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Rheumatoid factor plaque-forming cells in rheumatoid synovial tissue.

Cells producing rheumatoid factor (RF) were readily detected in vitro by means of a haemolytic plaque assay system employing sheep erythrocytes (SRBC) sensitized with reduced and alkylated rabbit IgG anti-SRBC antibody as target cells. Rheumatoid factor-producing, plaque-forming cells (RF-PFC) were observed in all of the synovial tissue cell preparations from seropositive rheumatoid arthritis patients studied. The numbers of RF-PFC varied considerably without any direct correlation with serum titres of RF antibody activity. However, high numbers of RF-PFC were never found in patients with low rheumatoid factor titres whereas, high and low numbers of RF-PFC were found among the patients with high RF titres. Synovial tissue cell preparations from a group of seronegative patients, with only one exception, failed to exhibit RF-PFC.

Adolescent

IgG-, IgM- and IgA-rheumatoid factors in healthy adults and rheumatoid patients determined by an indirect immunofluorescence method.

Sera from 173 healthy adults and 55 rheumatoid patients were studied for IgG-, IgM- and IgA-rheumatoid factors (RFs) by a modification of Este's indirect immunofluorescence method. Rabbit IgG bound to smeared sheep red cells was used as antigen. With each serum tested a smear on non-sensitized cells was used as control antigen. Anti-IgG of the sera studied, binding to the antigen, was demonstrated by fluorescein-conjugated antisera, monospecific for gamma, mu and alpha chains, and not containing antibodies to sheep erythrocytes or rabbit IgG. Positive reactions were obtained with IgG as antigen, but not with the F(ab')2 fragment. The sera tested were treated with dithiothreitol before they were assayed for IgG-RF, in order to abolish false-positive reactions due to IgM-RF activity. The detection limit for IgM-RF was 1 IU per ml. IgM-RF titres of 9 occurred in 7% of healthy adults and 73% of rheumatoid patients, titres greater than or equal to 18 in 3.5% and 67% respectively. IgG-RF titres of 9 occurred in 9% of healthy adults, 21% of seronegative and 24% of seropositive rheumatoid patients. Titres of 18 occurred in 3% of healthy adults and in 14% of seronegative rheumatoid patients. Titres of greater than or equal to 18 occurred in 22% of seropositive rheumatoid patients. IgG-RF was correlated with an involvement of more than 20 joints. IgA-RF was found in 83% of seropositive, 11% of seronegative rheumatoid patients and in none of the healthy adults (serum dilution 1:9).

Adult

[Rheumatoid factor in systemic lupus erythematosus].

1. Rheumatoid factors were found in 12 of a total of 105 SLE patients. 2. Rheumatoid factors were found especially in patients with additional chronic polyarthritis, whereas it was not possible to find a relation between these factors and the age of patients and the duration of disease, respectively. 3. There was no difference between SLE and progressive polyarthritis as regrads the cold precipitation of rheumatoid factors. 4. In vitro fixation of the complement to antinuclear factors was not hindered by rheumatoid factors. 5. Renal lesions and uremia were observed in SLE patients with and without rheumatoid factors, the percentages being roughly the same in the two groups.

Adolescent

[Modifications in alpha 2 globulins, gamma globulins and in rheumatoid factor during gold salt therapy in rheumatoid arthritis].

A total dose of g 1.071, given as hydrosoluble salts for a 12 month period, showed a significant decrease in serum gamma globulins along with clinical improvement in 17 patients affected with rheumatoid arthritis. A decrease in alpha 2 globulins and in rheumatoid factor titre was observed too, but it was not significant. The data suggest that in rheumatoid arthritis the gold therapy might also be effective on the immunological disease mechanism.

Adult

Radioimmunoassay of IgG and IgM rheumatoid factors reacting with human IgG.

Although IgG rheumatoid factor may play a central role in the pathogenesis of rheumatoid arthritis, previously there have been no precise methods for its specific measurement in serum and synovial fluid. This paper describes a solid phase radioimmunoassay for the independent quantification of IgM and IgG rheumatoid factor reacting with the Fc fragment of human IgG. As measured by this assay, serum IgG rheumatoid factor levels differed significantly between patients with seropositive and seronegative rheumatoid arthritis and normal control subjects. In addition, several sera and joint fluids from patients with seropositive rheumatoid arthritis, even without vasculitis, were shown by gel chromatography to have acid-dissociable complexes of IgG rheumatoid factor suggestive of IgG-IgG dimer or trimer formation.

Alkylation

IgA rheumatoid factor in the sera and saliva of patients with rheumatoid arthritis and Sjögren's syndrome.

With a sensitive radioimmunoassay we have found elevated IgA rheumatoid factor (IgA-RF) levels in the sera of patients with rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus. The IgA--RF showed a pattern of reaction with human IgG subclasses and animal gammaglobulins similar to that of IgM-RF from the same patients. Rheumatoid factors of both classes were shown to be present in saliva of patients with rheumatoid arthritis and Sjögren's syndrome.

Arthritis, Rheumatoid

A study of the variable heavy chain (VH) regions in human polyclonal IgM rheumatoid factors.

Ten IgM polyclonal rheumatoid factor (RF) preparations isolated from sera from various patients with rheumatoid arthritis (RA) were investigated with respect to their variable heavy chain (VH) subgroups. They were tested in a haemagglutination inhibition system using red cells sensitized with myeloma proteins with known chemical VH subgroups and anti-VH subgroup specific antisera. Most of the preparations showed a considerable degree of restriction to one VH subgroup. Seven of the IgM-RF preparations were restricted to the VHIII subgroup, two to the VHI subgroup and one to the VHII subgroup. However, a weak reaction in other VH subgroup systems was seen in several instances. Two normal IgM fractions from healthy persons showed no VH subgroup restriction, and showed a rather similar degree of reaction in all the three subgroup systems.

Arthritis, Rheumatoid

A simple routine method for detecting hidden rheumatoid factors.

A new and simple routine method is described for detecting hidden rheumatoid factors in human serum. EDTA glycine and NaCl were used to liberate hidden rheumatoid factors and to inactivate complement before rheumatoid-factor activity was determined in a glycine--NaCl solution. Forty-nine out of 97 sera from individuals with seronegative rheumatoid arthritis gave positive reactions by this method. Rheumatoid sera with low titres by standard tests gave higher titres with the new method. The new method detects both IgM and IgG rheumatoid factors and is simple and suitable for use in routine medical laboratories. Used in parallel with the classical tests, it facilitates detection of hidden rheumatoid factors.

Arthritis, Rheumatoid

Rheumatoid factor: correlation with recurrence in transitional cell carcinoma of the bladder.

The serum rheumatoid factor was measured by the latex fixation test in different titrations in 100 cases of bladder tumors. The rheumatoid factor was found in transitional and squamous cell carcinoma of the bladder. The percentage of positive studies correlated well with the clinical staging of the tumors. The rheumatoid factor activity also correlated with the recurrence of transitional cell carcinoma. A high recurrence rate was found when the rheumatoid factor was present in contrast to a low recurrence rate when it was absent at the initial examination. The percentage of recurrences correlated with the titration of the rheumatoid factor. The mechanism of production of the rheumatoid factor and its correlation with tumor recurrence are discussed.

Carcinoma, Squamous Cell

Immune complex detection and complement activity in rheumatoid arthritis: a comparative study of a radioimmunoassay using monoclonal rheumatoid factor, gel diffusion techniques and C4 activity.

Paired sera and synovial fluids from forty-nine patients with rheumatoid arthritis and twenty-five with other forms of arthritis were tested for immune complexes by a radioimmunoassay using monoclonal rheumatoid factor and gel diffusion procedures with monoclonal rheumatoid factor and C1q. Synovial fluid hemolytic C4 and C4 adjusted for IgG concentration were determined in both groups of patients. Immune complexes were detected at similar high frequencies in the rheumatoid synovial fluids by precipitin formation with monoclonal rheumatoid factor (68%) and C1q (71%). In contrast, immune complexes in rheumatoid sera were detected in low frequency by precipitin reactions with monoclonal rheumatoid factor (10%) and C1q (0%). Using the monoclonal rheumatoid factor radioimmunoassay, thirty-one (63%) synovial fluids exceeded the mean non-RA binding activity by one standard deviation. Similarly, twenty-four (49%) rheumatoid sera exceeded the mean non-RA binding activity to one standard deviation. Synovial fluid C4 adjusted for IgG as well as IgG alone distinguished between the two groups of patients whereas the C4 values did not. The C4/IgG value showed a strong negative correlation with the monoclonal rheumatoid factor radioimmunoassay and C1q precipitin formation.

Antigen-Antibody Complex

Rate nephelometric measurement of rheumatoid factor in serum.

We describe the measurement of rheumatoid factor in human sera with a rate nephelometer. The National Reference Preparation for Rheumatoid Factors is used to calibrate the assay in International Units. We used Hyland Positive Control, Level I, as a secondary standard. The standard curve is exponential, but is linear when plotted on log-log graph paper. Aggregated immune globulin (IgG) is the antigen used to detect rheumatoid factor (IgM-class antibody to IgG). The rate reaction measures the rate of increase in light-scatter by the antigen-antibody complexes; the reaction takes place in 17 to 20 s. Precision, linearity, and accuracy are excellent. Results agree well with those for a commonly used latex precipitation test. The advantages of speed, quantification in International Units, and superior discrimination of concentration as compared to serological titration provide a more reliable test for use in the diagnosis and treatment of rheumatoid arthritis.

Antigen-Antibody Complex

Reference preparation to standardize results of serological tests for rheumatoid factor.

The variance of between-laboratory results for rheumatoid factor tests was reduced through the use of a reference serum preparation. Two separate proficiency testing surveys have shown reduction of 58 to 81% in variance with samples of differing levels and composition. Reduction of variance was seen in data from laboratories in which the same methods and reagents were used, but greater reduction in variance was seen in results from laboratories using different methods and reagents. This study demonstrates that comparability of results of rheumatoid factor tests can be significantly improved through the use of a standard reference serum preparation and that confidence in such results can therefore be increased. A serum rheumatoid factor level of approximately 50 IU/ml is equivalent to a titer of 160 in the Singer-Plotz latex test, which has traditionally been accepted as evidence of rheumatoid arthritis.

Arthritis, Rheumatoid

Rheumatoid factors bind beta 2 microglobulin. Detection of beta 2 microglobulin-complexes in rheumatoid arthritis.

beta 2 Microglobulin binding rheumatoid factors and occurrence of complexed form of beta 2 microglobulin were found in rheumatoid arthritis (RA) by radioimmunological methods. 1. As related to the appropriate values of control sera and osteoarthritic synovial fluids, one of the six sera and five of the six synovial fluids of RA patients exhibited increased binding activity for 125I-beta 2 microglobulin, 2. Rheumatoid factors (RF) purified by means of immunoadsorbent bound beta 2 microglobulin; 3. Both 19S and 7S components of sera, synovial fluids and purified RF samples had beta 2 microglobulin binding activity, which was inhibited by an excess of unlabeled beta 2 microglobulin; 4. Complexed (3% PEG 6000 insoluble) beta 2 microglobulin was found in three of fourteen sera and in twelve of fourteen synovial fluids of RA patients. Level of complexed beta 2 microglobulin was independent of its total concentration in the original samples; 5. In the fraction of synovial fluids enriched immune complex the amount of beta 2 microglobulin was in positive correlation with quantity of RF. Presumable immunological and pathological significance of "anti-beta 2 microglobulin"-like cross-reactive RF antibodies is discussed.

Arthritis, Rheumatoid

[Methods and value of an immunofluorescence-optical determination of IgM, IgG and IgA rheumatoid factors].

Today the immuno-fluorescence technique is the simplest method to detect rheumatoid factors of all immuno-globulin classes. When applying sheep erythrocytes, standard sera may be used without exception. The airdried smear of the cells is to be incubated with rabbit anti-human-erythrocyte serum. The rheumatoid factors of the subsequently applied inactivated patients' sera localise above the amboceptor on the erythrocyte membrane. Only they bind FITC marked anti-human-gamma-globulin and cause a specific fluorescence. As a proof heteroagglutinines and crossreacting antibodies of the marked sera are first absorbed and corresponding controls are carried out. According to assessments of 101 sera approximately 20% of healthy people, approximately 50% of "definitely seronegative" patients with rheumatoid arthritis according to the agglutination method as well as 30% of other arthropathies had rheumatoid factors by these methods. A negative immunofluorescence optical test does not absolutely exclude the presence of rheumatoid factors in the serum. It is suggested that their occurrence are due to secondary reactions to the formation of immunogen antigen-antibody complexes.

Antibodies, Anti-Idiotypic

[Critical study of techniques for the detection of "light" rheumatoid factors (author's transl)].

In a number of cases of true rheumatoid arthritis, it is not possible to demonstrate the presence of 19 S "heavy" rheumatoid factors by the Waaler-Rose and globulin latex techniques. However, in some of them, 7 S rheumatoid factors are suspected. Three techniques for the detection of these "light" rheumatoid factors are described and critically evaluated. The authors report their own experience of the immuno-absorption and indirect immunofluorescence technique performed on 156 sera from RA patients. Immuno-absorption is not felt to be a reliable technique on several grounds. Indirect immunofluorescence is of value only in the diagnosis of seronegative rheumatoid arthritis where it provides information in addition to that offered by classical techniques. It is positive in 53.3% of seronegative rheumatoid arthritis sera.

Arthritis, Juvenile

Rheumatoid factor (antigammaglobulin) in women: effects of oral contraceptives use of its prevalence.

A total of 14,856 women, including 921 pregnant subjects, were tested for rheumatoid factor; 4,562 were using oral contraceptives at the time of testing. The prevalence of rheumatoid factor increased directly with age. The age-adjusted prevalence of rheumatoid factor was lower in oral contraceptive users than in nonusers but this difference was not statistically significant. Rheumatoid factor remained positive in 39% of subjects undergoing retesting after an average interval of 16 months. Those women with higher titers of rheumatoid factor were more likely to remain positive (81%). Of the women having positive tests, 5.4% were identified as having rheumatoid disease.

Adolescent

Mixed lymphocyte reaction in healthy women with rheumatoid factor. Lack of association with HLA-Dw4.

In independent studies, 51% and 36% of patients with rheumatoid arthritis have been shown to possess HLA-Dw4 compared to 7% and 13% of controls. In one study Dw4 positive patients more frequently had rheumatoid factor in their sera than did Dw4 negative patients. In order to determine if the Dw4 specificity is associated with the disease or with the presence of rheumatoid factor, the frequency of this HLA antigen has been determined in 24 healthy women known to have rheumatoid factor (median titer 1:160). Only 3 were found to have the Dw4 specificity, suggesting that this specificity is not associated with rheumatoid factor in the absence of rheumatoid arthritis.

Adult