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PubMed1982

Human complement activation by self-associated IgG rheumatoid factors.

IgG rheumatoid factors (IgG-RFs) undergo concentration-dependent self-association into dimers and higher polymers, as previously reported. The interactions of purified IgG-RF from the plasma of 3 patients with rheumatoid arthritis, with guinea pig and human complement were studied. Self-associating IgG-RFs were isolated by affinity columns and gel filtration. These preparations contained no detectable IgM and were composed only of IgG subclasses known to fix complement. Complement utilization of IgG-RF was compared with that of monomeric IgG, heat-aggregated IgG, and soluble rabbit IgG immune complexes. Although incubation of IgG-RF or monomeric IgG with 3 units of guinea pig or human complement resulted in decreased hemolysis of sheep erythrocytes sensitized with IgM hemolysin, these substances were less than 100 times as effective as heat-aggregated IgG or soluble immune complexes. The ability of human or guinea pig complement that had been incubated with IgG-RF to restore hemolytic activity to C4-deficient guinea pig serum served to distinguish Clq binding from complement cascade activation. IgG-RFs and monomeric IgG did not activate guinea pig complement cascade in contrast to aggregated IgG. IgG-RFs, however, activated human complement cascade; monomeric IgG only bound human Clq. These results indicate that self-associated IgG-RFs can activate human complement in fluid phase, but less effectively than aggregated IgG or large-latticed immune complexes.

Arthritis, Rheumatoid↗
PubMed1977

Rheumatoid factor in non-rheumatoid black patients.

A total of 301 Black patients without rheumatic diseases was studied to estimate the prevalence and causes of positive rheumatoid factor. The latex slide test was positive in 25% of patients and 21% had a 'diagnostic' titre of 80 or more. A significant relationship between gamma-globulin levels and rheumatoid factor positivity was demonstrated. IgG appeared to be the most important in determining this relationship. The most common ailments among sero-positive patients were cirrhosis and tuberculosis.

Adolescent↗
PubMedDate not supplied

Regulation of rheumatoid factor synthesis.

Rheumatoid arthritis is associated with high titers of IgM and IgG autoantibodies against IgG (rheumatoid factors, RF) and is prevalent in individuals with the HLA haplotypes Dw4, Dw14 and DR1. Our investigations have aimed to determine the molecular genetic basis for RF autoantibody synthesis in people, in an effort to understand eventually how RF production may become improperly regulated in rheumatoid patients. The results have defined several cross-reactive idiotypes on the heavy and light chains of RFs that are serologic markers for specific immunoglobulin variable region genes. These autoantibody associated genes are highly conserved in human populations and are preferentially rearranged and expressed during early B cell development, and in certain lymphoproliferative diseases. They may be associated with a B cell subpopulation that is important for the processing and presentation to T cells of protein antigens trapped in immune complexes. These RF-associated idiotypes are eventually lost during the T cell dependent antibody diversification that accompanies rheumatoid arthritis. The stimuli for the diversification have not been clearly established. However, the rheumatoid arthritis disease susceptibility determinant on the beta-1 chain of individuals with the HLA Dw4, Dw14 or DR1 haplotypes is reproduced by the gp110 protein of the Epstein-Barr virus, and is a potent stimulus for T cell proliferation. Moreover, anti-gp110 antibodies are abundant in rheumatoid arthritis patients. Thus, it is possible that their continual binding and processing of gp110-IgG immune complexes by RF precursor B cells in the joints and other extravascular sites may lead to the emergence of self-reactive T cells that can trigger anti-IgG autoantibody synthesis in the absence of an external antigen.

Arthritis, Rheumatoid↗
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↗
PubMed1980

A latex test for canine rheumatoid factor.

Canine rheumatoid factor (RF) has been reported in several canine diseases, particularly in arthritis. Although RF can be assayed using IgG sensitized erythrocytes, the test has a number of disadvantages. As an alternative, latex sensitized with canine IgG was investigated as an assay of canine RF. The canine IgG-latex could be easily produced, was stable, and could be standardized with commercial antisera. The reagent detected RF of the IgM anti-canine-aggregated-IgG type. A comparison of the titres obtained using the canine IgG-latex reagent with those obtained using a rabbit IgG-erythrocyte reagent showed no correlation, suggesting that the two assays may detect RF of different specificities.

Animals↗
PubMed1976

The frequency of 7S rheumatoid factors and 22S complexes in human sera with positive latex tests for rheumatoid factor.

In sera with positive latex tests for rheumatoid factors, the immunoglobulin class of the antiglobulins is influenced by the quantity of immunoglobulins present in the serum. Sera with 7S antiglobulins have high levels of IgG and IgA immunoglobulins. 22S complexes tend to be found in sera with high levels of IgM immunoglobulins. These findings suggest that the occurrence of antiglobulins and 22S complexes may be influenced by the hypergammaglobulinemia.

Adsorption↗
PubMed1981

Nephelometry v differential agglutination titre in the measurement of rheumatoid factors.

IgM rheumatoid factors have been measured in 92 patients by both laser nephelometry and the traditional hospital procedure of a latex slide test followed by differential agglutination titre (DAT). Of the results 86% were in accordance by both methods, but seronegative patients with a high nephelometry score all showed, after reference to their clinical state and previous investigations, that the nephelometry result more accurately represented their clinical state than the DAT, which was shown to be in error in five out of the six cases. Six seropositive patients with low nephelometry scores were also studied; three were in complete remission on gold or penicillamine therapy. Nephelometry is both technically simpler and more reliable than the traditional DAT method, and our results suggest that it has some advantages over the DAT in routine use.

Agglutination Tests↗
PubMed1988

The epitope specificity and idiotypy of monoclonal rheumatoid factors.

Monoclonal rheumatoid factors (MRF) of the Wa idiotypic family have been studied for Fc gamma epitope specificity and the expression of idiotopes recognized by murine monoclonal antibodies. The majority of MRF recognized the Ga antigen or a closely similar iso-allotypic epitope expressed on IgG1, 2, 4 and IgG3.G3m(s.t.) proteins. MRF having the iso-allotypic specificity expressed a similar profile of V-region sub-group and idiotypic serological markers. One protein, Kas, whilst recognizing a distinct Fc gamma epitope also expressed these V-region markers and was highly homologous, from primary sequence analysis, with a MRF of Ga specificity. We conclude that these MRF recognize overlapping non-identical epitopes possibly including the same immuno-dominant residue and consequently demonstrate restricted V-gene usage.

Antibodies, Monoclonal↗
PubMed1989

[Sero-epidemiological study of the variability of rheumatoid factors].

Serum rheumatoid factors (RF) are occasionally observed in normal individuals. The clinical significance of the appearance of RF in the general population was examined in relation to the pattern of their appearance and the age of the onset of RA. A screening for RA in the residents of Yoshimatsu-Cho, Kagoshima Prefecture (population, 4,798), showed a prevalence of 0.29%, but the sera of 128 (4.0%; 3.4% for males and 4.5% for females) of 3,200 residents obtained at the screening were positive for RF, and the percent positivity tended to increase with age. The age of the onset of RA in 466 patients exhibited a nearly normal distribution with a peak in the 40's. From these findings, RF-positive individuals in the general population may be divided into a small group predisposed to RA and a great majority in whom the positivity is simply an age associated physiologic change.

Adolescent↗
PubMed1985

Suppression of rheumatoid factor synthesis by antiidiotypic antibody in rheumatoid arthritis patients with cross-reactive idiotypes.

The effect of antiidiotypic antibody on the in vitro production of rheumatoid factor was studied in rheumatoid arthritis patients with cross-reactive idiotypic determinants. Antiidiotypic antibodies (ascites IgG) were developed against monoclonal rheumatoid factor (Ka m-RF) by a cell fusion procedure. These antibodies were idiotype-specific, since: 1) they reacted only with F(ab')2 fragment of Ka m-RF; 2) they failed to react with normal IgM without rheumatoid factor activity; and 3) their F(ab')2 fragment inhibited the rheumatoid factor activity of Ka m-RF. The antiidiotypic antibody strongly suppressed the in vitro production of rheumatoid factor by lymphocytes from unrelated rheumatoid arthritis patients with cross-reactive idiotypes. The suppression was specific, since ascites IgG failed to suppress in vitro anti-keyhole limpet hemocyanin antibody production by the lymphocytes. These results indicate that antiidiotypic antibody may influence the regulation of rheumatoid factor production in patients with rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1980

Metabolism of C4 and factor B in rheumatoid arthritis. Relation to rheumatoid factor.

Metabolic turnover determined by radioiodide labeled C4 and Factor B was studied in 18 patients with rheumatoid arthritis (RA) and 19 normal control subjects as a means of estimating the relative ratio of consumption of components in the classical and alternative pathways of complement activation. Predominance of fractional catabolic rate (FCR) of C4 over Factor B was demonstrated with differentially labeled C4 and Factor B. The hypercatabolism occurred in the extravascular space. C4 FCR correlated significantly with rheumatoid factor (RF) determined in a hemolytic assay (rs = 0.72), measured as IgG RF (rs = 0.57), and as IgM RF (rs = 0.45). There were no significant correlations with several other antibodies measured. These results are consistent with the hypothesis that RA is a systemic, extravascular immune complex disease, in which RF immune complexes play a significant pathogenetic role principally via activation of the classical pathway of complement.

Adult↗
PubMed2005

The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the changes in anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) following etanercept treatment in patients with rheumatoid arthritis. METHODS: The study included 90 patients with rheumatoid arthritis who failed treatment with disease modifying antirheumatic drugs (DMARDs). All patients were allowed to continue treatment with DMARDs; 52 of them received etanercept as a twice weekly 25 mg subcutaneous injection for three months, and the others did not. Serum samples were collected at baseline and one month intervals during the treatment course. The serum levels of anti-CCP and RF were tested by enzyme linked immunosorbent assay and nephelometry, respectively. RESULTS: At baseline, 45 of the 52 etanercept treated patients (86.5%) and 32 of the 38 controls (84.2%) were positive for anti-CCP. Tests for RF were positive in 78.9% and 84.2% of patients with or without etanercept treatment, respectively. The serum levels of anti-CCP and RF decreased significantly after a three month etanercept treatment (p = 0.007 and p = 0.006, respectively). The average decrease from baseline calculated for each individual patient in the etanercept treated group was 31.3% for anti-CCP and 36% for RF. The variation in anti-CCP was positively correlated with the variation in disease activity, swollen and tender joint counts, RF, and C reactive protein. CONCLUSIONS: Etanercept combined with DMARDs leads to a much greater decrease than DMARDs alone in the serum levels of anti-CCP and RF in rheumatoid arthritis, compatible with a reduction in clinical disease activity.

Acute-Phase Proteins↗
PubMed1987

Natural killer (NK) cells at inflammatory sites of patients with rheumatoid arthritis and IgM rheumatoid factor positive polyarticular juvenile rheumatoid arthritis.

NK cell activity and Leu 7+ cells were determined in mononuclear cells (MNC) from patients with rheumatoid arthritis (RA) and IgM rheumatoid factor positive polyarticular juvenile rheumatoid arthritis (JRA). NK cell activity was measured in a 51Cr release assay and the Leu 7 positive cells were enumerated in indirect immunofluorescence. The mean NK cell activity +/- SEM was reduced in MNC from peripheral blood (PB), synovial fluid (SF) and synovial membranes (SM's) of patients with RA, with the values of 19.5 +/- 1.4 (p less than 0.00003), 18.3 +/- 3.1 (p less than 0.009) and 2.9 +/- 0.5 (p less than 0.0003) respectively, compared with 26.1 +/- 1.4 in MNC from the PB of healthy controls. The mean percentages of Leu 7 positive cells in MNC from PB and SF on patients with RA were normal while the mean percentage of Leu 7+ cells in MNC eluted from SM's was significantly reduced as compared to that of MNC from PB of healthy controls (p less than 0.0006). In JRA similar results concerning NK activity and Leu 7 positive cells were found but the number of experiments was too low for statistical analysis. MNC from the SF, in contrast to that of BP and SM, had a significant cytotoxicity against the Raji cell line which is a non-NK cell target.

Adolescent↗
PubMed1986

Utility of rheumatoid factor in the diagnosis of juvenile rheumatoid arthritis.

Rheumatoid factor is commonly used by clinicians to assess children with possible juvenile rheumatoid arthritis. To assess its usefulness, we reviewed the case histories of patients in whom latex agglutinating rheumatoid factor was determined during 1981 to 1982 at our institution. A total of 437 charts were available for review. There were 11 patients with positive tests for rheumatoid factor, of whom five had juvenile rheumatoid arthritis, all polyarticular. A total of 426 children had negative results, of whom 100 had juvenile rheumatoid arthritis. This yields a sensitivity of 4.8% and a specificity of 98%. We then estimated the prevalence of juvenile rheumatoid arthritis in three clinical settings: a primary practitioner's office, a tertiary children's hospital walk-in clinic, and a pediatric rheumatology center. The predictive values and marginal benefits for rheumatoid factor were then calculated in those settings using Bayes' theorem. In the two general outpatient settings, the primary practitioner's office and tertiary walk-in clinic, the positive predictive values were 0.7% and 0.5%, respectively; marginal benefits were 0.4% and 0.3%, respectively. Rheumatoid factor testing appeared to be of some benefit in the pediatric rheumatology center with a positive predictive value of 72.5% and marginal benefit of 22.5%. In no case was rheumatoid factor testing helpful in establishing a diagnosis of juvenile rheumatoid arthritis or in ruling it out. Testing for rheumatoid factor is a poor screening procedure for juvenile rheumatoid arthritis in the general situations in which it is more likely to be requested and of supportive diagnostic value only in the highly restricted population of older children with polyarticular arthritis.

Arthritis, Juvenile↗
PubMed1993

Rheumatoid factors from patients with rheumatoid arthritis react with tryptophan 60 and 95, lysine 58, and arginine 97, on human beta 2-microglobulin.

OBJECTIVE: To define precise epitopes on human beta 2-microglobulin (beta 2m) reacting with polyclonal IgM rheumatoid factors (RF) from patients with rheumatoid arthritis (RA). METHODS: Ten polyclonal RF were tested for their human beta 2m epitope-binding specificities using the entire 99-amino acid sequence synthesized as overlapping 7-mers in an enzyme-linked immunosorbent assay. Glycine substitution for each residue within RF-reacting linear regions was employed to define major reactive sites. RESULTS AND CONCLUSION: Major beta 2m residues contributing to RF reactivity were tryptophans at positions 60 and 95, lysine at 58, and arginine at position 97.

Amino Acid Sequence↗
PubMed1988

Partial amino acid sequence analysis and variable subgroup determination (VH and VL) of a monoclonal rheumatoid factor derived from a rheumatoid arthritis patient.

Continuous cell lines secreting monoclonal rheumatoid factors (RF) were derived from rheumatoid arthritis (RA) patients by cloning Epstein-Barr virus (EBV) transformed B cells and by hybridoma techniques. We studied five different clones with stable RF secretion. All were IgM, 4 kappa and 1 lambda. One of these clones, RFAN was extensively studied, and the partial amino acid sequences of the variable regions of both heavy and light chains were determined. After affinity purification, the IgM lambda RF antibody derived from the EBV clone was run under reducing conditions on SDS-polyacrylamide gel electrophoresis. The separated heavy and light chains were blotted and then sequenced by a gas-phase sequenator. The N-terminal sequence of the lambda light chain corresponded to that of the V lambda III subgroup. The heavy chain of the same IgM RF clone had a blocked N-terminus, but a cyanogen bromide peptide starting after methionine at position 82 showed a sequence typical of the VHIII subgroup. Heavy and light chains were also prepared by gel filtration after reduction and carboxymethylation from the same EBV clone made into a hybridoma. After this preparation, the heavy chain was not blocked and the N-terminal sequence confirmed that the heavy chain variable region belonged to the VHIII subgroup. We believe this to be the first amino acid sequence study of a monoclonal RF derived from the repertoire of an RA patient.

Amino Acid Sequence↗
PubMed1992

[The effect of gold salts on rheumatoid factor dynamics in patients with rheumatoid arthritis].

The aim of research was to establish effect of gold-salts (under protected name "Tauredon" Byk Gulden) on the dynamics of rheumatoid factor, decreed with Waaler-Rose test, at patients with rheumatoid arthritis. Following the dynamics of rheumatoid factors was performed during 6 months continued application of "Tauredon" on a group of patients with certain diagnosis of rheumatoid arthritis. The group consisted of 8 men and 35 women, with age profile of 50 years. With continuous observation of patients and their laboratory findings (Waaler-Rose test) in regular time intervals it was found out that "Tauredon" has significant influence on oscillation of rheumatoid factor, decreed by the method of hemaglutination of sheep erythrocytes.

Adult↗