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PubMedDate not supplied

[Levels of IgA rheumatoid factors in seropositive rheumatoid polyarthritis. Absence of correlation with disease activity or pejorative course].

Rheumatoid factors of the IgA isotype directed to human IgG Fc fragment were assayed, using an Elisa test, in the serum of 30 patients with seropositive rheumatoid arthritis and in the synovial fluid of 9 of them. A high incidence was found in the serum (90%) and synovial fluids (77%). Clinical, radiological and biological parameters of each patients were recorded at the time of the assay, and two years later. There was no statistically significant association between IgA rheumatoid factors levels and other parameters, nor with a pejorative evolution. However, a significant negative correlation was observed between IgA rheumatoid factors levels and the duration of the disease, suggesting that IgA rheumatoid factors are predominantly produced at the earliest stages of rheumatoid arthritis.

Adult↗
PubMed1989

Which antigen to use in the detection of rheumatoid factors? Comparison of patients with rheumatoid arthritis and subjects with 'false positive' rheumatoid factor reactions.

In the search for differences between rheumatoid factors (RF) in patients with rheumatoid arthritis (RA) and in non-rheumatoid subjects, the reactivity of IgM- and IgA-class RF with rabbit IgG (rIgG) and Fc fragments of rabbit and human IgG (rFc, hFc) was studied by enzyme immunoassay. From a community-based cohort (n = 7124) representing the adult population of Finland, RA patients (n = 130), other subjects positive in the Waaler-Rose (WaRo, sensitized sheep cell agglutination) test (n = 137), and controls matched for age, sex and living area were selected for further study. In RA sera there was a good correlation between the results in the WaRo test and in the IgM-RF ELISA (rIgG, rFc and hFc). A considerable number of 'false positive' sera, though positive in the WaRo test and the rIgG-ELISA, were negative in the rFc-ELISA. Twenty-two per cent of the false positive sera reacted with either hFc or rFc, both types being equally common. IgA-RF reacted more frequently with hFc than with rFc in both the RA and the 'false positive' sera. In some sera, IgM- and IgA-RFs reacted differently with human and rabbit Fc, e.g. IgM-RF reacted only with human Fc, and IgA-RF reacted with both hFc and rFc, thus suggesting different regulation of their formation.

Adult↗
PubMed1995

Antimycobacterial hsp65 and rheumatoid factor titres in a population of normal twins: evidence of genetic control of rheumatoid factor.

Rheumatoid arthritis (RA) is an autoimmune disease and rheumatoid factor (RF), anti-IgG, has been implicated in the pathogenesis, but the exact etiology remains unclear. There are data to suggest and infectious trigger to the autoimmune process, and mycobacteria are considered a candidate. Immunization of various animals with mycobacterial heat shock protein 65 (mhsp65) protects against subsequent autoimmune arthritis in a number of experimental models. Elevated anti-mhsp65 titres have been demonstrated in RA patients, together with specific T cells isolated from inflamed synovium. Mycobacterial hsp65 has also been implicated in other autoimmune disease and in atherosclerosis. The anti-mhsp65 and RF (IgG, IgM and IgA isotypes) titres were assayed by ELISA in 123 pairs of normal twins (61 monozygotic and 62 dizygotic, age 14-79 years), to examine the population distribution and inter-relationship of these antibodies. In addition, we studied the effects of age, sex, genetics and environment on antibody titres. IgG-RF and IgM-RF were detectable in all subjects and IgA-RF in 41 subjects. None of the RF isotypes showed any significant dependence on age or sex. There was a statistically significant correlation between twins for the IgG-RF and IgM-RF, and a positive but not significant correlation for the IgA-RF. All three correlations were stronger for monozygotic than dizygotic twins, reaching statistical significance for IgM-RF (P < 0.001), and this indicates that there is a genetic influence on RF titres. Anti-mhsp65 titres were detectable in 90.5% of the study group with a range of 0.15-19.7 AU/ml. There were weak correlations between twins, stronger for dizygotic than monozygotic twins. This suggests that familial influences on anti-mhsp65 titres are very small, with no evidence of any genetic influence at all. There was no significant relationship of anti-mhsp65 titre with age, sex or RF titres.

Adolescent↗
PubMedDate not supplied

7S IgG rheumatoid factor and hidden 19S IgM rheumatoid factor in juvenile chronic arthritis.

Hidden 19S IgM rheumatoid factor (RF) and 7S IgG RF were assayed in 24 children with juvenile chronic arthritis (JCA) and 26 controls, in whole sera and in the IgM and IgG containing fractions of the serum after separation by acid gel filtration. When non-fractioned serum was used, IgM RF detection was positive in 4.2% by latex fixation test and 4.2% by ELISA. IgG RF was positive in 91.7% by ELISA. In the IgM containing fraction of the serum, the positivity for IgM RF was 41.7% by LFT and 54.2% by ELISA. In the IgG containing fraction the positivity for IgG RF was 100%. These results suggest toward the need of previous serum dissociation before hidden 19S IgM RF is assayed and demonstrate high prevalence of 7S IgG RF.

Adolescent↗
PubMed1989

Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, and hidden rheumatoid factors.

The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs.

Adult↗
PubMedDate not supplied

IgG-rheumatoid factor in a population of elderly males: relationship to IgM-rheumatoid factor and rheumatoid arthritis.

The occurrence of IgG-rheumatoid factor (RF) reacting with rabbit IgG was studied in the sera of 1,105 elderly males from rural areas of Finland. Elevated levels of IgG-RF were found in 12 sera, 11 of which contained also IgM-RF, as measured by conventional agglutination tests and/or by enzyme-linked immunosorbent assay. Subjects with rheumatoid arthritis and those with "false" positive RF reactions did not differ from each other with respect to the occurrence of IgG-RF.

Adult↗
PubMed1993

Allotypic dependency of the specificity and avidity of human monoclonal IgM rheumatoid factors derived from rheumatoid synovial cells.

OBJECTIVE: To better understand the genetic derivation and pathogenicity of rheumatoid factor (RF) molecules in rheumatoid arthritis (RA), we have focused our studies on rheumatoid synovial cells (RSC). METHODS: Five monoclonal human IgM rheumatoid factor (mRF)-secreting hybridomas were produced from the RSC of an RA patient. Fine subclass specificities and avidities of these RSC mRFs were compared with several paraprotein monoclonal IgM RFs using direct binding (reactivity) and competitive inhibition (specificity and avidity) enzyme-linked immunosorbent assays. RESULTS: The following observations were made: 1) RSC mRF had greater avidity for IgG than did paraprotein mRF; 2) 4 of the 5 RSC RF were highly avid for IgG3; and, 3) the avidity of RSC RF binding for IgG3 was highest for IgG molecules expressing the G3m(5) allotype. CONCLUSION: We conclude that RSC RF have different specificities and avidities than do paraprotein RF. This may suggest an antigen-driven process in RA synovium, with the production of higher-avidity IgG3m(5)-specific RSC RF, which could have special pathogenetic importance.

Adult↗
PubMed1977

[Prognostic significance of serum iron level, hemoglobin and rheumatoid factor titre in rheumatoid arthritis].

On the basis of the results of a five-year examination of the course on 120 patients with rheumatoid arthritis the authors adopt a definite attitude to the prognostic significance of hypersiderinaemia, anaemia and height of the titre of the rheumatoid factor. With the help of the chi2-test and the rank correlation after Spearman the statistical relations to stage, activity, clinical and radiological progressing as well as to the number of the affected joints were examined. In seropositive patients we found a correlation of the titre of rheumatoid factor and stage. Furthermore a clear correlation existed to clinical and radiological progressing as well as to the number of the affected joints. Early highly positive titres of the rheumatoid factor as an expression of high immunologic activity suggest an unfavourable prognosis in the majority of cases. Constant anaemia and hyposiderinaemia as symptoms of a high basis activity of the disease also showed close relations to the progressing. From this result indications for the early use of important therapeutic measures. For the prognostic judgement of the course of the disease of rheumatoid arthritis it is necessary to have at disposal further methodically simply determinable parameters for the recognition of the basis activity and the immunologic activity.

Anemia, Hypochromic↗
PubMed1988

Fc epitopes for human rheumatoid factors and the relationships of rheumatoid factors to the Fc binding proteins of microorganisms.

Work from our laboratories has shown that the major antigenic determinants for rheumatoid factors (RFs) are in the C gamma 2-C gamma 3 interface region of IgG in the same area that binds staphylococcal protein A (SPA). Furthermore, the Fc binding proteins of groups A, C and G streptococci as well as the Fc binding proteins induced on cell surfaces by herpes simplex virus type I also bind to the same area of IgG. These binding site similarities between RFs and the microbial Fc binding proteins suggested conformational similarities between the RF antigen combining regions and the Fc binding regions of the microbial proteins. This hypothesis was supported by the observation that antibodies to SPA bind to the antigen combining regions of most RFs as well as to the Fc binding region of the T15 group A streptococcal Fc binding protein. These findings indicate that RFs bear the conformational internal image of these microbial proteins and suggest that RFs could arise as antibodies to the idiotypic determinants on antibodies to microbial Fc binding proteins. Alternatively, microbial Fc binding proteins could present IgG to the immune system in a way that renders specific areas of the C gamma 2-C gamma 3 interface region immunogenic. These relationships between RFs and microbial Fc binding proteins may prove to be important for our understanding of the generation of RFs in rheumatoid arthritis.

Binding Sites↗
PubMed1986

Studies on rheumatoid factor: I. The effect of rheumatoid factor on the clearance of preformed immune complexes in mice.

The blood clearance of passively transferred immune complexes (IC), preformed at different antigen-antibody ratios, was measured in mice with LPS-induced rheumatoid factor (RF) and in normal controls. RF had a differential effect on IC clearance, significantly enhancing clearance of complexes formed in antibody excess and slight antigen excess but inhibiting the clearance of complexes formed in moderate (x10) antigen excess. The results are discussed with regard to the mechanisms of IC clearance and suggest that RF may play an important role in governing the behaviour of immune complexes in vivo.

Animals↗
PubMed1983

Symposium on the immunodiagnosis of rheumatic and related diseases, Part II. Rheumatoid factors.

Human rheumatoid factors are antibodies of IgG, IgA, or IgM class that show reactions with antigenic determinants present on other immunoglobulin molecules. The most commonly measured rheumatoid factor relates to the 19S IgM type, which reacts by agglutination of latex particles coated with 7S IgG and is often measured in the standard latex fixation test. Approximately 65 to 70 per cent of patients with rheumatoid arthritis show positive serologic tests for rheumatoid factor; however, a number of other chronic disease conditions are also associated with positive rheumatoid factor reactions, including infective endocarditis, sarcoidosis, leprosy, and other hyperglobulinemic conditions. Although extensive serologic and immunochemical studies have identified a number of specific antigenic structural sites on immunoglobulin molecules that react with rheumatoid factors, recent studies have shown that a certain proportion of such antibodies may show cross-reactivity with DNA-histone complexes as well. It is still not entirely clear how rheumatoid factors fit into the pathogenesis of rheumatoid arthritis itself.

Aging↗
PubMed1990

Suppression of rheumatoid factor production by methotrexate in patients with rheumatoid arthritis. Evidence for differential influences of therapy and clinical status on IgM and IgA rheumatoid factor expression.

Suppression of rheumatoid factor (RF) production in rheumatoid arthritis (RA) has been variably attributed to the use of remittive agents per se or to clinical improvement associated with their use. There have been conflicting reports with regard to the influence of methotrexate (MTX) on serum RF levels in RA. We determined IgM-RF and IgA-RF levels in paired serum samples (obtained at study entry and completion) from RA patients enrolled in multicenter trials with the Cooperative Systematic Studies of Rheumatic Diseases program. After exclusion of the 14 IgM-RF-negative sera, there were samples from 30 MTX-treated patients and 52 placebo-treated patients. Changes in IgM-RF and IgA-RF levels were weakly associated with each other. Significant decreases in IgM-RF levels were observed in the MTX-treated patients, but not in the placebo group. These changes were most significant in the MTX-treated patients who improved clinically. There were significant decreases in IgA-RF levels at study completion among MTX-treated patients who had improved clinically and those who had not improved clinically, but not in the placebo group. The contributions of clinical improvement and MTX treatment to changes in serum IgM-RF and IgA-RF levels were examined using a logistic regression model. Changes in IgM-RF were strongly related to MTX treatment and, to a lesser extent, to clinical improvement; changes in IgA-RF were related only to MTX treatment. These results indicate that MTX treatment per se decreases both IgM-RF and IgA-RF levels, whereas clinical improvement correlates with decreased IgM-RF levels only.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1993

Human rheumatoid factor cross-idiotypes. IV. Studies on WA XId-positive IgM without rheumatoid factor activity provide evidence that the WA XId is not unique to rheumatoid factors and is distinct from the 17.109 and G6 XIds.

The WA cross-idiotype (XId) is the major XId among human monoclonal rheumatoid factors (mRF) and is almost always associated with the light (L) chain XId, 17.109, and the heavy (H) chain XId, G6. A cell line, 35G6, was cloned that bears the WA XId, but shows no reactivity with immunoglobulin G (IgG) and is negative for the 17.109 and G6 XIds. The 35G6 L chain appears to be derived from the same VKIII-JKI genes as most WA mRFs L chains. In contrast to the WA mRFs H chains in which VH1 genes are used, the 35G6 IgM expresses a VH3 gene. Sequence comparisons with other WA XId-positive mRF suggested several common structural features that may be related to the WA XId and differences that may relate to lack of IgG reactivity. Cells similar to 35G6 have previously been described in pokeweed mitogen-stimulated cell lines of peripheral blood lymphocytes from normal individuals and patients with rheumatoid arthritis and type II mixed cryoglobulinemia. These observations were confirmed, and in addition, it was shown that the majority of WA XId-positive cells in these cultures were negative for the 17.109 and G6 XIds. The presence of the WA XId in the absence of IgG reactivity suggests that the WA XId is more directly associated with an antigen specificity other than IgG, and its association with RF activity may be incidental. It is postulated that these WA XId-positive RF-negative antibodies may serve a physiologic role as natural antibodies to a pervasive pathogen, and that IgG reactivity is a consequence of somatic diversification accompanying proliferation of the WA XId-positive RF-negative cell.

Amino Acid Sequence↗
PubMedDate not supplied

Relative reactivities of rheumatoid factors in serum and cells. Evidence for a selective deficiency in serum rheumatoid factor.

Investigations of rheumatoid factors by a hemolytic plaque forming cell assay of blood lymphocytes with sensitized sheep cells have suggested that the rheumatoid factors released from the cells have higher affinities for human IgG than do the rheumatoid factors measured in the patient's serum. This study reaffirms this observation and provides evidence that the reported differences are not artifacts of technique. The findings imply that rheumatoid factors of higher affinity for IgG than those of the serum are being released into the tissue fluids by lymphocytes and locally precipitated. Such rheumatoid factors may never reach the peripheral blood serum in detectable quantity or may do so only infrequently.

Animals↗
PubMed1993

[Experimental method and clinical significance of hidden rheumatoid factors].

Hidden rheumatoid factor (HRF) was detected in rheumatoid arthritis (RA) serum with ELISA after separation and dissociation of immune complex (IC). It was found that 60% of the patients with active RA has positive latex fixation test, whereas 96% of them has been demonstrated to have IgM hidden rheumatoid factor (HIgMRF) and 70% of them IgG hidden rheumatoid factor (HIgGRF). When the disease was controlled, HIgMRF and HIgGRF was found in 24% and 12% respectively. The difference was significant with P < 0.01. Our results show that the presence of HRF in RA patients is related with the activity of the disease, but not with duration of disease, sex and age.

Adult↗
PubMed1990

Serologic and molecular characterization of a human monoclonal rheumatoid factor derived from rheumatoid synovial cells.

Molecular characterization of rheumatoid factors (RF) in rheumatoid arthritis (RA) has been hampered because of their polyclonality. To overcome this problem, we generated monoclonal RF-secreting hybridomas from rheumatoid synovial cells. Among the RF-secreting hybridomas, HAF10 secreted an IgM-RF that was monospecific for human IgG. It bound well to IgG1 and IgG2, but not to IgG3 and IgG4. Sequence analysis of its heavy and light chains showed that it contained a VH1 heavy chain and a V lambda light chain that did not belong to any known lambda light chain subgroup, and therefore, probably represented a new lambda subgroup. These results indicated that both the heavy and light chains of a monoclonal IgM-RF from rheumatoid synovial cells were quite different from the reported variable region sequences of several monoclonal RF derived mainly from patients with mixed cryoglobulinemia. Further studies of additional monoclonal RF from RA patients are warranted to define precisely their genetic basis and to further our understanding of the immunopathology of RA.

Amino Acid Sequence↗
PubMed1992

Generation and characterization of two monoclonal self-associating IgG rheumatoid factors from a rheumatoid synovium.

OBJECTIVE: To study IgG rheumatoid factor (RF) from rheumatoid synovium. METHODS: We fused the K6H6/B5 human-mouse heterohybridoma with unstimulated rheumatoid synovial B cells to generate IgG-RF-secreting hybridomas. RESULTS: The RFs from 2 such hybridomas bound specifically to the Fc fragment of human IgG and self-associated to form immune complexes. Such immune complexes are a major characteristic of the pathogenic IgG-RFs in rheumatoid synovium. CONCLUSION: IgG-RF-secreting hybridomas have been obtained. Analyses may reveal the underlying mechanisms of the induction of IgG-RF.

Animals↗