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PubMed1992

Re-evaluation of ELISA and latex agglutination test for rheumatoid factor detection in the diagnosis of rheumatoid arthritis.

An indirect ELISA for the determination of each isotype (IgM, IgG, IgA, IgD, IgE) of rheumatoid factors (RF) was performed with sera obtained from 77 patients with either classical or definite rheumatoid arthritis (RA) and 319 controls, using rabbit IgG as the antigen. The results were compared with those of a commercial latex agglutination test, using denatured human gamma globulin as the antigen for rheumatoid factor determination. At the cut-off level at which positive results were found in less than 5% of normal controls, ELISA for IgM RF determination had sensitivity, specificity, efficiency, positive predictive value and negative predictive value of 46.75%, 98.12%, 88.13%, 85.71%, 88.41%, while those for IgA RF were 46.75%, 93.42%, 84.34%, 63.16%, 87.91% and for IgG RF were 59.74%, 92.16%, 85.86%, 64.78%, 90.46%, respectively. These indices by latex agglutination test were 83.11%, 93.73%, 91.67%, 76.19% and 95.83%, respectively. IgD RF titre greater than or equal to 1:5 was detected in 19/77 RA patients and 4/200 normal controls while IgE RF titre greater than or equal to 1:5 was detected only in 7/77 RA patients. Thus, ELISA did not appear to have any advantage over latex agglutination test for diagnosis of RA.

Arthritis, Rheumatoid↗
PubMed1983

Complement-activating rheumatoid-factor-containing complexes in patients with rheumatoid vasculitis.

The role of complement and rheumatoid factor in immune complexes was examined in patients with a variety of rheumatic diseases. This was done by assessing the amount of rheumatoid factor (RF) bound from sera by F(ab)2 anti-C3 attached to a solid matrix. High levels of RF bound to C3 were detected in patients with rheumatoid arthritis complicated by vasculitis but rarely and in lower levels in patients with synovitis, ankylosing spondylitis, and systemic lupus erythematosus. The activity was bound to anti-C3 through anti-C3 antibodies because little was bound by normal F(ab)2 and was evidently complexed in the sera before in-vitro testing, since it was precipitated by 2 . 5% polyethylene glycol and sedimented with high molecular weight material on sucrose density gradient ultracentrifugation. It is considered that RF-containing complexes are present in vasculitic sera and have the potential to bind complement in vivo.

Antigen-Antibody Complex↗
PubMed1987

[Rheumatoid factors. Isotypes and severity of rheumatoid polyarthritis].

The immuno-enzymatic method permits the separate study of rheumatoid factors (RF): IgM as well as IgG, IgA, IgE, IgD. In 43 patients with rheumatoid polyarthritis (RP), classic or definite, we have studied the correlations between the various parameters of articular and extraarticular activity of RP and the levels of each isotype of RF. A statistically significant correlation of the articular activity was found with RF IgG (p less than 0.01), RF IgA (p less than 0.01). As compared to RP without rheumatoid nodule, RPs with rheumatoid nodules presented a level of RF IgM (p less than 0.05), RF IgG, IgA, IgE (p less than 0.01) which was statistically higher; a statistically significant correlation was found between haptoglobin levels and those of RF IgG (p less than 0.01). A negative correlation, statistically significant, was found between CH 50 and the levels of RF IgM. This study confirms previous studies which were carried out with an immuno-enzymatic method of detection of RF isotypes.

Arthritis, Rheumatoid↗
PubMed1981

IgG rheumatoid factor, complement and immune complexes in rheumatoid synovitis and vasculitis: comparative and serial studies during cytotoxic therapy.

IgG and IgM rheumatoid factors (IgG-RF and IgM-RF), complement and three assays for immune complexes were measured in 22 patients with rheumatoid arthritis (RA) complicated by either chronic active synovitis or vasculitis. Patients with vasculitis had relatively inactive arthritis but had higher titres of rheumatoid factors, especially IgG-RF, anticomplementary activity (ACA) and lower levels of C4 than those with synovitis. Clq-binding and platelet aggregation (PA) levels were similar in both groups. Serial measurements during cytotoxic therapy showed a close temporal relationship between the clinical features of vasculitis and levels of IgG-RF, ACA and C4 both with remission and with relapse. We suggest that immune complexes containing IgG-RF which activate complement and are detected by ACA are useful markers of rheumatoid vasculitis and may be important in its pathogenesis.

Antigen-Antibody Complex↗
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↗
PubMed1989

[Clinico-diagnostic significance of rheumatoid factors of different classes in rheumatoid arthritis].

Enzyme immunoassay was used to measure the content of rheumatoid factors (RF) of the M, A, and G classes in the blood sera of 111 patients with rheumatoid arthritis, 30 patients with osteoarthrosis deformans, and 60 donors. The ranges of normal values for each RF class were defined. The levels of all the three RF classes were significantly higher in the patients with rheumatoid arthritis vs. the reference groups. IgM, IgA, and IgG RF were regularly elevated in the patients with rapidly progressing rheumatoid arthritis and with visceritis, whereas IgM and IgG RF levels were increased in those with the maximal activity of the disease. RF of various classes are more often detectable by the enzyme immunoassay than by the Vaaler-Roset's or latex agglutination tests.

Adolescent↗
PubMed1979

Quantitation of rheumatoid factor activity by nephelometry.

Rheumatoid factor activity can be quantitated by use of nephelometric assay system. The data presented show a good correlation between this new method and the older quantitative latex tube rheumatoid factor test. In addition, the nephelometric and latex tube testing of sera from normal, rheumatoid and non-rheumatoid patients yielded similar results, suggesting the two procedures share a similar immunologic specificity. The new nephelometric test for rheumatoid factor is simple to perform, endpoints are objectively determined, and test data are highly reproducible.

Colorimetry↗
PubMed1977

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↗
PubMed1992

Nucleotide sequence analysis of rheumatoid factors and polyreactive antibodies derived from patients with rheumatoid arthritis reveals diverse use of VH and VL gene segments and extensive variability in CDR-3.

The heavy and light chain nucleotide sequences of 17 monoreactive and polyreactive rheumatoid factors largely derived from the inflamed synovial tissue of two patients with rheumatoid arthritis are described. Some of these sequences have been the subject of a previous report from our laboratories. Additionally, a few rheumatoid factors from the peripheral blood of patients with systemic lupus erythematosus and Sjogren's syndrome as well as a normal individual are included. A review of our previous results as well as the new data provided within this paper lead to the following major conclusions: (1) Rheumatoid factors and polyreactive antibodies derive from a diverse array of VH and VL gene segments; (2) While many rheumatoid factors and polyreactive antibodies are direct or nearly direct copies of germline genes, some show clear evidence of somatic mutation; (3) The CDR3 of all of these antibodies is extraordinarily diverse in length and composition. Certain 'restrictions' do appear in this very large sample: (a) the polyreactive antibodies are exclusively lambda, and (b) there seems to be a preponderance of a particular subset of VH3 genes beyond that one would expect based on random utilization.

Amino Acid Sequence↗
PubMed1982

IgE and IgE-rheumatoid factors in circulating immune complexes in rheumatoid arthritis.

The sera of 21 patients with rheumatoid arthritis (RA), 11 patients with systemic lupus erythematosus (SLE), and 20 healthy subjects were analysed for the presence of IgE in immune complex fractions. These fractions were isolated by polyethylene glycol precipitation and gel filtration. Thirteen sera from RA patients contained IgE immune complexes (IC) and 11 of these were from patients with extra-articular manifestations. One SLE and none of the control sera contained such material. The serum IgE level did not correlate with IgE content of the IC fractions. Higher mean serum IgE levels were found in RA patients with extra-articular complications than in controls or RA patients with joint disease only, but the differences did not reach statistical significance. IgE anti-rabbit IgG (IgE rheumatoid factors) could be demonstrated in some IgE positive IC fractions. Antibodies to IgE, in 2 instances characterised as belonging to IgG class, were also found in ICs. This suggests the presence of anti IgE complexes. It is suggested that IgE, including some with rheumatoid factor activity, is contained in complexes which may be involved in some extra-articular manifestations of RA.

Antibodies, Anti-Idiotypic↗
PubMed1985

Rheumatoid factor seroconversions in relation to clinical rheumatoid arthritis.

Two blood samples were taken with an interval of five years in a continuing epidemiological study of a rural population with an age range of 40-64 at the commencement. Paired sera from 1805 subjects were tested for rheumatoid factors using Waaler-Rose and latex tests. Simultaneous conversion in both tests from negative to positive occurred in seven cases and from positive to negative in eight cases, corresponding to 20% of the Waaler-Rose positives. The mean Waaler-Rose titre in the cases converting to positive was nearly four times higher than in the cases converting to negative. Five subjects developed Waaler-Rose-positive rheumatoid arthritis after the baseline survey. In three of them, positive rheumatoid factor reactions were observed to precede the joint disease; in two others the chronological order could not be established.

Adult↗
PubMed1995

The use of rheumatoid factors in clinical practice.

Rheumatoid factor is a commonly requested test in the investigation of joint problems. Although the test has been found to be both sensitive and specific for rheumatoid arthritis in patients attending Rheumatology Clinics, when the test is applied to general hospital or community populations it performs poorly. Thus the setting in which rheumatoid factor tests are requested and awareness of the test's limitations are critical for appropriate use and interpretation of results. We studied 295 consecutive requests for testing at four centres. The majority were performed for the investigation of joint problems but only 6% of these were positive, suggesting unselective requesting. Half of the results were used to make diagnoses and influence management. However, significant numbers of clinicians felt that the test result had either excluded or confirmed a diagnosis of rheumatoid arthritis suggesting that results were being over-interpreted and that clinical decisions made on this basis may have been inappropriate. We conclude that in this setting rheumatoid factor testing is of limited value and generates misleading information.

Adolescent↗
PubMed1981

Specificity of hidden 19S IgM rheumatoid factor in patients with juvenile rheumatoid arthritis.

Hidden 19S IgM rheumatoid factors (RF)-i.e., RF detected in the IgM-containing fraction after separation of the serum at an acid pH-have been found in 68% of patients with seronegative juvenile rheumatoid arthritis (JRA). Inhibition studies utilizing a hemolytic assay for RF were performed to determine the specificity of hidden 19S IgM RF. Sera from 14 children with JRA were separated by gel filtration at pH 4.05. Two were seropositive for RF and 12 were seronegative; the latter had high titer hidden 19S IgM RF. The IgM-containing fractions were preincubated with monomeric human IgG, rabbit IgG, or bovine IgG, and the complement-dependent hemolytic assay ws performed. The RF in the IgM fraction from the 2 seropositive patients were inhibited most strongly by rabbit IgG, whereas hidden RF in the IgM fraction of 9 seronegative patients were inhibited markedly by human IgG (homologous IgG equal to autologous IgG), poorly by rabbit IgG, and not at all by bovine IgG. Further inhibition studies with the hidden 19S IgM RF demonstrated inhibition by the human IgG1 subclass in all patients and only minimal inhibition by the IgG3 subclass in 3 patients. Inhibition with IgG1 Fc fragments produced by papain and thermolysin digestion demonstrated inhibition by only those fragments that contained the G1m (a) antigenic area which is found in the C gamma 3 homology area of the IgG1 molecule. These data indicate that hidden 19S IgM RF possibly circulate as immune complexes bound to the IgG1 molecule and the binding chiefly occurs in th G1m (a) homology area.

Arthritis, Juvenile↗
PubMed2003

[A basic study of determination matrix metalloproteinase-3 and carbohydrate in rheumatoid factor in serum for diagnosis of rheumatoid arthritis].

The examination of rheumatoid factor (RF), one of the diagnostic marker of rheumatoid arthritis (RA), showed negative about 25% of patients with RA. We analyzed a matrix metalloproteinase-3 (MMP-3) and a carbohydrate in rheumatoid factor (CA.RF) for diagnosis of RA: the former is used the kit "Panaclear MMP-3[Plate]" and the latter is used the kit "Picolumi CA.RF". The basic study of these reagents showed satisfactory results. In 73.3% of seronegative RA showed positive on both MMP-3 and CA.RF levels in serum, respectively. We found that these examinations might be useful for diagnosis of RA, especially during seronegative RA.

Adult↗
PubMed1989

Cross-reactive antiidiotypic antibodies against human rheumatoid factors from patients with juvenile rheumatoid arthritis.

We prepared antiidiotypic (anti-Id) antibody to 2 polyclonal IgM rheumatoid factors (IgM-RF) and 2 polyclonal "hidden" IgM-RF. The anti-Id antibodies were isolated by chromatography on Sepharose 4B, to which was bound rabbit anti-human IgG Fc fragments. F(ab')2 fragments from the anti-Id antibodies were generated by pepsin digestion and isolated by gel filtration. The anti-Id antibodies directed against RF from 4 patients with juvenile rheumatoid arthritis (JRA) were tested by an inhibition hemolytic assay for cross-reactivity with IgM-RF from 4 adult patients with rheumatoid arthritis, 6 patients with JRA, and 13 JRA patients with hidden RF. The 4 anti-Id antibodies had variable cross-reactivity with the isolated adult RA RF, JRA RF, and JRA hidden RF. Similar results were obtained by a direct-binding enzyme-linked immunosorbent assay for the anti-Id antibodies. The broad pattern of cross-reactivity was apparently unrelated to a particular amino acid sequence, but was associated with the antigen-binding site of IgM-RF. These results suggest the possibility that the anti-Id antibodies prepared against isolated RF obtained from JRA patients bear the "internal image" of antigen; that is, the Fc region of human IgG. These anti-Id antibodies may be generated in JRA patients and may possess specific immunomodulatory properties.

Animals↗
PubMed1995

Rheumatoid factor avidity in patients with rheumatoid arthritis: identification of pathogenic RFs which correlate with disease parameters and with the gal(0) glycoform of IgG.

The standard ELISA for measuring rheumatoid factor (RF) binding was modified by treatment after the RF-Fc interaction with 2 M guanidine, which allowed a measurement of the avidity of the interaction. Incubation with 4 M guanidine eliminated RF binding. There was a direct correlation (r = 0.99) between the avidity as measured by the modified guanidine ELISA, and the dissociation constant for monoclonal RFs, as measured by competitive ELISA. Of the seropositive rheumatoid arthritis (RA) patients tested, 47% had high-avidity RFs (> or = 8% RF binding remaining after guanidine treatment). Tender joint count scores were significantly higher in the high avidity group (p = 0.05), whereas there was no significant difference in the ages, disease duration, sedimentation rate, RF titer or serum Ig levels compared to those with low-avidity RFs. Additionally 58% of those with high-avidity RFs had subcutaneous nodules, compared to 40% of the low-avidity group. A significantly higher number of nodules was present in the high-avidity RF group compared to those with low-avidity RFs (p = 0.03). Interestingly, the RF avidity was significantly higher in isolated immune complexes (IC), compared to that in circulating IgM RFs (p = 0.01). The RF avidity correlated with the presence of the glycoform of IgG lacking galactose in both circulating and IC-derived IgG (p = 0.003 and 0.009 respectively). Information about the strength of binding to Fc identifies a subgroup of IgM RFs that are likely pathological in patients with RA, as well as a specific glycoform of the target antigen.

Antibodies↗
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↗