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PubMed2005

Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population.

Melatonin is reported to be an anti-inflammatory agent. No genetic study concerning the association between melatonin and inflammatory disease has yet been reported. Here we performed a polymorphism study on the melatonin receptor type 1B (MTNR1B) in Korean rheumatoid arthritis (RA) patients and controls. The polymorphism of MTNR1B located in 3'-untranslated region (rs 1562444) was selected for its higher rate of heterozygosity among other single nucleotide polymorphisms (SNPs) in both MTNR1A and MTNR1B genes and investigated in RA patients (n = 173) and healthy controls (n = 195) by polymerase chain reaction-restriction fragment length polymorphism assay using NlaIII restriction enzyme. No statistically significant difference in either genotype distribution or allele frequency was observed between RA patients and controls. The genotype distributions and allele frequencies of rheumatoid factor negative [RF(-)] patients were similar to those of controls. However, statistical analysis of genotype revealed a significant association (chi2 = 6.42, P = 0.04) is present between RF(+) and MTNR1B SNP (rs 1562444). Although no statistically significant difference in allele frequency between RF(+) and controls was observed (chi2 = 2.75, P = 0.10), the results might suggest that MTNR1B SNP (rs 1562444) is associated with the presence of RF in RA. This is the first study, to our knowledge, to report a positive genetic relationship between melatonin and RA.

Arthritis, Rheumatoid↗
PubMed1986

Effects of gold therapy on the synthesis and quantity of serum and synovial fluid IgM, IgG, and IgA rheumatoid factors in rheumatoid arthritis patients.

Eleven patients with active rheumatoid arthritis were monitored prospectively while receiving up to 1 gm of gold sodium thiomalate. There was a significant decrease in serum and synovial fluid IgG, IgA, and IgM rheumatoid factor (RF) levels over the period of study. Comparison of changes in serum RF and total immunoglobulin levels indicated a selective effect on RF production. These observations were supported by changes in the spontaneous in vitro production of IgM-RF and total IgM by peripheral blood mononuclear cells. Studies of synovial membrane synthesis showed a downward trend in immunoglobulin and RF production, but this did not reach statistical significance. A differential effect on the various RF classes was also noted. The most profound effect was on IgM-RF production; whereas, changes in IgG-RF production were least affected. These results suggest a selective and differential effect of gold salts on RF production.

Adult↗
PubMed1979

Performance of latex-fixation kits used for serologic diagnosis of rheumatoid factor in rheumatoid arthritis sera.

Ten latex-fixation kits (both slide and tube) were evaluated by use of a reference serum containing 250 IU of rheumatoid factor (Communicable Disease Center). All tests were performed with serial dilution of serum; adjacent tubes differed by a factor of 0.10 log10. Geometric titers, means, standard deviations, and variance analysis were used to evaluate commercial kits. Three levels of variance were applied: (1) 0.18 or less for intralaboratory variation when the same serum is tested with the same kit; (2) 0.18-0.35 when various lots or batches of the same serum were used; (3) 1.0 or less when various commercial kits were tested with the same serum. The sensitivity of each commercial kit was determined by assigning to it a value (the minimum detectable unit) arrived at by dividing the number of units in the standard by the titer obtained. The technic presented could be applicable to other serologic tests, and thus provide a general method for their standardization and quality control.

Arthritis, Rheumatoid↗
PubMed1990

IgG and IgA subclass distribution of total immunoglobulin and rheumatoid factors in rheumatoid tissue plasma cells.

The subclass distribution of IgG and IgA plasma cells, and in IgG and IgA rheumatoid factor (RF) producing cells was studied in sections of synovial tissue from seropositive RA and various types of seronegative arthritis, including ankylosing spondylitis, psoriatic arthritis, and Reiter's syndrome. The study was performed with immunofluorescence technique and monoclonal IgG and IgA subclass specific antibodies. IgG RF producing cells were identified by their ability to bind and activate factors both in the early (C3) and late (C5b-9) part of the complement cascade. IgA RF cells were identified by double staining experiments with heat-aggregated IgG and monoclonal antibodies to IgA subclasses. In 23 tissues tested for total IgG, IgG1 cells were usually predominant, while the frequency of IgG3 cells was usually higher than that of IgG2. In 19 tissues also tested for IgA, both IgA subclasses were present in all tissues. IgA1 plasma cells were always predominant, with a mean ratio of IgA1 to IgA2 cells of approximately 10. In the 13 tissues tested for RF-producing cells, the highest frequency of IgG RF cells was found among the IgG3 cells, followed by IgG1 and IgG2. IgA RF cells were found in only one case, all cells being IgA1.

Antigen-Antibody Complex↗
PubMed1980

Enhanced in vitro synthesis of IgM rheumatoid factor in rheumatoid arthritis.

Peripheral blood mononuclear leukocytes (MNL) from 42 patients with classic/definite seropositive rheumatoid arthritis (RA) and 24 healthy adult controls were tested for their capacity to produce IgM rheumatoid factor (RF) in vitro in the presence and absence of pokeweed mitogen (PWM). In no instance was spontaneous elaboration of IgM RF from control MNL observed. In contrast, MNL from 16 of the 42 RA patients spontaneously synthesized IgM RF (22 +/- 43 ng/culture) which constituted a substantial fraction of the total IgM in these culture fluids (48 +/- 26%). Pokeweed mitogen induced detectable quantities of IgM RF in MNL culture supernatants from 10 of 24 controls (12 +/- 11 ng/culture) and 33 of 42 RA patients (60 +/- 82 ng/culture, P = 0.008). IgM RF constituted a significantly higher proportion of the total IgM in RA MNL supernatants than in control supernatants (11 +/- 11% versus 1.01 +/- 1.03%; P = 0.013). IgM RF production (spontaneous and PWM-induced) was dependent upon de novo protein synthesis. The results indicate that B cells programmed to produce IgM RF are present in both normal and RA B cell repertoires, but are preferentially expressed in RA.

Animals↗
PubMed1995

[IgG rheumatoid factor in rheumatoid arthritis with interstitial lung disease].

Case of rheumatoid arthritis (RA) with interstitial lung disease (ILD) have been reported to show increased titers of rheumatoid factor (RF) in serum; however the pathogenic role of this substance in the lung is still obscure. The aims of this study were to estimate IgGRF in the bronchoalveolar lavage fluid (BALF) in RA and to investigate its possible roles in the ILD of RA. Two step bronchoalveolar lavage in 20 RA patients (9 males, 11 females) was performed in conjunction with high resolution chest CT. IgGRF was measured by enzyme-linked immunosorbent assay and its molecular size in BALF was evaluated by high performance liquid chromatography. IgGRF bound to BALF cells was eluted by sonication of the cells. RA patients with ILD had significantly elevated levels of IgGRF in serum as well as in BALF. The IgGRF in BALF was monomeric in 2 of 3 RA patients with ILD. The activity of IgGRF bound to BALF cells was significantly higher in RA with ILD than in control patients. These findings suggest that monomeric IgGRF in the lungs of RA patients could bind to the cells with Fc receptors.

Aged↗
PubMed1983

IgG and IgM rheumatoid factors in rheumatoid arthritis. Quantitative response to penicillamine therapy and relationship to disease activity.

Penicillamine treatment of patients with rheumatoid arthritis (RA) leads to falling titers of agglutinating IgM rheumatoid factor (RF), but its effect on IgG RF has not been described. Using specific solid phase radioimmunoassays, we have determined serial levels of IgM RF and IgG RF in 18 patients receiving penicillamine for 1 year, and correlated the results with the change in RA activity. Mean IgM RF levels fell to 76 +/- 10% (mean +/- SEM) after 3 months, and 30 +/- 5% of the pretreatment value after 1 year of penicillamine treatment. This decline was greater than that for total IgM (P less than 0.0001), indicating a selective reduction of RF. Patients receiving maintenance doses of 750 mg/day manifested more rapid and greater decreases than did those given 250 mg/day. In contrast, serial mean IgG RF levels did not change significantly, and actually increased in 6 of 18 cases. At onset, there was a significant correlation with erythrocyte sedimentation rate for both IgM RF (r = 0.535, P = 0.05) and IgG RF levels (r = 0.570, P = 0.02). But changes in RF concentration demonstrated no correlation with changes in either erythrocyte sedimentation rate or joint score over the 1-year period, suggesting that circulating IgM RF or IgG RF levels may be unrelated to the degree of RA activity.

Adult↗
PubMedDate not supplied

IgA isotype rheumatoid factor in rheumatoid arthritis: clinical implications.

OBJECTIVES: To study the clinical, biological and radiological characteristics of RA with a predominant increase of IgA isotype rheumatoid factor (IgA-RF) over IgM-RF. METHODS: The presence of IgA-RF was determined by a sandwich-type ELISA with an antibody against the human IgA used to capture the immunoglobulin. Associated RF activity was revealed with a peroxidase-conjugated human IgG Fc fragment. Forty-nine RA patients were studied, of whom 19 had an increase in IgA-RF (38%). The control group comprised 30 RA patients without IgA-RF. RESULTS: None of the patients had isolated IgA-RF. In the selected 19 RA patients, the OD of IgA-RF (0.971 +/- 0.62 U) was higher than the IgM-RF (mean OD: 0.675 +/- 0.522 U). A statistically significant correlation was found between IgA-RF and IgM-RF (r = 0.64, p < 0.0001). No correlation was noted between the IgA concentration and the IgA-RF titer. The two groups were comparable for age, disease duration, sex ratio and previous DMARD use. We observed that patients with RA associated with increased IgA-RF more often had the sicca syndrome, but no other extra-articular features. RA patients with IgA RF also had more erosive disease: the mean Larsen score at the hand and wrist was 76 (SD = 68) versus 54 (SD = 60) in the controls, p < 0.02. Replacement surgery for the hip or knee was necessary in 47% of the RA patients with IgA-RF, versus 13% in the controls, p < 0.01. No association of IgA-RF with disease activity was noted. CONCLUSION: Our study showed that RA patients with a predominant increase of IgA-RF had a more erosive disease and a high frequency of associated sicca syndrome.

Arthritis, Rheumatoid↗
PubMed1991

[Rheumatoid factor in rheumatoid arthritis in old age].

Rheumatoid factors (RF) detected by agglutination methods (latex fixation test, haemagglutination test) were found in a group of patients with rheumatoid arthritis which started in advanced age (RAVV) less frequently than in a group with RA in middle age (RAMV). The author describes the ELISA method for assessment of RF which makes it possible to estimate immunoglobulin classes RF (IgM-RF, IgA-RF, IgG-RF). By this method RF were detected in class IgM in 15% of patients and in some immunoglobulin classes in 20 per cent where are RF negative when assessed by agglutination methods. The ELISA method detects probably also so-called "hidden" RF. In the group of healthy subjects above 60 years at least one class of RF rises to 17.5%. On correlation with the clinical status an association was found with the degree of affection according to the functional score, with the presence of rheumatoid nodes and muscular affection in RA. Patients with RA treated with Methotrexate and Sulfasalazine tend to have declining IgG RF levels.

Age Factors↗
PubMed1995

[The association of the disease activity of rheumatoid factor positive vasculitis and the level of rheumatoid factor].

Rheumatoid factor (RF), an autoantibody against the Fc portion of denatured IgG, has long been recognized as an important biologic marker not only for rheumatoid arthritis but also for other auto-immune diseases. In this study, we measured the level of serum RF in four patients with RF positive systemic vasculitis using laser nephelometry. Three patients were diagnosed as polyarteritis nodosa and the other patient was diagnosed as systemic vasculitis without the finding of typical necrotizing vasculitis from biopsies. In the result, we found that the level of RF paralleled the disease activity in these cases. When active phase of the disease, the level of RF showed very high, and after the treatment combined with plasmapheresis, corticosteroid and immunosuppressive agent, the level of RF decreased in accordance with CRP, ESR and clinical features. These suggested that RF was the disease specific marker for RF positive vasculitis and beneficial informations for proper diagnosis and better treatment could be provided by measurement of the level of RF in patients with RF positive systemic vasculitis.

Adult↗
PubMed1991

The major rheumatoid factor crossreactive idiotype and IgA rheumatoid factor in juvenile rheumatoid arthritis.

One third of patients with juvenile rheumatoid arthritis (JRA) are seronegative for classic or hidden IgM rheumatoid factor (RF) yet express the major RF crossreactive idiotype (RCRI). We studied 60 children with JRA and 57 pediatric controls for IgA RF and RCRI expression to determine whether RCRI is associated with IgA RF in JRA. Twenty-one patients had IgA RF using rabbit or human IgG as substrate. Twenty-seven patients with JRA expressed high concentrations of RCRI in their sera. Only 9 of these had IgA RF. Eleven of the RCRI+ sera contained neither IgA RF nor classic or hidden IgM RF, and IgA RF was found in patients with all JRA onset subtypes. In JRA, RCRI may be expressed on either IgG RF or on parallel set antibodies without RF activity.

Adolescent↗
PubMedDate not supplied

Immunoglobulin E-rheumatoid factor in juvenile rheumatoid arthritis.

OBJECTIVES: To determine the presence of immunoglobulin E-rheumatoid factor in patients with juvenile rheumatoid arthritis and to correlate it with clinical and laboratory parameters. METHODS: A multicenter prospective study was carried out from January 1993 to January 1999 with the enrollment of 3 centers of pediatric rheumatology. Ninety-one children with juvenile rheumatoid arthritis diagnosed according to the American College of Rheumatology criteria were studied: 38 (42%) with systemic, 28 (31%) with pauciarticular, and 25 (27%) with polyarticular onset. Ages ranged from 2.1 years to 22.6 years (mean 10.5 +/- 4.7), with 59 (65%) girls. The control group consisted of 45 healthy children. The detection of immunoglobulin E-rheumatoid factor was carried out utilizing an enzyme-linked immunosorbent assay. Associations of immunoglobulin E-rheumatoid factor with immunoglobulin M-rheumatoid factor (latex agglutination test), total serum immunoglobulin E, erythrocyte sedimentation rate, antinuclear antibody, and functional and radiological classes III or IV were analyzed. RESULTS: Positive immunoglobulin E-rheumatoid factor was found in 15 (16.5%) of the 91 children with juvenile rheumatoid arthritis: 7 (18.5%) with systemic, 5 (18%) with pauciarticular, and 3 (12%) with polyarticular onset. A significant correlation was observed between immunoglobulin E-rheumatoid factor and total serum immunoglobulin E in the juvenile rheumatoid arthritis patients. No correlation was found between immunoglobulin E-rheumatoid factor and positive latex agglutination slide test, erythrocyte sedimentation rate, antinuclear antibody, or the functional and radiological classes III or IV in any disease onset group. In 4 out of 45 control children (8.9%), immunoglobulin E-rheumatoid factor was positive but with no correlation with total serum immunoglobulin E levels. CONCLUSIONS: Immunoglobulin E-rheumatoid factor could be detected in 16.5% of juvenile rheumatoid arthritis patients, particularly in those with high levels of total serum immunoglobulin E, and immunoglobulin E-rheumatoid factor appears not to be associated with disease activity or severity.

Adolescent↗
PubMed1996

Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis.

OBJECTIVE: To determine the diagnostic and prognostic test qualities of the enzyme linked immunosorbent assays (ELISA) for rheumatoid factor isotypes in rheumatoid arthritis (RA), and to compare them with the latex fixation test. METHODS: Rheumatoid factor tests were performed in 1988 consecutive new rheumatology outpatients within two months after their first visit to the outpatient clinic of the Department of Rheumatology of Leiden University hospital. The sensitivity, specificity, accuracy, and predictive values of the tests in discriminating RA from non-rheumatoid arthritis and erosive from non-erosive disease after two years of follow up were determined and presented as receiver operating characteristic curves and post-test probability curves. RESULTS: The sensitivity of the ELISA for IgG, IgA, and IgM rheumatoid factor for RA versus all controls at optimal cut off titres was 72%, 44%, and 69%, respectively; the specificity was 52%, 84%, and 86%. For the latex fixation test the sensitivity was 66% and the specificity 91%. The post-test probability of RA, at a clinical prevalence rate of 12%, given a positive test result in the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, was 17%, 27%, 40%, and 49%, respectively; with negative test results the probability was 7%, 8%, 5%, and 5%, respectively. The specificity of all tests in discriminating erosive from non-erosive RA at two years was low: 41%, 44%, 47%, and 58% for the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, respectively. CONCLUSION: The ELISAs for IgG and IgA rheumatoid factor are of no significance in diagnosing RA and in the prediction of erosive disease. The ELISA for IgM rheumatoid factor is a reasonable alternative for the latex fixation test when age and gender are taken in to consideration. The specificity of all rheumatoid factor tests in discriminating erosive from non-erosive RA is low.

Adolescent↗
PubMed1987

Antigen-induced rheumatoid factors. Protein and carbohydrate antigens induce different rheumatoid factor responses.

Rheumatoid factors, autologous IgM anti-IgG, were produced after immunization with protein or carbohydrate antigens. After immunization with either type of antigen, the kinetics of the rheumatoid factor response reflected the kinetics of the dominant IgG isotype in the anti-antigen response. Secondary immunization with protein antigens induced an IgM rheumatoid factor response which was consistently greater than that seen after carbohydrate immunization, and almost exclusively specific for the IgG1 isotype. In contrast, primary or hyperimmunization with carbohydrate antigens gave rise to a more heterogeneous response dominated by IgM anti-IgG3, with lesser amounts of IgM anti-IgG2b and anti-IgG1. Direct immunization with immune complexes gave similar results, as complexes composed of IgG1 induced exclusively IgM anti-IgG1, whereas those complexes made up of IgG3 gave rise to IgM rheumatoid factors binding IgG3 and IgG2b. Rheumatoid factor production, with isotypic specificity defined by the immunizing antigen, appears to be a natural consequence of immunization with a variety of protein and carbohydrate antigens.

Animals↗
PubMed1980

The isolation of immune complexes containing IgM rheumatoid factor and recovery of IgG rheumatoid factor from the complexes.

IgG with rheumatoid factor activity has been recovered from immune complexes containing IgM rheumatoid factor. This was done by passing serum from patients with rheumatoid arthritis through an immunoadsorbent column of the F(ab')2 fragment of rabbit anti-human mu chain. The recovered IgM was analysed by radioimmunoassays for IgM and IgG rheumatoid factors before and after sucrose density gradient centrifugation at neutral and acid pH. It is considered that the method may be generally applicable for the isolation of immune complexes containing IgM antibodies.

Animals↗