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[Preponderant synthesis of rheumatoid factors by synovial plasma cells in rheumatoid polyarthritis].

Plasma cells synthesising rheumatoid factor have been identified by immunofluorescent studies of sections of cells eluted from synovial membranes poor in macrophages. More than 90% of the IgM plasma cells produce rheumatoid factor, while 50 to 60% of IgG plasma cells and only 10% of IgA plasma cells produce rheumatoid factor. The equivalent results obtained in patients with sero-positive and sero-negative rheumatoid arthritis suggest that auto-immunisation between the IgG plays the same determinant role in the pathophysiology of the two types of rheumatoid arthritis.

Arthritis, Rheumatoid↗

IgG rheumatoid factor in dental periapical lesions of patients with rheumatoid disease.

To detect "hidden" IgG rheumatoid factor in tissues from dental periapical lesions, 26 rheumatoid and 14 control patients were examined by the direct immunofluorescence technique for binding of FITC-labelled IgG before and after pepsin digestion. Whereas free rheumatoid factor was detected in only 1 rheumatoid tissue before digestion with pepsin, this tissue as well as 8 other rheumatoid tissues strongly bound heat-aggregated IgG after the digestion procedure. Six of these 9 tissues also bound native IgG. In no control tissue was free rheumatoid factor detected and in only 1 was "hidden" rheumatoid factor revealed after pepsin digestion. Hence, presence of IgG rheumatoid factor correlated positively with the presence of rheumatoid disease, and evidence was established that certain features of rheumatoid inflammation occur in dental periapical lesions of many patients with rheumatoid disease.

Adult↗

A population study of rheumatoid factor in Iceland. A 5-year follow-up of 50 women with rheumatoid factor (RF).

The subject of this paper is a 5-year follow-up of 50 women found with Rose-Waaler Titre greater than or equal 1 : 10 or with a Acryl Fixation Titre greater than or equal 1 : 10 in a general health survey conducted in the Reykjavik area in 1968-1969. The average annual incidence of RA was 2.3 percent. Of four women who died during the follow-up period, three were amongst those with the highest titres. Two of the decreased had cancer mammae and one had lung cancer. Changes in RF-titres and New York Criteria are also discussed. It is suggested that RF-positives could be divided in three different riskgroups.

Adult↗

Specificity of rheumatoid factors in relation to the disease state in rheumatoid arthritis.

Rheumatoid factors found in patients with rheumatoid arthritis react with human IgG and with IgG from some other species. The levels of rheumatoid factor give some indication of prognosis, albeit a rather poor one in this highly variable disease. The high degree of variability may, in part, be due to differences in the fine specificity of the rheumatoid factor in each individual patient, leading to differences in the types of immune complex formed. To study this hypothesis the fine specificity of rheumatoid factors of the IgM, IgA, and IgG classes for IgG from human, baboon, orangutan, macaque, owl monkey, gorilla, marmoset, cow, pig, sheep, goat, horse, mouse, and chicken was examined. Differential reactivity for these species was found and associations between the presence of rheumatoid factor and the development of moderate or severe erosions.

Animals↗

The mucin clot test and the synovial fluid rheumatoid factor as diagnostic criteria in rheumatoid arthritis.

We evaluated the diagnostic usefulness of 2 synovial fluid (SF) tests viz the mucin clot test (MCT) and the rheumatoid factor (RF) test in rheumatoid arthritis (RA). SF was obtained from 140 patients, 60 with RA, 80 with other articular diseases. The sensitivity and specificity of the MCT in RA were 76% and 49%, respectively; the positive and negative predictive values (PPV, NPV) were 52% and 73%. The sensitivity and specificity of SF RF were 63% and 91% respectively compared with corresponding values of 75% and 87% for serum RF; PPV and NPV were 89% and 69%, and differed little from values obtained for serum RF. Our results suggest that RA diagnostic criteria should be revised to exclude the MCT, and that the detection of RF in SF in addition to its determination in serum is unnecessary in establishing a diagnosis of RA.

Adolescent↗

Hidden rheumatoid factor and Wa idiotype expression in juvenile rheumatoid arthritis.

The major rheumatoid factor cross-reactive idiotype, which was defined by prototypic monoclonal IgM rheumatoid factors from Waldenstrom's macroglobulinaemia patient Wa, is present on 60% of all monoclonal IgM RF paraproteins. One-third of patients with juvenile rheumatoid arthritis (JRA), who are seronegative for classic IgM rheumatoid factor (RF), express the Wa idiotype in high titre in their sera. To determine if the Wa idiotype is present on hidden rheumatoid factors in JRA patient sera, we studied hidden RF expression by both ELISA and haemolytic assay techniques. The majority of JRA sera with increased concentrations of the Wa idiotype did not have increased RF activity nor hidden RF activity. In some JRA patients, the Wa idiotype may be expressed on a parallel set of immunoglobulin molecules, related to RFs, but lacking the ability to bind to IgG.

Adolescent↗

[Immunohistochemical detection of tissue-bound rheumatoid factors (author's transl)].

Different immunoglobulin classes, complement factors, complement fixation and rheumatoid-factor activity in rheumatoid synovial membranes of 16 patients were studied. After pepsin digestion of tissue sections, greatly increased numbers of plasma cells were able to bind human gamma globulin. In addition we found after the pepsin digestion more IgG and less IgM in the tissues. The results gave evidence of intracellular blocking of rheumatoid factor activity, due to IgG-IgG rheumatoid factor complexes or self associated rheumatoid factors. Additional evidence of such plasma cell complexes was obtained by observing an in vitro fixation of the complement. With the same methods we studied 3 patients whose synovial membranes had been surgically removed not later than 6 months after the onset of evident symptoms and who developed rheumatoid arthritis within an observation period of 2 years. As a result we found a small production of predominantly M and G immunoglobulins. The rheumatoid factors were also found in a small degree. Rheumatoid factor activity can be revealed only in a little number of plasma cells by pepsin digestion of tissues. In the serum we can't find more rheumatoid factor activity after pepsin digestion in the latex test. The immunofluorescence for detection of rheumatoid factors in tissues is a practicable method and important for the differential diagnosis of joint diseases.

Arthritis, Rheumatoid↗

Complement-fixing hidden rheumatoid factor in children with benign rheumatoid nodules.

Rheumatoid nodules have been described in many children without evidence of clinical disease. These have been referred to as benign rheumatoid nodules (BRN). Except for one report, no serological abnormalities have been demonstrated. Four children with BRN have been studied. By means of a hemolytic assay, high titers of hidden rheumatoid factor (RF) have been found in the blood, i.e., 19S IgM RF detected after acid separation of IgM-containing fraction from the serum. The median hidden RF titer of the children with BRN was 1:362 and in healthy and disease controls was 1:7. The difference was significant at P less than 0.001. The results indicate that patients with BRN have active complement-fixing 19S IgM RF in their serum. Thus the association of hidden RF with BRN raises the possibility that the deposition of immune complexes (19S IgM-7S IgG) leads to small vessel vasculitis and nodular formation.

Antigen-Antibody Complex↗

The roles of IgG, IgM rheumatoid factor, and their complexes in the induction of polymorphonuclear leukocyte chemotactic factor from complement.

The induction of chemotactic factor by rheumatoid factor (RF) and by rheumatoid complexes and their constituents was investigated. The presence of chemotactic factor was measured by the number of polymorphonuclear leukocytes (obtained from normal individuals) attracted through a 3 mum Millipore filter and is expressed as a "chemotactic index." The chemotactic index was used to measure the effect of immunoglobulins and their complexes in stimulating production of complement-derived chemotactic factors from the sera of normal individuals. Two sources of IgG (F-II and DEAE-purified IgG) were used. These were prepared for use in the native and heat-aggregated states. The same chemotactic index was obtained with both these preparations of IgG. The chemotactic index increases when (a) increasing concentrations of gamma globulin were added to a constant concentration of complement and (b) when the amount of complement alone was increased. The addition of a purified IgM RF to the mixture of IgG and complement caused a decrease in the chemotactic index. Incubation of IgG and complement before addition of IgM RF produced no change in the chemotactic index. The addition of a nonrheumatoid factor IgM to IgM and complement had no effect on the chemotactic index. IgM RF and IgG alone were not chemotactic. These studies confirm the concept of "complement deviation" by IgM RF which occurs with, and as a result of, the immune complex formation between IgG and IgM RF. The successful activation of complement chemotactic factors by IgG may explain the synovitis with high polymorphonuclear leukocyte counts found in RF-negative arthritis.

Antigen-Antibody Complex↗

Does rheumatoid factor always mean arthritis?

Rheumatoid arthritis is a clinical syndrome, and the diagnosis requires the presence of pain, swelling, and tenderness in the joints. In the absence of these features, identification of rheumatoid factor in the serum is of little use. Because rheumatoid factor is an immune complex, it is a marker of immune activation and, therefore, may be present in the circulation of persons with a variety of inflammatory conditions that stimulate the immune system. Also, 5% of the healthy population have significant titers of rheumatoid factor in their serum.

Age Factors↗

Rheumatoid factors in the pathogenesis of rheumatoid arthritis.

Rheumatoid factors (RF) participate in the pathogenesis of rheumatoid arthritis by formation of immune complexes. IgM-RF form complement activating immune complexes with IgG-containing antigen-antibody complexes. IgG-RF form unique immune complexes without the presence of separate antigen molecules. The specificities of RF in rheumatoid arthritis have subtle differences from RF formed by B cell neoplasms. Immune deposits in rheumatoid articular cartilage have high potential for generating inflammation and contain RF. The immune deposits in articular cartilage need to be characterized further, and the mechanisms that initiate and perpetuate RF production in patients with rheumatoid arthritis should be elucidated.

Antigen-Antibody Complex↗

Association of rheumatoid factor with complement activation in rheumatoid arthritis and other diseases.

Rheumatoid factor (RF) is a complement activating autoantibody. In rheumatoid arthritis (RA) the rate of catabolism of complement is closely related to the titre of RF. Therefore, we have examined whether these relationships are unique to RA or will be found in non-RA disorders in which RF may be found in the circulation. We studied patients with subacute bacterial endocarditis, leprosy, tuberculosis, and a variety of other rheumatic and vasculitic disorders. We found that in all the disorders examined the RF had a complement activating potential which was equivalent to that of the RF of RA patients. Furthermore in vivo activation of complement, as exhibited by the appearance of C3 degradation products, was significantly related to higher titres of haemolytically active RF in non-RA as well as the RA group. In these respects, therefore, the RF in RA and non-RA patients is indistinguishable. A possible survival value for RF is discussed.

Adolescent↗

Generation and molecular characterisation of monoclonal IgG4 rheumatoid factor from a patient with rheumatoid arthritis.

OBJECTIVE: To characterise IgG4 rheumatoid factor (RF) at the molecular level from a patient with rheumatoid arthritis. METHODS: B cells were cloned from the peripheral blood of a patient with rheumatoid arthritis, using EB virus transformation. The supernatants of the clones were screened for IgG RF activity by ELISA. Nucleotide sequences of the expressed immunoglobulin heavy and light chain genes of one IgG RF producing clone were determined by direct sequencing of the products of a polymerase chain reaction. RESULTS: One clone producing monospecific IgG4 RF was obtained. Sequence analysis of the heavy and light chain genes suggested the accumulation of somatic mutations resulting in amino acid replacement in complementarity determining regions. CONCLUSIONS: The results may suggest an antigen driven response in the generation of IgG4 RF in rheumatoid arthritis disease processes.

Amino Acid Sequence↗

Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis.

BACKGROUND: Recent epidemiological studies have suggested that smoking is a risk factor for rheumatoid factor (RF) positive rheumatoid arthritis (RA). Being overweight, high serum cholesterol, and dietary factors have in some studies been found to be associated with the risk of RA. No attention, however, has been paid to coffee consumption as a risk determinant, though it is a shared covariate of the alleged risk factors. OBJECTIVES: This study aimed at examining coffee consumption for its associations with RF positivity and with the risk of RA. METHODS: Coffee consumption was studied, firstly, for its association with RF (sensitised sheep cell agglutination titre >/=128) in a cross sectional survey of 6809 subjects with no clinical arthritis, and secondly, for its prediction of RA in a cohort of 18 981 men and women who had neither arthritis nor a history of it at the baseline examination in 1973-76. Up to late 1989, 126 subjects of the cohort study had developed RA, of whom, 89 were positive for RF by the time of diagnosis. RESULTS: In the cross sectional survey the number of cups of coffee drunk daily was directly proportional to the prevalence of RF positivity. Adjusted for age and sex this association was significant (p value for linear trend, 0.008), but after further adjustment for smoking the linear trend declined below significance (p=0.06). In the cohort study there was an association between coffee consumption and the risk of RF positive RA that was not due to age, sex, level of education, smoking, alcohol intake, body mass index, or serum cholesterol. After adjustment for these potential confounders the users of four or more cups a day still had a relative risk of 2.20 (95% confidence interval 1.13 to 4.27) for developing RF positive RA compared with those drinking less. Coffee consumption did not predict the development of RF negative RA. CONCLUSION: Coffee consumption may be a risk factor for RA, possibly through mechanisms contributing to the production of RF. This hypothesis remains to be tested in further studies.

Adult↗

Demonstration of anti-idiotypic antibodies directed against IgM rheumatoid factor in the serum of rheumatoid arthritis patients.

We have identified the presence of anti-idiotypic activity against IgMRF in the sera of RA patients. Only patients seropositive for IgMRF had significant levels of anti-idiotypic activity, while seronegative patients and normal volunteers did not. When this anti-idiotypic activity was affinity-purified from a single RA patient, two separate binding activities were identified. IgG antibodies were pepsin-digested to F(ab')2 fragments before affinity-purification to remove the Fc portion capable of binding to IgMRF. Anti-idiotypic F(ab')2 fragments of IgG were eluted from an IgMRF-Sepharose 4B column. These F(ab')2 bound preferentially to IgMRF bearing an idiotype recognized by the anti-idiotypic murine monoclonal 17.109. A second anti-idiotypic F(ab')2 was affinity purified using rabbit anti-human Fc antibody bound to Sepharose 4B. These eluted antibodies behaved as the internal image of IgG, binding five out of seven IgMRF's tested. The binding of both anti-idiotypic F(ab')2 was inhibited with human IgG. The presence of both IgMRF and anti-idiotypic antibodies directed against it in the sera of RA patients suggests that anti-idiotypic antibodies alone are not capable of inhibiting the production of rheumatoid factor.

Arthritis, Rheumatoid↗

IgE rheumatoid factor in a case of rheumatoid arthritis with pleuritis.

IgE rheumatoid factor (RF) was detected in sera from 4 out of approximately 100 rheumatoid patients using a solid phase enzyme-linked immunosorbent assay. All 4 patients had extraarticular lesions. A quantitative analysis revealed that over 60% of total IgE in the serum and pleural fluid from a rheumatoid patient with pleuritis had RF activity. The changes in the level of serum IgE RF in our case paralleled the disease activity. This study suggests that IgE RF may play some role in the pathogenesis of certain extraarticular features of RA.

Absorption↗