Polyarticular-onset Juvenile Rheumatoid Arthritis Research Articles

Is measurement of IgM and IgA rheumatoid factors (RF) in juvenile rheumatoid arthritis clinically useful?

The prevalence and clinical relevance of IgM and IgA RF detected by ELISA were studied in 91 patients with juvenile rheumatoid arthritis (JRA) and 45 healthy children. IgM and IgA RF were detected, respectively, in 33 and 44% of the patients, compared to 6.7 and 15.6% of the healthy children (p = 0.001 and 0.0006, respectively). The frequency of IgM RF was significantly higher in patients with polyarticular (52%) as compared to systemic onset JRA (21%; p = 0.04). Five out of ninety-one patients and none of the control group were IgM RF positive by the latex test. High levels of IgM RF were detected more frequently in patients with active disease (p = 0.01) and positive latex agglutination test (p < 0.001) and had a marginally significant association with severe radiological deformities (p = 0.05). The presence of IgA RF was associated with active disease in polyarticular onset JRA children (p = 0.04). In conclusion, high levels of IgM RF and the detection of IgA RF can be useful in assessing clinical activity in a subset of patients with JRA.

Antibodies against cyclic citrullinated peptide are associated with HLA–DR4 in simplex and multiplex polyarticular‐onset juvenile rheumatoid arthritis

Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile rheumatoid arthritis (JRA), particularly in those with polyarticular, rheumatoid factor (RF)-positive JRA. Our objectives were to determine whether anti-CCP antibodies are associated with HLA-DR4 in children with polyarticular JRA, whether anti-CCP antibodies are associated with clinical features of disease, and whether affected sibling pairs (ASPs) with JRA are concordant for this antibody. Stored serum samples obtained from 230 HLA-typed patients with JRA (77 with polyarticular-onset disease and 153 with pauciarticular- or systemic-onset disease), 100 JRA ASPs, and 688 healthy children were tested for anti-CCP antibodies and RF. Thirteen percent of the patients with polyarticular-onset JRA and 2% of the other JRA patients exhibited anti-CCP antibodies, compared with only 0.6% of the controls. Fifty-seven percent of RF-positive patients with polyarticular-onset JRA had anti-CCP antibodies. HLA-DR4-positive patients with polyarticular-onset JRA were more likely to have anti-CCP antibodies than were those without HLA-DR4 alleles (odds ratio [OR] 5.20, 95% confidence interval [95% CI] 1.30-20.9). Anti-CCP antibodies were associated with polyarticular onset (OR 7.46, 95% CI 1.99-28.0), a polyarticular disease course (OR 9.78, 95% CI 1.25-76.7), and erosive disease (OR 14.3, 95% CI 3.01-67.9). Concordance rates for anti-CCP antibodies among ASPs were statistically significant. These data demonstrate increased anti-CCP antibody formation in HLA-DR4-positive patients with polyarticular-onset JRA. The overall prevalence of anti-CCP antibodies in JRA is low, but a substantial proportion of RF-positive patients with polyarticular-onset JRA have these antibodies. Anti-CCP antibodies in JRA are associated with polyarticular onset, a polyarticular course, and erosive disease.

Current Medication Choices in Juvenile Rheumatoid Arthritis II –Update of a Survey Performed in 1993

The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is important to allow for the evaluation of practice patterns for future outcome studies. A survey of nine pediatric rheumatologists was performed between September 1999 and February 2000. Each of the physicians prospectively recorded demographic and treatment information on consecutively sampled JRA patients (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in 35%, and systemic onset JRA in 19% of the children. Naproxen was the most frequently prescribed medication (55% of the patients), followed by methotrexate (MTX), which was used in 39% of the patients. Folic acid supplementation (1 mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used in 11% of the children. Eleven percent of the patients received corticosteroids, and 13% of children on corticosteroids took calcium supplements. Uveitis was present in 8% and had a chronic course in 79% of those cases. Although systemic medications were used in 50% of the children with uveitis to control eye inflammation, severe damage to the eyes developed in 30% of them. Fourteen percent of the patients required gastroprotective medications. Compared with findings of a similar survey performed in 1993, there was no significant change in the frequency of use of naproxen, but nabumetone is now more often prescribed, and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among second-line agents used for JRA have also occurred, although there was no change in the frequency of use of MTX or corticosteroids. JRA continues to be a treatment challenge for the practicing pediatric rheumatologist. Patients often show incomplete response to the currently available medications. Therefore, new therapeutic agents need to be evaluated for their use in JRA, and the treatment of JRA associated uveitis especially needs to be improved.

Antibodies against a peptide sequence located in the linker region of the HMG-1/2 box domains in sera from patients with juvenile rheumatoid arthritis.

To extend our work on the mapping of B cell epitopes on nucleosomal high mobility group (HMG) proteins in the sera of patients with juvenile rheumatoid arthritis (JRA). Seventy-seven pauciarticular-onset JRA serum samples from antinuclear antibody (ANA)-positive patients and 42 polyarticular-onset JRA patient sera found to react with HMG-2 by immunoblotting were used in this study. To identify B cell epitopes on HMG-2, recombinant HMG-2 protein fragments were used in enzyme-linked immunosorbent assay (ELISA) and in competition ELISA experiments with a set of overlapping synthetic peptides. Fine epitope mapping was achieved by oligopeptide synthesis, followed by immunoblotting. Pauciarticular, but not polyarticular, JRA patient sera were found to recognize a lysine-rich major epitope (KKGKKKDP), which is located in the linker region of the HMG box domains of the HMG-2 nonhistone chromosomal protein. No significant immunoreactions were observed in sera from ANA-negative JRA patients and in sera from children with nonrheumatic diseases, indicating that this epitope seems to be specific for pauciarticular-onset JRA. In addition to our previous finding that JRA sera will react with a defined epitope on HMG-17, pauciarticular JRA patient sera were also found to recognize a defined epitope on the HMG-2 protein, thus suggesting the importance of this epitope in the etiology of JRA.

Accelerated nodulosis during methotrexate therapy for juvenile rheumatoid arthritis

We describe two patients with rheumatoid factor-positive, polyarticular-onset juvenile rheumatoid arthritis in whom accelerated nodulosis developed during methotrexate therapy. Although they had only a few nodules at diagnosis, the nodules increased in number and size 3 to 4 months after the start of methotrexate therapy in both patients. The nodules regressed after withdrawal of methotrexate therapy in one patient and were arrested with the addition of hydroxychloroquine in the other. Physicians treating patients with methotrexate for juvenile rheumatoid arthritis must be aware of this extraarticular side effect.

Syndrome of Camptodactyly, Arthropathy and Coxa Vara (Cac Syndrome)

Three Saudi children (two female, one male) are described who presented with familial arthropathy associated with congenital camptodactyly. This rare but recognized clinical entity has a variable clinical presentation and may be associated with pericarditis and coxa vara. Camptodactyly was observed in the neonatal period in all patients, while joint swelling was observed between the third and 11th month. Pericarditis was suspected in the referral hospital in one patient but was not subsequently confirmed at our institution, raising the possibility that pericarditis may be reversible. Radiological examination of the hips showed coxa vara with short femoral neck in all patients. Synovial biopsy in the three patients revealed proliferating synovial epithelium with moderate fibrocollagenous densities and multinucleated giant cells, occasional lymphocytes or neutrophils but no plasma cells were identified. This is the first series of this familial arthropathy with a triad of camptodactyly, arthropathy and coxa vara (CAC syndrome) in Saudi Arabia which is to be considered in patients where more than one family member has juvenile arthritis.

Autoantibodies to the chromosomal protein HMG-17 in juvenile rheumatoid arthritis.

To determine the antibody profiles in sera from patients with juvenile rheumatoid arthritis (JRA). Immunoblotting using nuclear extracts and recombinant high-mobility group (HMG) nonhistone chromosomal proteins. Antibodies directed against HMG-17 were found in 47% of antinuclear antibody (ANA)-positive patients with pauciarticular-onset JRA and in 16% of ANA-positive patients with polyarticular-onset JRA. HMG-17 values of 6% and 8%, respectively, were detected in ANA-negative patients with JRA and in those with nonrheumatic diseases. There is evidence for a high prevalence of anti-HMG-17 antibodies in sera of patients with pauciarticular-onset JRA.

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.

Autoantibodies to nonhistone chromosomal proteins HMG‐1 and HMG‐2 in sera of patients with juvenile rheumatoid arthritis

IgG antibodies against the high mobility group (HMG) nonhistone chromosomal proteins HMG-1 and/or HMG-2 were detected in the sera of 49 (39%) of 126 antinuclear antibody (ANA)-positive patients with juvenile rheumatoid arthritis (JRA), by immunoblotting. Clinical diagnosis classified these patients in 2 major groups, 105 with pauciarticular-onset JRA and 21 with polyarticular-onset JRA. Anti-HMG-1 and/or anti-HMG-2 antibodies were found in 8 (25%) of 32 pauciarticular-onset JRA patients with uveitis and in 34 (47%) of 73 patients without uveitis, whereas anti-HMG-1 and/or anti-HMG-2 antibodies were found in 4 (24%) of 17 children with polyarticular-onset JRA without uveitis. Among 53 sera from ANA-negative JRA patients, 3 (6%) were positive for anti-HMG-1 and/or anti-HMG-2 antibodies, whereas no reactivity to HMG-1 or HMG-2 proteins was observed in 48 sera from age-matched children with nonrheumatic diseases.

The timing of menarche in juvenile rheumatoid arthritis

A study of the age of menarche in juvenile rheumatoid arthritis (JRA) patients was undertaken to determine what factors affect the timing of menarche. There was a significant difference between the mean age of menarche for the 68 JRA patients and 46 controls (p = 0.015). No clear etiology for this difference was elucidated. Polyarticular-onset JRA patients had the oldest age of menarche, but this finding was of marginal statistical significance (p less than 0.05,pcorr less than 0.25). The multivariate model that included onset type, steroid use, and duration of disease weakly predicted age of menarche in the JRA group. This model suggests that, exclusive of height and weight parameters, duration of disease was the most important predictor of menarche in JRA.

19S IgM rheumatoid factor-7S IgG rheumatoid factor immune complexes isolated in sera of patients with juvenile rheumatoid arthritis.

19S IgM rheumatoid factors (RF) and hidden 19S IgM RF have been associated with increased disease activity in juvenile rheumatoid arthritis (JRA). Recently, immune complexes (IC) were isolated from JRA sera by several methods which demonstrated the presence of 19S IgM RF. The present study evaluates 25 JRA patients' sera by separation on a Sepharose 4B column to which were bound F(ab')2 fragments of goat IgG antihuman IgM antibody to separate IgM-containing IC. The columns were sequentially eluted with 1 M ammonia and 0.1 M glycine-HCl buffer, pH 3.0. The isolated fractions were assayed for 19S IgM RF and 7S IgM RF by ELISA, IgG levels by immunodiffusion, and by preparative isoelectric focusing. The ammonia eluate from the alpha HIgM column revealed IgG, 19S IgM RF in six patients, and IgM RF in four patients. All were polyarticular-onset JRA patients. In the glycine-HCl eluate of sera, 19S IgM RF and IgG were also detected in 15 patients, all six seropositive, polyarticular-onset, six seronegative, polyarticular-onset, and three pauciarticular-onset patients. Significant 7S IgG RF titers were demonstrated in the glycine-HCl eluates of six patients, five seropositive, polyarticular-onset patients, and one seronegative, polyarticular-onset patient. Analysis by preparative isoelectric focusing of the IgM RF and IgG RF positive ammonia and glycine-HCl eluates showed IgM RF throughout the pH range (4-10), but the highest amount of IgM RF was in the pH range 4.0-5.5. Significant IgG RF titers were detected only in this restricted spectrotypic area of pH 4.0-5.5.(ABSTRACT TRUNCATED AT 250 WORDS)