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PubMed1986

Similar survival rates for rheumatoid and non-rheumatoid cancer patients.

The survival rate for cancer patients with rheumatoid arthritis was compared with that for non-rheumatoid cancer patients. This was accomplished by linking two nationwide Finnish data registers, the Social Insurance Institution's Population Register and the Finnish Cancer Registry. For 2012 of the 2062 rheumatoid patients with cancer diagnosed after the diagnosis of rheumatoid arthritis, the Cancer Registry was successfully searched for a non-rheumatoid of diagnosis of control patient who matched with respect to sex, age, year of diagnosis of cancer and location of the tumour (and also, for leukaemia, with respect to cell type). The 5-year relative survival rate for male rheumatoid patients was 21.2% and, for the control cancer patients, 25.4%. In females, the corresponding rates were 38.2% for the rheumatoid patients and 41.2% for the control patients (p less than 0.05). At some sites, particularly with leukaemia, the rates for the rheumatoid patients were lower than those for the control patients. The difference, however, only reached a 5% significance level for colorectal cancer in males. Rheumatoid arthritis and its treatment do not seem to have any appreciable effect on the survival of cancer patients.

Arthritis, Rheumatoid↗
PubMed2002

[The rheumatoid vasculitis and malignant rheumatoid arthritis(MRA)].

The inflammatory process characteristic of rheumatoid arthritis is typically targeted to the synovial membrane. In a subset of patients, rheumatoid disease is complicated by an inflammatory destruction of blood vessels, rheumatoid vasculitis. Rheumatoid vasculitis has been understood to be the result of severe disease extending beyond the joint, possibly caused by immune complex deposition. However, in Japan malignant rheumatoid arthritis(MRA) is designated as rheumatoid arthritis with vasculitis. Rheumatoid arthritis patients can be separated into two groups: individuals with synovial disease and individuals with synovial plus extra-articular disease, MRA. The model is supported by immunogenetic analysis describing an accumulation of vasculitis patients with rheumatoid arthritis among HLA-DRB10401 homozygotes. Therapy depends upon the clinical manifestation of rheumatoid vasculitis. Then, MRA is usually treated with steroid, and steroid pulse therapy and immunosuppressants are useful for severe MRA.

Arthritis, Rheumatoid↗
PubMed2000

Treatment with leflunomide slows radiographic progression of rheumatoid arthritis: results from three randomized controlled trials of leflunomide in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group.

OBJECTIVE: To determine whether treatment with leflunomide (LEF), methotrexate (MTX), or sulfasalazine (SSZ) for 6-12 months retards progression of radiographic damage and to identify clinical variables that correlate with radiographic progression. METHODS: Radiographs of the hands and feet were performed at baseline and at the end of study or early exit in 3 randomized controlled trials. Protocol US301 was a 12-month controlled trial of LEF or MTX treatment compared with placebo in 482 patients randomized in a 3:3:2 ratio. Protocol MN301 compared 6 months of LEF or SSZ treatment with placebo in 358 patients, randomized in a 3:3:2 ratio, with continued blinded treatment in the active control arms for 12 months. Protocol MN302 compared 12 months of LEF treatment with MTX in 999 patients. Radiographs were blinded for sequence and treatment and were scored for erosions and joint space narrowing. All analyses were by intent-to-treat. Sensitivity analyses were performed to account for missing data. RESULTS: LEF, MTX, and SSZ treatment resulted in statistically significantly less radiographic progression compared with placebo at 6 and 12 months: for protocol US301, LEF versus placebo P = 0.0007 and MTX versus placebo P = 0.0196; for protocol MN301, LEF versus placebo P = 0.0004 and SSZ versus placebo P = 0.0484. The effect of LEF treatment was similar to that of MTX and SSZ. CONCLUSION: These are the first 6- and 12-month randomized placebo- and active drug-controlled trials to demonstrate retardation of radiographic progression by a new disease-modifying antirheumatic drug (DMARD), LEF, as well as 2 commonly used DMARDs, MTX and SSZ.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Penicillamine for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline up to and including December 1998 and Embase from 1988-1998. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials and controlled clinical trials comparing D-penicillamine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found. MAIN RESULTS: Six trials were identified, with 425 patients randomized to D-penacillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0. 51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0. 87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities. REVIEWER'S CONCLUSIONS: D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.

Antirheumatic Agents↗
PubMed2004

Rheumatoid arthritis with diffuse pulmonary rheumatoid nodules.

Rheumatoid nodules in dermal or subcutaneous tissues, while indicative of rheumatoid arthritis, are very rare. It is even less common to identify these rheumatoid nodules by biopsy as well as in autopsy materials from lung tissue. These nodules may be single or multiple, which seldom cause respiratory symptoms. Here, a patient with diffuse pulmonary rheumatoid nodules and interstitial fibrosis throughout both lungs, is described. The patient, with articular symptoms and seropositivity, exhibited a rapid clinical course and died of respiratory failure 3 months after the appearance of dyspnea. Chest radiography indicated interstitial pneumonitis with bilateral diffuse peripheral shadows. At autopsy, numerous rheumatoid nodules and interstitial fibrosis had destroyed both lungs, such that no residual normal pulmonary tissue remained. It is believed that this was an extremely rare case exhibiting large numbers of rheumatoid nodules throughout the lungs. Findings with this patient indicate that, in patients with rheumatoid arthritis, clinical interstitial pneumonitis confirmed radiologically does not exclude the existence of rheumatoid lung nodules.

Arthritis, Rheumatoid↗
PubMed2004

Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis.

OBJECTIVE: To assess the additional diagnostic and clinical value of the second test generation of anti-cyclic citrullinated peptide antibodies (CCP2) compared with rheumatoid factor isotypes (IgG-RF, IgA-RF, IgM-RF) in patients with rheumatoid arthritis. METHODS: This was a prospective study on 715 patients: rheumatoid arthritis (n = 295), degenerative or other inflammatory joint disease (n = 163), connective tissue disease or vasculitis (n = 103), and healthy controls (n = 154). Sera from each subject were tested for CCP2 and RF isotypes by enzyme linked immunosorbent assay (ELISA). Agreement with clinical indices such as disease activity, joint destruction, disease duration, and other laboratory tests was assessed. Sensitivity and specificity of the tests were evaluated taking the clinical diagnosis as the gold standard. RESULTS: Highest sensitivity was found for IgM-RF (66.4%) and CCP (64.4%). Highest specificity was achieved by CCP (97.1%) and IgG-RF (91.0%). In rheumatoid patients with high disease activity or severe joint damage, CCP was more often present (81.4% and 83.6%) than all RF isotypes. Of special diagnostic value was the detection of positive CCP in 34.5% of all patients with rheumatoid arthritis when all measured RF isotypes (IgG-RF, IgA-RF, and IgM-RF) were negative. CONCLUSIONS: As a screening method for rheumatoid arthritis the IgM-RF and the CCP assays are superior to other RF isotypes. Positivity in the highly specific CCP ELISA supports the diagnosis of rheumatoid arthritis. CCP proved to be a powerful diagnostic tool, especially in ambiguous cases or RF negative patients with rheumatoid arthritis.

Adult↗
PubMed1980

Circulating and intra-articular immune complexes in rheumatoid arthritis: a comparative study of the C1q binding and monoclonal rheumatoid factor assays.

The C1q binding assay and the nephelometric monoclonal rheumatoid factor assay were able to discriminate 79% and 57% respectively of rheumatoid arthritis (RA) patients from healthy blood donors. In addition these assays could distinguish those patients with active arthritis from those with inactive disease, and the C1q binding assay correlated significantly with other laboratory indices of the rheumatoid process, including the erythrocyte sedimentation rate, low molecular weight or 7S IgM, and the rheumatoid factor titre. High levels of C1q binding were also seen in rheumatoid vasculitis. Both assays gave higher mean values in synovial fluid compared with the corresponding serum, but it appeared from ultracentrifugal analysis and from a lack of a consistent correlation between these assays that each assay was measuring different forms of immunecomplex-like material which may be involved in the immunopathogenesis of this disease. The C1q binding assay is of some value in the laboratory assessment of rheumatoid arthritis and appears to offer greater advantages than the monoclonal rheumatoid factor assay, although the usefulness of this latter assay may be very dependent on the monoclonal rheumatoid factor used.

Adolescent↗
PubMed1988

Analysis of rheumatoid factor autoantibodies in patients with essential mixed cryoglobulinaemia and rheumatoid arthritis.

Approximately 60% of human monoclonal rheumatoid factors from unrelated patients with cryoglobulinaemia share a common idiotype (Wa). Analysis of Ig V regions revealed that these rheumatoid factors utilize highly homologous light chains from the VKIIIb sub-subgroup. More recent studies showed a similar restriction in the use of VHI and JH4 and a restriction in the size of the D segment. In the present experiments the structural features of RFs from patients with cryoglobulinaemia were studied using a panel of murine monoclonal antibodies. The pattern of expression of these idiotypes were investigated among diverse patients with rheumatoid arthritis and normal individuals. Though in general higher levels of crossreactive idiotypes from the Wa group are detected in rheumatoid arthritis patients compared to normals, their levels in polyclonal rheumatoid factors is low. Therefore the major proportion of polyclonal rheumatoid factors in rheumatoid arthritis represent the products of somatic variants of monoclonal rheumatoid factor V genes or a larger gene pool.

Antibody Specificity↗
PubMedDate not supplied

[Stimulation of immunoglobin synthesis and rheumatoid-factor production by rheumatoid synovial effusions and by supernatants of synovial tissue cultures].

Factors capable of stimulating the synthesis of immunoglobulin by circulating human lymphocytes, as measured by a radioactive immune coprecipitation method, have been demonstrated in rheumatoid synovial eeffusions but not in effusions from patients with other arthritides. The activity of the ffusions was localized in two fractions eluted from an agarose A 5m column: fraction II eluting with IgM and fraction E eluting with albumin. Fraction II enhanced immunoglobulin synthesis only in circulating rheumatoid lymphocytes, while fraction V enhanced immunoglobulin synthesis in both rheumatoid and normal lymphocytes. Similar active fractions were found in culture supernatants of rheumatoid synovial tissue. Enhanced immunoglobulin synthesis was also observed following addition of aggregated IgG to rheumatoid lymphocytes. Finally, increased synthesis of anti-IgG (rheumatoid factor) was observed following addition of fractions II and V to rheumatoid but not to normal lymphocytes. The possible relationship of the active material in fraction II to IgG-containing immune complexes and the active material in fraction V to a T cell produced lymphokine-like mediator of T cell function are discussed. The findings presented provide evidence that in addition to antigenic stimulation, the action of one or more enhancing factors liberated by antigen stimulated mononuclear cells, possibly T lymphocytes, plays a role in the immunoglobulin synthesis observed in rheumatoid synovial tissue.

Arthritis, Rheumatoid↗
PubMed1992

Heteroclitic polyclonal and monoclonal anti-Gm(a) and anti-Gm(g) human rheumatoid factors react with epitopes induced in Gm(a-), Gm(g-) IgG by interaction with antigen or by nonspecific aggregation. A possible mechanism for the in vivo generation of rheumatoid factors.

Heteroclitic rheumatoid factors (RF) are specific for allotypic determinants, e.g., Gm(a) or Gm(g) on allogeneic, but not autologous IgG. All polyclonal RF we isolated from nine rheumatoid arthritis patients with circulating Gm(a-), (b+), (g-), (f+) IgG displayed dual heteroclitic activity for the Gm(a) and Gm(g) allotypes, as shown by using appropriate RBC agglutination assays and affinity columns bearing Gm(a+) or Gm(g+) IgG. To investigate possible mechanisms underlying the in vivo generation of heteroclitic RF, we tested the ability of nonspecifically and immune-specifically aggregated Gm(a-), (g-) IgG to function as targets for RF from Gm(a-), (g-) patients with rheumatoid arthritis. Heat aggregation (63 degrees C for 20 min) or binding to Ag (as in tetanus toxoid-antitetanus toxoid complexes) induced a "functional" Gm(a+) and/or (g+) phenotype in Gm(a-), (g-) IgG from five healthy subjects and five rheumatoid patients, as suggested by the ability of these altered IgG to function as efficient targets for six heteroclitic RF in direct binding and competitive inhibition experiments. That heterocliticity and dual Gm(a), Gm(g) specificity can be features of a single antibody molecule was formally demonstrated by analysis of a monoclonal RF (IgM mAb 61) generated from a Gm(a-), (g-) rheumatoid patient. RF mAb 61 displayed a high affinity (Kd, 10(-7) M) for IgG Fc fragment of Gm(a+) and (g+) IgG or aggregated autologous Gm(a-), (g-) IgG but did not bind to native autologous IgG. To investigate the molecular basis of the acquired Gm(a) phenotype, PBMC from five Gm(a-) patients with rheumatoid arthritis and two Gm(a-) normal subjects arthritis and two Gm(a-) normal subjects were cultured in vitro after activation with PWM. In most instances, these PBMC produced IgG that behaved as Gm(a+) in sensitive ELISA. Application of the polymerase chain reaction (PCR), using probes specific for the nucleotide sequence coding for the Gm(a) tetrapeptide, to the amplification of DNA from the in vitro-stimulated Gm(a-) normals or rheumatoid patients' PBMC provided no evidence for Gm(a) nucleotide sequences. The present data suggest that acquisition of the Gm(a) determinant by Gm(a-) IgG may result from subtle changes in the CH2-CH3 RF-binding region. Such changes would occur when Gm(a) IgG are complexed with Ag or nonspecifically altered, thereby providing a possible explanation for the induction of heteroclitic RF in Gm(a-) rheumatoid arthritis patients.

Antibodies, Monoclonal↗
PubMed2005

MRI appearance of retrocalcaneal bursitis and rheumatoid nodule in a patient with rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disorder of unknown etiology characterized by symmetric, erosive synovitis and sometimes multisystem involvement. Rheumatoid nodules have been reported in as many as 20-30% of patients with rheumatoid arthritis; however, they are not commonly seen in the feet. We present magnetic resonance (MR) findings of a rarely seen case of rheumatoid bursitis in the retrocalcaneal bursa associated with a subcutaneous rheumatoid nodule inferior to the calcaneus which histologically confirmed the rheumatoid arthritis. To the best of our knowledge, this is the first case that rheumatoid bursitis in the retrocalcaneal bursa associated with the rheumatoid nodule in the foot was revealed by MR imaging.

Adult↗
PubMed1999

Shared rheumatoid epitope as a risk factor in determining outcome in rheumatoid arthritis.

BACKGROUND: A genetic component is thought to contribute to 30-40% of the expression of rheumatoid arthritis (RA) with the HLA-DR4, w4 (B1*0401), w14 (B1*0404) genes (and associated shared rheumatoid epitope) constituting a substantial portion of this risk. AIM: Our objective was to determine the presence of these risk factors in a group of patients with RA and to correlate presence with disease outcome. METHOD: Forty-three RA patients who had been regularly assessed up to a ten year period since their initial entry into two gold treatment trials were studied. DR4, w4, w14 and shared rheumatoid epitope were determined on peripheral blood lymphocytes using flow cytometry and specific monoclonal antibodies. Disease outcome was measured by Health Assessment Questionnaire (HAQ) score and C-Reactive Protein (CRP) as a serological measure of joint inflammation. RESULTS: To confirm accuracy of the flow cytometric technique, DR typing and epitope status was compared with results obtained by genotyping in a subset of 14 patients. There was complete concordance between these two techniques for the rheumatoid epitope. However, concordance was not complete (both false positives and false negatives) for DR4, w4 and w14. Hence the presence of rheumatoid epitope was only evaluated further in the larger group. The presence of the shared rheumatoid epitope correlated positively with poorer outcome on serological assessment (p < 0.05). No significant correlation between HAQ score and rheumatoid epitope status was observed although a weak trend was noted. CONCLUSION: These studies suggest that determination of rheumatoid epitope status by flow cytometry may provide useful data concerning the long term outcome of patients with RA.

Aged↗
PubMed2004

Raised granzyme B levels are associated with erosions in patients with early rheumatoid factor positive rheumatoid arthritis.

BACKGROUND: Raised granzyme B in serum and synovium of patients with rheumatoid arthritis suggests a role for cytotoxic T cells and natural killer cells in the pathogenesis of this disease. OBJECTIVE: To evaluate serum granzyme B in patients with early arthritis and correlate it with specific diagnosis and clinical indices of disease severity. METHODS: 257 patients with inflammatory arthritis for less than one year (46% rheumatoid arthritis, 17% spondyloarthropathy, 37% undifferentiated arthritis) had a prospective clinical, serological, and radiographic evaluation. Granzyme B was measured in initial sera by ELISA. Patients were HLA typed for DR alleles using sequence specific primers. A logistic regression model was used to evaluate the potential prognostic value of serum granzyme B in predicting radiographic erosions after one year of follow up. RESULTS: Granzyme B values were similar in rheumatoid arthritis, spondyloarthropathy, and undifferentiated arthritis. Concentrations were higher in rheumatoid factor (RF) positive patients than in RF negative patients (mean (SD): 3.15 (0.92) v 2.89 (0.71) pg/ml; p<0.05). After one year, erosions were present in 30% of patients in the overall cohort, and in 44% of patients with rheumatoid arthritis. In the entire cohort, serum granzyme B did not predict erosions independently. However, high granzyme B was an independent predictor of early erosions in patients with RF positive rheumatoid arthritis (odds ratio = 4.83 (95% confidence interval, 1.13 to 20.59)) (p<0.05). CONCLUSIONS: Granzyme B may be a useful prognostic marker in early rheumatoid arthritis and may provide important clues to the pathogenesis of this disease.

Adult↗
PubMed1980

Lack of hidden complement fixing IgM rheumatoid factor in adult seronegative rheumatoid arthritis.

IgM rheumatoid factors capable of complement fixation and activation are commonly present in the sera of adults with rheumatoid arthritis. Hidden complement fixing IgM rheumatoid factor has been demonstrated in the majority of patients with juvenile RA and hidden agglutinating IgM rheumatoid factors have been demonstrated in the serum of adults with seronegative rheumatoid arthritis. We studied 27 adults with seronegative rheumatoid arthritis and were unable to demonstrate hidden complement fixing IgM rheumatoid factor in their sera.

Adult↗
PubMed1988

Complement mediated inhibition of immune precipitation in rheumatoid arthritis: studies on interaction of heat aggregated IgG with IgM rheumatoid factor.

Serum samples from patients with seropositive rheumatoid arthritis contain an inhibitor of complement mediated inhibition of immune precipitation (CMIP). This inhibitory effect can be produced by the addition of either purified monoclonal or polyclonal IgM rheumatoid factor (RF) to human serum. The specificity of the rheumatoid factor influences the degree of inhibition, and when precipitation occurs the rheumatoid factor coprecipitates with the antigen-antibody complex. In rheumatoid sera there was a significant positive correlation between IgM RF concentration and inhibitory activity, though the range of inhibitory activity seen for the same concentration of rheumatoid factor was considerable. Small quantities of heat aggregated IgG (HAGG) had a much greater effect on the measurement in an enzyme linked immunosorbent assay (ELISA) of IgM RF than they did on the inhibitory activity of IgM RF in the CMIP assay. Larger quantities of HAGG initiated complement activation and increased the precipitation of immune complexes. IgM RF reduced the complement activating properties of HAGG by reducing the amount of Clq which bound to the aggregate. The mechanisms by which IgM RF overcomes CMIP in rheumatoid sera may involve its inhibitory effects on the binding of Cl to the antigen-antibody complex.

Antigen-Antibody Complex↗
PubMed1970

Low incidence of rheumatoid factor and autoantibodies in Nigerian patients with rheumatoid arthritis.

Sera from 53 Nigerian patients satisfying the American Rheumatism Association criteria for a diagnosis of definite or probable rheumatoid arthritis and sera from sick and healthy Nigerian controls were tested for rheumatoid factor, autoantibodies, and immunoglobulin levels. Rheumatoid factor and autoantibodies were found no more frequently in patients with rheumatoid arthritis than in controls. These findings confirm the clinical impression that Nigerian patients with polyarthritis satisfying the criteria for a diagnosis of rheumatoid arthritis differ from Caucasian patients with the disease in a number of important respects. They suggest that either these patients do not have rheumatoid arthritis but a distinct clinical syndrome or that in Nigeria the course of rheumatoid arthritis is modified by genetic or environmental factors.

Adolescent↗