underdeveloped condyles and concomitant micrognathia, and demineralization (osteopenia). Distinguishing between JRA and juvenile spondyloarthropathy, however, is not always possible, as illustrated by this case.

Identification of childhood arthritis in archaeological material: Juvenile rheumatoid arthritis versus juvenile spondyloarthropathy

The opportunity to examine the defleshed skeleton of an individual diagnosed in life (Hamann-Todd collection, individual 2036) afforded a unique opportunity to demonstrate the bone damage characteristic of at least one form of juvenile rheumatoid arthritis (JRA). Characteristics helpful for recognition of JRA in archaeological material include peripheral articular marginal and subchondral erosions, axial (e.g., zygapophyseal or sacroiliac) joint erosions, fusion of axial (cervical zygapophyseal) and/or peripheral joints, premature epiphyseal closure and/or ballooned epiphyses, growth retardation with underdeveloped (short and overtubulated) long bones, short mandibular rami with underdeveloped condyles and concomitant micrognathia, and demineralization (osteopenia). Distinguishing between JRA and juvenile spondyloarthropathy, however, is not always possible, as illustrated by this case. Am J Phys Anthropol 102:249–264, 1997 © 1997 Wiley-Liss, Inc.

The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue.

We document here the identification of germinal centres with dark and light zones, a follicular dendritic cell network and clonal expansion in the synovium of rheumatoid arthritis patients. Synovial tissue from 24 patients suffering from rheumatoid arthritis or the polyarticular form of juvenile rheumatoid arthritis were screened for the presence of lymphoid follicles. The synovial tissues of 14 patients contained follicles and four of these had germinal centres and a follicular dendritic cell network. There was a statistically significant association between follicles in the synovium and the presence of rheumatoid factor autoantibodies in the patients' serum indicating a link between local germinal centre formation and the presence of pathological rheumatoid factors. Nucleotide sequencing of monoclonal rheumatoid factors from one of the patients' synovial tissue which contained germinal centres clearly supports the possibility that these rheumatoid factors have gone through a germinal centre reaction. While rheumatoid factors from healthy immunized donors are regulated through a tolerization mechanism which selects against replacement mutations and does not allow affinity maturation, synovial rheumatoid factors seem to lack this tolerization mechanism. The formation of germinal centres where B cells affinity mature and expand at the central site of disease in rheumatoid arthritis may explain why rheumatoid factors in rheumatoid arthritis develop into auto-aggressive antibodies.

Mandibular condyle lesions related to age at onset and subtypes of juvenile rheumatoid arthritis in 15‐year‐old children

The severity of lesions in the temporomandibular joint (TMJ) area and their association with age at onset, the various forms of juvenile rheumatoid arthritis (JRA), and certain serologic tests for rheumatoid factor (RF), antinuclear antibodies (ANA), and human leukocyte antigen (HLA)-B27 were determined in 15-yr-old children. The series comprised 121 JRA children, 78 girls and 43 boys, in whom an analysis had recently been made of the relation of TMJ lesions to jaw movement and occlusal status. The mean age at onset was 7.3 yr, the girls contracting JRA earlier than the boys. Also, the girls with lesions in the TMJ area were significantly younger than those with no lesions. TMJ abnormalities were found in 50% of cases with a pauciarticular or systemic onset, but in 72% of those representing the polyarticular subtype. Flattened condyles and grave lesions were equally represented in all subgroups and in both sexes. A crossover from onset type to present diagnosis was found in 30% of the cases, mostly from pauciarticular to polyarthritis, which also increased the risk of TMJ lesions from 50 to 60%. RF, ANA, or HLA-B27 alone did not seem to be associated with a risk of TMJ abnormalities. Maximal opening capacity is more restricted in patients with early onset or a polyarticular mode of JRA. Since the TMJ is affected in more than half of JRA children, regular measurements of maximal movements of the mandible or roentgenologic examinations of the TMJ are essential for their optimal treatment.

Human Monoclonal IgG Rheumatoid Factors from the Synovial Tissue of Patients with Rheumatoid Arthritis

We have established IgG rheumatoid factor (RF)-secreting hybridoma cell lines from the synovial tissues of two patients (TS and SJ) with rheumatoid arthritis (RA) and one (KL) with the polyarticular form of juvenile rheumatoid arthritis (JRA). The IgG RF bind human and rabbit IgG and all except one form intracellular complement-fixing complexes indicative of a self-association process. The possibility of IgG RF for self association and immune complex formation is a feature thought to be important for the inflammatory processes in RA. Of the IgG RF-secreting cell lines established, three clones from patient SJ and one from patient KL are of the IgG1 kappa isotype while five clones from patient TS are of the IgG2 lambda isotype.

Human leukocyte antigen-DRB1 *1104 in the chronic iridocyclitis of pauciarticular juvenile rheumatoid arthritis

To determine whether genetic markers for chronic iridocyclitis could be identified, we used both serologic and oligonucleotide dot blot techniques to characterize immunogenetically 164 children with early-onset pauciarticular juvenile rheumatoid arthritis. Seventy-eight children (47.6%) had chronic iridocyclitis and 86 (52.4%) had not had evidence of eye disease during a mean follow-up period after the onset of arthritis of 15.8 years (minimum of 5.5 years). Control subjects were 218 healthy, unrelated individuals. The analysis was limited to alleles known to be associated with an increased or decreased risk of early-onset pauciarticular juvenile rheumatoid arthritis or of chronic iridocyclitis in this form of juvenile rheumatoid arthritis. Only one split of human leukocyte antigen (HLA)-DR5, HLA-DRB1* 1104, showed a statistically significant association with a risk of chronic iridocyclitis (chi-square value = 7.52; p = 0.036 adjusted; odds ratio 3.45); HLA-DQA1* 0501 and HLA-DQB1* 0301, both in linkage disequilibrium with HLA-DRB1* 1104, also were significantly associated with eye disease. Patients with both the DRB1* 1104 and DPB1* 0201 genes had a 7.7-fold increased risk for chronic iridocyclitis compared with that for other patients. The presence of HLA-DRB1* 1104 was about four times as specific, but only about one third as sensitive, as antinuclear antibodies in identifying patients at risk for eye disease. Although all children with early-onset pauciarticular juvenile rheumatoid arthritis should undergo periodic slit-lamp examinations, those with the HLA class II gene DRB1* 1104 are at particularly high risk for eye disease, and we recommend that they be monitored carefully for its evolution.

Polymorphism in a T-cell receptor variable gene is associated with susceptibility to a juvenile rheumatoid arthritis subset.

This report demonstrates a T-cell receptor (Tcr) restriction fragment length polymorphism, defined by a Tcrb-V6.1 gene probe and Bgl II restriction enzyme, to be absolutely correlated with allelic variation in the coding sequence of a Tcrb-V6.1 gene. A pair of non-conservative amino acid substitutions distinguish the Tcrb-V6.1 allelic variants. An association of this Tcrb-V6.1 gene allelic variant with one form of juvenile rheumatoid arthritis (JRA) was established in a cohort of 126 patients. The association was observed in patients possessing the HLA-DQA1*0101 gene. Among HLA-DQA*0101 individuals, 19 of 26 patients (73.1%) carried one particular Tcrb-V6.1 gene allele as opposed to 11 of 33 controls (33%; p less than 0.005). Haplotypes carrying this HLA gene have previously been shown to confer increased risk for progression of arthritis in JRA. This demonstration of a disease-associated Tcrb-V gene allelic variant has not, to our knowledge, been previously reported and supports the contribution of polymorphism in the Tcr variable region genomic repertoire to human autoimmune disease.

The Immunogenetics of Juvenile Rheumatoid Arthritis

Recent major advances in understanding the genetic structure of the human leukocyte antigen (HLA) region and how HLA molecules contribute to immune responses have been paralleled by more precise identification of specific HLA genes conferring susceptibility to the various forms of juvenile rheumatoid arthritis (JRA). This article presents current models for HLA-associated autoimmune disease susceptibility and summarizes the HLA Class II alleles currently known to be associated with JRA: primarily DR8, DR5, DR6, and DPw2.1 in pauciarticular onset JRA; and DR4 in rheumatoid factor-positive polyarticular onset JRA. Rheumatoid factor-negative polyarticular onset JRA and systemic onset JRA are variously associated with several of these same genes. Gene interactions and the clinical utility of HLA typing in this disease are also discussed.

Magnetic resonance imaging of articular destruction in juvenile rheumatoid arthritis

We describe herein magnetic resonance imaging of the right knee of a patient affected by a severe form of juvenile rheumatoid arthritis. Magnetic resonance imaging findings of articular damage of the knee during the disease course and after arthroscopic synovectomy are described.

Cellular immunity in patients with systemic juvenile rheumatoid arthritis

We studied the cellular immune responses in 10 patients with systemic form of juvenile rheumatoid arthritis. The numbers of peripheral T lymphocytes and their helper/inducer and cytotoxic/suppressor subpopulation were within normal levels. Activated T lymphocytes (DR +) were slightly increased but not at statistically significant levels. In contrast to the T cells, B lymphocytes were increased; both the percentage of B cells (B1 +) and the number of cells spontaneously secreting IgG, IgA, and IgM were increased. Stimulation of periphral mononuclear cells in vitro with pokeweed mitogen induced poor plaque-forming cell responses, which were partially improved upon removal of monocytes. The presence of concanavalin A in the cultures led to complete suppression. We conclude that patients with systemic JRA are characterized primarily by B-cell rather than T-cell abnormalities.