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PubMed1987

Human rheumatoid factor crossidiotypes. II. Primary structure-dependent crossreactive idiotype, PSL2-CRI, present on Wa monoclonal rheumatoid factors is present on Bla and other IgM kappa monoclonal autoantibodies.

The amino acid sequence of the L-CDR2 (complementarity-determining region) of Bla mRF (monoclonal rheumatoid factor) is identical to that of the Wa mRFs. The PSL2-CRI (crossreactive idiotype), as determined by anti-PSL2, which has been shown to be present on all Wa mRFs, is also present on the Bla mRF and other monoclonal autoantibodies. PSL2-CRI is, therefore, not unique to Wa mRFs and may be present on most IgM kappa monoclonal autoantibodies. Whether PSL2-CRI is a crossidiotype (XId) that is selectively present on autoantibodies or represents an allotypic marker for a V kappa III gene is undetermined.

Amino Acid Sequence↗
PubMedDate not supplied

The photometric latex test for rheumatoid factors in patients with rheumatoid arthritis. II. Clinical evaluation.

The photometric latex test (PLT) for the detection of rheumatoid factors has been clinically evaluated. PLT titers have been closely studied in relation to clinical and laboratory parameters by means of parametric and nonparametric statistical methods. An analysis of the sensitized sheep cell test (SSC) titers has also been undertaken. The subjects comprised 377 patients with rheumatoid arthritis (RA) and 120 controls. The medical data recorded included sex, age, diagnosis, anatomical stage, functional class, duration and course of the disease, presence of the American Rheumatism Association (ARA) criteria, blood sedimentation rate, red and white blood counts, haemoglobin concentration, total protein content, serum protein levels, and SSC and PLT titers. A multivariate stepwise regression analysis with eight normally distributed variables was made. In accordance with previous findings, a significant correlation was shown to exist between the serum protein levels and the development of the RA when the anatomical stage, functional class and course of the disease were used as parameters of disease activity. In the RA patients there was also correlation between the serologic titers and the serum protein levels, and the anatomical stage, functional class and course of the disease, and the sedimentation rate, thus showing that titers can also serve as a measure of the inflammatory process. There was a significant correlation between the number of ARA criteria and the titers in the RA patients but not in the controls. The course of the disease correlated with the serum titers and other inflammatory parameters, a finding showing that the course of the disease is an important diagnostic parameter with possible prognostic value. Correlation was also demonstrated between the white blood count and the titers. It is concluded that the sedimentation rate, albumin and gamma-globulin levels, and PLT titer are the best parameters of disease activity. The titer values are not only of diagnostic importance but have prognostic value as regards the severity of the disease.

Adolescent↗
PubMed1987

Rheumatoid factors from patients with rheumatoid arthritis possess private repertoires of idiotypes.

Considerable interest has focused on idiotypic cross-reactivity among antibody molecules. Cross-reactive idiotypes (Id) on monoclonal and polyclonal rheumatoid factors (RF) have been found frequently. Sufficient attention has not been directed, however, to the proportion of RF exhibiting the cross-reactivity, leaving the impression of extensive RF cross-reactivity when, in fact, this might represent a small minority of total RF molecules in a given individual. We have examined the polyclonal RF from patients with rheumatoid arthritis (RA) for cross-reactive Id in three different assays and with different Id-anti-Id systems. First, a sensitive liquid-phase radioimmunoassay was used in which panels of sera were tested for inhibition of different, idiotypically unrelated, Id-anti-Id interactions. When compared with normal sera, some of the sera from patients with RA caused minimal inhibition of Id-anti-Id interactions. None, however, caused marked inhibition of any Id-anti-Id system. Secondly, the panels of sera were also tested in a direct binding ELISA to detect partially cross-reactive Id that may not have been identified in the inhibition radioimmunoassay without differing results. Finally, results similar to the autologous Id-anti-Id inhibition assay were also found when the panels of RA sera were tested in two nonautologous Id-anti-Id systems, in which the anti-Id reacted with other than their own Id. These studies indicate that although cross-reactivity with some RF of an individual's total RF population may be seen frequently, an individual's repertoire of RF is itself private, quite diverse, and unique to that individual.

Antibodies, Anti-Idiotypic↗
PubMed1985

Spontaneous and aggregated IgG induced rheumatoid factor producing cells in rheumatoid arthritis.

Seropositive rheumatoid arthritis (RA) patients were found to have high numbers of spontaneously occurring cells making rheumatoid factor (RF) reactive with human IgG as measured by a RF plaque forming cell (RF-PFC) assay. There was a significant positive correlation between the number of RF-PFC and both disease activity measured by the sedimentation rate and RF titer measured by the RA latex test. Aggregated IgG and pokeweed mitogen were equally effective stimulators of RF-PFC in cultures of RA peripheral blood mononuclear leukocytes. The rheumatoid ratio of helper (T4): suppressor (T8) T lymphocytes was also significantly increased over the ratio of normal controls, but this ratio did not correlate with the number of RF-PFC. Aggregated IgG or immune complexes may be responsible for stimulating RA RF-PFC in vivo.

Adult↗
PubMed1977

The effect of fenoprofen calcium (Nalfon) on levels of rheumatoid factor in patients with rheumatoid arthritis.

In 88.9% of a group of 18 patients with rheumatoid arthritis participating in an open-label study with fenoprofen calcium (Nalfon), there was observed a mean titre decrease in level of rheumatoid factor as compared to baseline levels. In follow-up, three months to one year later, a uniform titre increase above the mean level of the study period had occurred. In all cases the titre returned to baseline levels or higher.

Arthritis, Rheumatoid↗
PubMed1984

Enhanced T helper cell function for the spontaneous production of IgM rheumatoid factor in vitro in rheumatoid arthritis.

Co-culture experiments between T and B cells from normal subjects and rheumatoid arthritis (RA) patients were performed in order to assess the immunoregulatory effects of T cells on spontaneous production of IgM rheumatoid factor (IgM-RF). Cultures of normal B cells with normal, autologous or allogeneic T cells failed to synthesize IgM-RF. In contrast, RAT cells promoted IgM-RF production from normal B cells as well as from RA B cells. The 'helper' effect of T cells from RA patients for IgM-RF production was not HLA-DR4 restricted and could not be accounted for by an allogeneic effect. These observations suggest that activated T helper cells may contribute to the production of IgM-RF in RA.

Arthritis, Rheumatoid↗
PubMed1990

Significance of rheumatoid factor isotypes in seronegative rheumatoid arthritis.

In a cross-sectional study of 124 patients with definite or classical rheumatoid arthritis (RA) and negative agglutination assays, rheumatoid factor (RF) isotypes were measured using an ELISA technique. Elevated levels of IgA-RF were found in 55 patients (44%), IgG-RF in 99 (80%), and IgM-RF in 20 (16%). The levels of IgA- and IgM-RF correlated with each other (P less than 0.001). Elevated levels of IgM-RF were associated with a more severe disease course. Elevated levels of IgA-RF correlated with the occurrence of bone erosions. The results of this study suggest that in patients with RA and negative agglutination assays, both IgM- and IgA-RF are markers of disease severity.

Adult↗
PubMed1988

Quantitation of IgM, IgA and IgG rheumatoid factors by ELISA in rheumatoid arthritis and other rheumatic disorders.

We describe the evaluation of an enzyme-linked immunosorbent-assay (ELISA) for the measurement of IgM, IgA and IgG rheumatoid factor (RF). Results were obtained from sera of normal controls and patients with different rheumatic disorders in a cross-sectional study. Both human and rabbit IgG could be used as antigen in the assays. IgA-RF and IgG-RF were measured after pepsin digestion. The WHO reference preparation was used to standardise IgM-RF, but could not be used in the IgA- and IgG-RF assay, because neither IgA- nor IgG-RF could be detected in this standard serum. The ELISA for detection of RF is a highly sensitive and reproducible method and quantitation of results can be standardised. It yields good discriminative values for RA versus controls, in particular when more RF-isotypes are determined. In RA patients a correlation between IgM-, IgA- and IgG-RF concentrations does exist, although a wide variation was found in the ratio of these concentrations.

Adult↗
PubMed1996

Determination of IgA- and IgM-rheumatoid factors in patients with rheumatoid arthritis with and without nephropathy.

OBJECTIVE: To clarify the characteristics and pathogenesis of renal disorders in patients with rheumatoid arthritis (RA). METHODS: In this study, 143 patients with RA were included, from whom 43 with urinary abnormalities were biopsied. Serum rheumatoid factor (RF) concentrations of IgA and IgM isotypes were also measured in these patients by enzyme linked immunosorbent assay. RESULTS: Light microscopy of renal biopsy specimens showed minor glomerular abnormalities in six patients, mesangial proliferative glomerulonephritis (GN) in 21, membranous nephropathy in seven, renal amyloidosis in seven, and tubulointerstitial nephritis in two. Twelve patients with mesangial proliferative GN and one with minor glomerular abnormalities were found by immunofluorescence microscopy to have abnormalities consistent with IgA GN. Although the concentrations of IgA-RF in patients with IgA GN were slightly raised compared with those with glomerulopathy established by biopsy but not associated with IgA GN, the concentrations of IgA-RF were higher in patients with RA with vasculitis or interstitial pneumonia than those with RA complicated by IgA GN. CONCLUSIONS: Mesangial proliferative GN, including IgA GN, may be a frequent renal lesion in Japanese patients with RA. IgA-RF may play little pathogenetic part in the development of IgA GN in RA.

Adult↗
PubMed2004

Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects.

OBJECTIVES: Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure. METHODS: A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978 and 1980. Detailed histories of smoking and RF (sensitized sheep cell agglutination test) were obtained in the basic examination. In 2000, serum cotinine and thiocyanate were determined from serum samples collected at baseline and stored at -20 degrees C. A cut-off point of 100 microg/l was used for serum cotinine and 10 micromol/l for thiocyanate to indicate active smoking. RESULTS: There was a close association between smoking and strongly positive RF. After adjustment for age, sex, coffee consumption and region, the odds ratios (95% confidence intervals in brackets) in current smokers and in those who had quit smoking were 3.94 (2.04-7.61) and 2.71 (1.33-5.53), respectively, compared with those who had never smoked. Among current smokers, the intensity, duration or tertiles of pack-years of smoking were not related to RF. No relationship between serum cotinine or thiocyanate and RF positivity was observed within the subgroups of current smokers and those who had quit. Among those who reported that they had never smoked but who nevertheless had serum cotinine levels at least 100 microg/l, the adjusted odds ratio of strongly positive RF was 4.48 (1.48-13.50) compared with people who had never smoked and whose serum cotinine levels were less than 100 microg/l. CONCLUSIONS: The results are not in line with the hypothesis of a dose-response relationship between smoking exposure and RF positivity.

Adult↗
PubMed2000

Evidence that human immunoglobulin M rheumatoid factors can Be derived from the natural autoantibody pool and undergo an antigen driven immune response in which somatically mutated rheumatoid factors have lower affinities for immunoglobulin G Fc than their germline counterparts.

The question of whether immunoglobulin (Ig)M rheumatoid factors (RF) arise as the result of an abnormal expansion of already existing clones producing natural autoantibodies or emerge as new clones that are somatically mutated owing to an antigen driven immune response has never been conclusively answered. In this study, an inhibition ELISA was utilized to measure the affinities of recombinant antibodies using VH segments reverted back to their closest germline counterparts (germline revertants). In all cases, the somatically mutated parental RFs had a decreased affinity for immunoglobulin (Ig)G Fc compared to the germline revertant, indicating that the antibodies in the germline configuration had the higher affinities. This demonstrates that somatic mutation is not a prerequisite to generate disease associated antibodies. The presence of mutations in the parental IgM RFS suggests that these cells had been involved in a germinal centre reaction. As the germinal centre is the conventional site of the acquisition of mutations during an antigen driven response, these data suggest a role for germinal centres in the generation of the antibody diversity in addition to the selection of higher affinity antibodies. Assuming that only antigen selected cells survive deletion, these data support the hypothesis that IgM RFS can be derived from the natural autoantibody repertoire and result from an antigen driven response. Mechanisms controlling the survival of B cells based on the affinity/avidity of the immunoglobulin receptor are shown to be functional in patients with rheumatoid arthritis.

Amino Acid Sequence↗
PubMed1987

[Isotypes of rheumatoid factors and cellular immunity anomalies in rheumatoid polyarthritis. Apropos of 61 cases].

In 61 patients with rheumatoid polyarthritis, we studied the rheumatoid factors isotypes, class IgM, IgG, IgA and the abnormalities of the ratio CD4/CD8 (lymphocytes with membrane phenotype "helper"/lymphocytes with membrane phenotype "suppressor") determined by monoclonal antibodies. We found a statistically significant increase of the rate of IgM rheumatoid factors (p less than 0.0001), IgG (p less than 0.004), IgA (p less than 0.008), in patients with rheumatoid polyarthritis whose ratio exceeded that of the control population. On the other hand, the percentage of rheumatoid factors detected by agglutination was not significantly increased in this group. This increase seemed linked to a specific abnormality of the control of lymphocytes B which synthesize rheumatoid factors.

Adult↗
PubMed1997

Relations between absolute number of CD4 + CD29+ memory cells and levels of interleukin-6, rheumatoid factors, and acute phase proteins in rheumatoid synovial fluid.

Synovial fluid samples from 21 rheumatoid arthritis patients were analyzed for lymphocyte subsets using flow cytometry and antibodies to the lymphocyte surface antigens CD3, CD4, CD8, CD16, CD19, CD29, and CD45RA. Synovial fluid levels of interleukin-6, rheumatoid factors and acute phase proteins were also measured. Depletion of CD45RA+ cells and predominance of CD29+ cells were found. Interleukin-6 levels were markedly elevated (1155 pg/ml; range, 24-3875 pg/ml), as were levels of IgM, IgG and IgA rheumatoid factors and of acute phase proteins. CD4 + CD29+ counts were significantly correlated with interleukin-6 levels. Interleukin-6 levels were significantly correlated with levels of all three rheumatoid factor classes but not with levels of acute phase proteins. Significant correlations were also found between CD19+ B counts and levels of all three rheumatoid factor classes. These data suggest that synovial fluid CD4 + CD29+ cells may be involved in the immune dysregulation characteristic of rheumatoid arthritis. The correlation between CD4 + CD29+ counts and interleukin-6 levels is consistent with the recent hypothesis that, together with monocytes, CD4 + CD29+ cells are an important source of the elevated levels of interleukin-6 seen in rheumatoid synovial fluid.

Acute-Phase Proteins↗
PubMed2000

Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis.

OBJECTIVES: Smokers have an increased incidence of rheumatoid factor (RF) and rheumatoid arthritis (RA) and one report has also indicated that smoking may also adversely influence the severity of RA. METHODS: Sixty-three women with advanced RA answered a structured questionnaire that included detailed information about their smoking history. The women were also evaluated clinically and radiologically. RESULTS: Heavy smoking (>/= 20 pack-yr) was associated with rheumatoid nodules (P: = 0.01), a higher HAQ score (P: = 0.002) and a lower grip strength (P: = 0.01). Smoking was also associated with more radiological joint damage (P: = 0.02). A positive correlation was observed between smoking and RF levels, in particular IgA RF and a combined elevation of IgM and IgA RF. CONCLUSIONS: Smoking has an adverse effect on disease progression in patients with RA. An association was also observed between smoking and those RF types that predispose to RA and have the highest diagnostic specificity for this disease.

Adult↗
PubMed1981

IgG rheumatoid factor. Detection by enzyme immunoassay in rheumatoid arthritis and normal subjects.

IgG rheumatoid factors were demonstrated by enzyme immunoassay using, as antigen, goat antibodies to human serum albumin in the form of immune complexes. Elevated levels of IgG rheumatoid factor were noted in the majority of patients with seropositive rheumatoid arthritis but also relatively often in normal blood donors. Reactivity of IgG rheumatoid factor was in most instances inhibitable by IgG from various species, including man. Exceptionally, restricted specificity towards IgG from bovidae, was recognized.

Adult↗
PubMedDate not supplied

In vitro production of monoclonal human rheumatoid factors.

Lymphocytes from rheumatoid arthritis patients have been fused with drug-marked human myeloma cell lines and hybrids selected which secrete rheumatoid factors. Limiting dilution and soft agarose plates have been used to clone these hybrids, but so far stable clones have not been obtained. Epstein-Barr virus has been used to transform lymphocytes, and clones which secrete rheumatoid factors have been obtained.

Arthritis, Rheumatoid↗