Conjugal prevalence of rheumatoid arthritis, rheumatoid factor and other autoantibodies in rheumatoid arthritis.
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Adult↗
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[Standardization of the latex fixation test for the demonstration of the rheumatoid factor. 3. Nature of the rheumatoid factor in normal serum, in serum of patients with rheumatoid arthritis, and in serum of the aged].
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Aged↗
Most African-American patients with rheumatoid arthritis do not have the rheumatoid antigenic determinant (epitope)
OBJECTIVE: To evaluate the relation between the presence of the "rheumatoid epitope," defined by a sequence motif in the HLA-DRB1 alleles, and disease severity in African-American patients with rheumatoid arthritis. DESIGN: Cross-sectional study. SETTING: Rheumatology outpatient clinics at two university medical centers. PATIENTS: 86 African-American patients with rheumatoid arthritis (66 seropositive and 20 seronegative for the rheumatoid factor) attending the clinics and 88 healthy African-American persons. MEASUREMENTS: HLA-DRB1 alleles were determined by restriction fragment length polymorphism and by allele-specific oligonucleotide typing of polymerase chain reaction-amplified HLA-DRB1 second exons. RESULTS: With the exception of an increased frequency of HLA-DRB1*04 alleles in seropositive patients with rheumatoid arthritis (27.3%) compared with controls (13.1%) (P = 0.02), the frequencies of HLA-DRB1 alleles were similar in patients and controls. Most seropositive (48 of 66) and seronegative (15 of 20) patients were HLA-DR4 negative, but some (7 of 48 seropositive patients and 3 of 15 seronegative persons) inherited the rheumatoid epitope on a non-DR4 allele. Disease features, including severity, were similar for patients without the epitope and for those with either a single or a double dose of an epitope-positive allele. Positivity for rheumatoid factor, but not for the rheumatoid epitope, was weakly associated with severity in these patients. CONCLUSION: Most African-American patients with rheumatoid arthritis did not express the rheumatoid epitope. The predisposition to and severity of rheumatoid arthritis in African-Americans appears to be independent of the presence and dose of the shared rheumatoid epitope.
Adult↗
Smoking is a strong risk factor for rheumatoid nodules in early rheumatoid arthritis.
OBJECTIVE: To examine whether smoking is a risk factor for rheumatoid nodules in early rheumatoid arthritis, and if so to determine the quantitative effect of smoking. METHODS: From a cohort (n = 1589) in a structured programme for follow up of newly diagnosed cases of rheumatoid arthritis (symptoms of swollen joints < or =12 months), 112 individuals with rheumatoid nodules at inclusion were identified. Nodular patients were each compared with two age and sex matched controls without nodules from the same cohort. A detailed self administered tobacco use questionnaire was answered by 210 patients (63%). RESULTS: Seventy patients were current smokers, 71 former smokers, and 69 had never smoked. Current smoking and former smoking were more common in patients with rheumatoid nodules compared with controls (86% v 59%) in both sexes. Positive rheumatoid factor (RF) was found more often among cases with nodules than controls (78% v 64%). Using detailed information from the questionnaires with conditional logistic regression analyses, ever having smoked was associated with an increased risk of the presence of rheumatoid nodules (odds ratio (OR) = 7.3 (95% confidence interval, 2.3 to 23.6); p = 0.001). The risk of having nodules was not obviously dose dependent when smoking duration as well as smoking amount were examined. A stratified analysis showed that only RF positive smokers had an increased risk of rheumatoid nodules. Smoking was associated with rheumatoid nodules among both men (p = 0.006) and women (p = 0.001). Tobacco use other than smoking (n = 31) was not associated with an increased risk of nodules (OR = 0.8 (0.2 to 3.4); p = 0.813). CONCLUSIONS: There is a strong association between smoking and rheumatoid nodules in early seropositive rheumatoid arthritis.
Adult↗
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↗
Free rheumatoid factor in dental periapical lesions and gingivae of patients with rheumatoid disease.
To determine whether evidence of rheumatoid inflammation, in the form of free rheumatoid factor, might be found in the teeth-supporting tissues of patients with known rheumatoid disease, tissues from the dental periapical lesions of one group of 50 rheumatoid and 23 control patients, and from the marginal gingivae of a second group of 58 rheumatoid patients were examined by the direct immunofluorescence technique that employed fluroesceinisothiocyanate (FITC)-labelled aggregated human IgG. The gingival tissues contained no free rheumatoid factor. Free rheumatoid factor-producing plasma cells were, however, detected in the dental periapical lesions of 3 of the 50 rheumatoid patients, i.e. in 6%, and in 1 of the control patients i.e., in 4%. This control patient had suffered from nephritis 10 months prior to the investigation. Because free rheumatoid factor did occur, albeit infrequently, in the dental periapical lesions of rheumatoid patients, a search for IgG rheumatoid factor, known to occur in greater abundance than the IgM type although "hidden", was indicated.
Adult↗
Rheumatoid nodules located in the penis of a methotrexate-treated patient with rheumatoid arthritis.
A case is reported in which a patient with a rheumatoid factor-negative rheumatoid arthritis developed rheumatoid nodules in the penis during treatment with methotrexate. The development of rheumatoid nodules in seronegative rheumatoid arthritis patients is extremely rare. An acceleration of rheumatoid nodules in methotrexate-treated rheumatoid arthritis patients is reported in literature. Regarding the case reported here, we propose a causal relationship between methotrexate-treatment and the development of rheumatoid nodules in our patient. Methotrexate should not be the preferential treatment for patients with rheumatoid arthritis developing rheumatoid nodules and suffering from vasculitis.
Arthritis, Rheumatoid↗
Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis.
OBJECTIVE: To study antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor in patients with active, severe extra-articular rheumatoid arthritis (ExRA) compared with controls without ExRA. METHODS: 35 consecutive patients with severe ExRA manifestations according to predefined criteria were studied. 70 patients with rheumatoid arthritis, but no ExRA manifestations, individually matched for age, sex and disease duration, served as controls. Patients were included when ExRA was diagnosed, before any new treatment was started. Anti-CCPs were detected with ELISA, rheumatoid factor was quantified using nephelometry and anti-nuclear antibodies (ANA) were investigated using indirect immune fluorescence. RESULTS: Anti-CCPs were detected in 77% of patients with ExRA versus 56% of controls without ExRA (p = 0.03). Anti-CCP levels also tended to be higher in patients with ExRA (p = 0.09). Rheumatoid factor was detected in 94% v 71% of patients and controls, respectively (p = 0.006), and rheumatoid factor levels were higher in patients with ExRA (median interquartile range (IQR) 245 IU/ml (94-604) v 73 IU/ml (not detected-165); p = 0.001). Levels and occurrence of ANA did not differ between patients with ExRA and controls. Patients with ExRA had higher swollen joint counts and C reactive protein levels, but no correlations were found between anti-CCP or rheumatoid factor levels and these measures within the ExRA group. CONCLUSION: Rheumatoid factor is strongly associated with severe ExRA manifestations in patients with rheumatoid arthritis, and a similar but weaker association exists for anti-CCPs. This suggests a role for rheumatoid factor and anti-CCP in the pathogenesis of ExRA.
Acute Disease↗
Rheumatoid factor seropositivity is inversely associated with oral contraceptive use in women without rheumatoid arthritis.
OBJECTIVES: To examine whether oral contraceptive use is associated with the presence of serum rheumatoid factor in women of reproductive age without rheumatoid arthritis. METHODS: 304 women selected from parents of children who were at increased risk of developing type 1 diabetes were studied, because they were enriched with the human leucocyte antigen-DR4 allele, a susceptibility marker for both type 1 diabetes and rheumatoid arthritis. Participants visited a clinic where blood was drawn for rheumatoid factor testing, and exposure data were collected via questionnaires. A medical history and joint examination were performed to rule out rheumatoid arthritis. Participants and examiners were unaware of the participants' rheumatoid factor status at the time of examination and questionnaire. RESULTS: Use of oral contraceptives at any time was inversely associated with rheumatoid factor positivity (adjusted odds ratio (OR) 0.2, 95% confidence interval (CI) 0.07 to 0.52) independent of age, education and smoking. Smoking > or = 20 pack-years was also associated with rheumatoid factor positivity (adjusted OR 56.38, 95% CI 4.31 to 736.98) compared with never smoking. Smoking 1-19 pack-years was not associated with a positive rheumatoid factor. CONCLUSIONS: Our results suggest that oral contraceptive use, and possibly cigarette smoking, act early in the development of the immune dysregulation that occurs in rheumatoid arthritis.
Adult↗
Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis.
OBJECTIVE: To determine the diagnostic and prognostic test qualities of the enzyme linked immunosorbent assays (ELISA) for rheumatoid factor isotypes in rheumatoid arthritis (RA), and to compare them with the latex fixation test. METHODS: Rheumatoid factor tests were performed in 1988 consecutive new rheumatology outpatients within two months after their first visit to the outpatient clinic of the Department of Rheumatology of Leiden University hospital. The sensitivity, specificity, accuracy, and predictive values of the tests in discriminating RA from non-rheumatoid arthritis and erosive from non-erosive disease after two years of follow up were determined and presented as receiver operating characteristic curves and post-test probability curves. RESULTS: The sensitivity of the ELISA for IgG, IgA, and IgM rheumatoid factor for RA versus all controls at optimal cut off titres was 72%, 44%, and 69%, respectively; the specificity was 52%, 84%, and 86%. For the latex fixation test the sensitivity was 66% and the specificity 91%. The post-test probability of RA, at a clinical prevalence rate of 12%, given a positive test result in the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, was 17%, 27%, 40%, and 49%, respectively; with negative test results the probability was 7%, 8%, 5%, and 5%, respectively. The specificity of all tests in discriminating erosive from non-erosive RA at two years was low: 41%, 44%, 47%, and 58% for the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, respectively. CONCLUSION: The ELISAs for IgG and IgA rheumatoid factor are of no significance in diagnosing RA and in the prediction of erosive disease. The ELISA for IgM rheumatoid factor is a reasonable alternative for the latex fixation test when age and gender are taken in to consideration. The specificity of all rheumatoid factor tests in discriminating erosive from non-erosive RA is low.
Adolescent↗
Relationship of rheumatoid factor isotype levels with joint lesions detected by magnetic resonance imaging in early rheumatoid arthritis.
OBJECTIVE: To evaluate the relationship between rheumatoid factor isotypes and articular damage detected by magnetic resonance imaging and plain radiography in early rheumatoid arthritis. METHODS: 20 consecutive patients with early active rheumatoid arthritis underwent determinations of serum IgM, IgA, and IgG rheumatoid factors by enzyme-linked immunosorbent assay (ELISA). Plain radiographs of the hands and wrists were obtained, and the wrist, metacarpophalangeal joints, and proximal interphalangeal (PIP) joints on the more severely affected side were investigated by magnetic resonance imaging before and after gadolinium-DTPA injection. RESULTS: IgM, IgA, and IgG rheumatoid factors were found in 13 (65%), 13 (65%), and 15 (75%) of patients, respectively. Sera from five patients (25%) contained no detectable rheumatoid factor isotypes. Correlations were found among the levels of the three rheumatoid factor isotypes. Levels of IgA, IgG, and IgM rheumatoid factor were significantly higher in patients with than without erosions on magnetic resonance imaging scans. No such difference was found when patients with and without erosions on plain radiographs were compared. Magnetic resonance imaging detected soft tissue lesions more frequently than plain radiography. Magnetic resonance imaging was also more likely than plain radiography to show bone erosions and bone cysts, but this difference was not statistically significant. CONCLUSIONS: Quantitative rheumatoid factor isotype assays and magnetic resonance imaging evaluation of erosions of the hand and wrist may be useful for investigating patients with early rheumatoid arthritis.
Adolescent↗
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↗
Changes of the lung in rheumatoid arthritis--rheumatoid pneumonia. A clinicopathological study.
The frequency and patho-histological characteristics of pulmonary changes were studied on the autopsy material of 100 patients with rheumatoid arthritis (RA). The formal pathogenesis and different stages of vasculitis, rheumatoid nodule, interstitial pneumonia, rheumatoid pleuritis, obliterative bronchiolitis, amyloidosis and the so-called rheumatoid pneumonia in the lungs is discussed. The rheumatoid pneumonia is a disseminating inflammatory lobular-sublobular process, not described previously. The frequency of rheumatoid pneumonia was 4%. The rheumatoid pneumonia is characterized by the necrotic vasculitis, fibrinoid necrosis or thrombovasculitis of the pulmonary and bronchial arterioles, and of small arteries. Because of the diminished blood supply distal to the vascular changes inflammatory foci may develop, more or less respecting the anatomic borders of pulmonary tissue. The lobular-sublobular inflammation is basically of non haemorrhagic character. Because of the recurrent nature of vasculitis, foci of inflammation in different stages can be observed in the lungs simultaneously side by side. Clinically the rheumatoid pneumonia was accompanied by severe RA, according to the frequency and severity of acute exacerbations. In all 4 cases of rheumatoid pneumonia the pulmonary process had been proven clinically and radiologically. Rheumatoid pneumonia occurred subsequent to recurrent arthritis following steroid withdrawal, and it was resistant to antibiotics.
Adult↗
Suppression of rheumatoid factor synthesis by antiidiotypic antibody in rheumatoid arthritis patients with cross-reactive idiotypes.
The effect of antiidiotypic antibody on the in vitro production of rheumatoid factor was studied in rheumatoid arthritis patients with cross-reactive idiotypic determinants. Antiidiotypic antibodies (ascites IgG) were developed against monoclonal rheumatoid factor (Ka m-RF) by a cell fusion procedure. These antibodies were idiotype-specific, since: 1) they reacted only with F(ab')2 fragment of Ka m-RF; 2) they failed to react with normal IgM without rheumatoid factor activity; and 3) their F(ab')2 fragment inhibited the rheumatoid factor activity of Ka m-RF. The antiidiotypic antibody strongly suppressed the in vitro production of rheumatoid factor by lymphocytes from unrelated rheumatoid arthritis patients with cross-reactive idiotypes. The suppression was specific, since ascites IgG failed to suppress in vitro anti-keyhole limpet hemocyanin antibody production by the lymphocytes. These results indicate that antiidiotypic antibody may influence the regulation of rheumatoid factor production in patients with rheumatoid arthritis.
Antibodies, Monoclonal↗
Effect of pregnancy on immune complexes and rheumatoid factors in patients with rheumatoid arthritis.
Rheumatoid arthritis is associated with circulating and intra-articular immune complexes and rheumatoid factors. The clinical activity of rheumatoid arthritis improves during pregnancy in the majority of women, with exacerbation following delivery. Concentrations of immune complexes, as detected by the Clq-binding assay, the Clq-solid phase assay, and the monoclonal rheumatoid factor-solid phase assay, decreased during gestation, with elevations following delivery. Concentrations of IgM-rheumatoid factor and IgG-rheumatoid factor, analyzed by radioimmunoassay, changed variably during pregnancy, increasing in some patients and decreasing in others. When examined serially before, during, and following pregnancy, changes in the concentration of circulating immune complexes and/or rheumatoid factors corresponded with the clinical changes in three patients. These observations document the significant effect of gestation on the concentration of circulating immune complexes in patients with rheumatoid arthritis. They also support the role of these laboratory tests in monitoring the clinical course of rheumatoid arthritis.
Antigen-Antibody Complex↗
High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor alpha inhibitors in rheumatoid arthritis.
OBJECTIVE: To investigate whether rheumatoid factor isotypes and anti-cyclic citrullinated peptide (anti-CCP) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor alpha (TNFalpha) inhibitors. METHODS: The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease-modifying antirheumatic drugs. Patients were treated with infliximab (n = 63), etanercept (n = 35) or adalimumab (n = 34). All patients completed 1 year of follow-up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM, IgA and IgG rheumatoid factors and anti-CCP antibodies were assessed by ELISA both before anti-TNFalpha treatment and 1 year later. RESULTS: The DAS response was reached in 66% of evaluable patients (61% infliximab, 65% etanercept and 76% adalimumab; p = 0.354). A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year. The frequency of positive tests for the different antibodies did not differ between responders and non-responders at baseline; however, significantly higher IgA rheumatoid factor levels were reported by the non-responder group (130.4 U/ml (interquartile range 13.8-276.7) v 24.8 U/ml (10.2-90.8); p = 0.003). A significant decrease (p<0.001) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment, whereas anti-CCP antibody levels were not significantly affected. CONCLUSIONS: According to the clinical response, anti-TNFalpha agents seem to reduce IgM, IgG and IgA rheumatoid factor levels. More interestingly, high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFalpha inhibitors.
Adalimumab↗
Rheumatoid factors specific for active rheumatoid arthritis.
To measure rheumatoid factors specific for patients with rheumatoid arthritis an enzyme linked immunosorbent assay (ELISA) was developed to measure rheumatoid factors in human serum that bind a cross-reactive determinant shared on human and other mammalian IgG. Rheumatoid factors that cross link human IgG and sheep IgG in a double binding ELISA were almost completely specific (greater than 99%) for rheumatoid arthritis in assays of 108 sera from patients with rheumatoid arthritis compared with 231 sera from patients with other connective tissue diseases and 365 sera from healthy subjects and patients without these diseases. Moreover, positive tests occurred primarily in patients with active arthritis (r = 0.68). In contrast, these rheumatoid factor autoantibodies were not detected in sera from most of the patients with other autoimmune diseases, including patients with systemic lupus erythematosus. These results show that rheumatoid factors identified in human sera by the double binding test are specific for active rheumatoid arthritis.
Adult↗
Rheumatoid factor and antikeratin antibody are independent from presence of DR4 or DR1 in rheumatoid arthritis.
BACKGROUND: Presence of HLA-DR4, rheumatoid factor, and antikeratin antibody may predict severe rheumatoid arthritis. OBJECTIVE: To investigate potential associations between HLA DR4, rheumatoid factor and antikeratin antibody in rheumatoid arthritis patients. PATIENTS AND METHODS: Retrospective review of 169 patients followed at the Rangueil Teaching Hospital rheumatology department for rheumatoid arthritis. RESULTS: No differences in prevalences of DR4 and DR1 were found between patients with and without rheumatoid factor or between patients with and without antikeratin antibody, suggesting that the production of rheumatoid factor and/or antikeratin antibody is not dependent on genetic factors. Substantial overlap was seen between rheumatoid factor and antikeratin antibody. All three parameters can be identified at first evaluation of a patient with joint disease. CONCLUSION: It would be of interest to evaluate the cumulative predictive value of DR4 or DR1, rheumatoid factor and antikeratin antibody at disease onset.
Arthritis, Rheumatoid↗