Liver disease in rheumatoid arthritis and Sjogren's syndrome. Prospective study using biochemical and serological markers of hepatic dysfunction.
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Inter-relationships of biochemical and immunological tests of liver function have been studied in a prospective study of 216 patients with rheumatoid arthritis (RA), 32 patients with Sjogren's syndrome, and 27 patients with the sicca syndrome, and these results have been compared with those obtained 289 patients with osteoarthrosis or with a form of seronegative polyarthropathy. In general the prevalence of abnormalities in serum alkaline phosphatase, bromsulphthalein excretion, smooth muscle antibody, and mitochondrial antibody in the former three groups was higher than in patients with osteoarthrosis. Patients with Sjogren's syndrome with RA had a higher prevalence of abnormalities of bromsulphthalein excretion, salivary duct antibody than patients with the sicca syndrome. Patients with RA had a higher pervalence of rheumatoid factor than those with the sicca syndrome. Patients with a positive smooth muscle or mitochondrial antibody were found to have a higher prevalence of hepatomegaly and splenomegaly, of abnormal liver function tests, of other autoantibodies, and of histological abnromalitis of liver than those in whom these tests were negative. (+info)
Immunopathological changes in rheumatoid arthritis and other joint diseases.
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A comparative study of the distribution of immunoglobulins G, M, and A and C3 in the synovium and inside synovial fluid leucocytes and of the relative levels of IgG, IgM, AND C3 in paired samples of serum and synovial fluid from both seropositive and seronegative patients with rheumatoid arthritis and other types of non-infective synovitis shows that although there is no distinctive immunopathological feature of rheumatoid arthritis, the incidence of immune complexes containing IgG and IgM with and without detectable C3 in the affected synovium or inside synovial fluid granulocytes is higher in rheumatoid arthritis and especially so in seropositive cases. The mean level of C3 in synovial fluid from patients with rheumatoid arthritis is lower than that from the group without rheumatoid arthritis. In contrast to previous reports, extracellular clumps of IgA could be detected in the affected synovium of a number of affected patients. Aggretated human IgG could be bound by some of the synovial biopsies and synovial fluid leucocytes from both seropositive and seronegative rheumatoid arthritis patients. Antinuclear factor and rheumatoid factor could be detected in the synovial fluid but not in the serum of several patients suggesting either selective sequestration or local synthesis of antinuclear and rheumatoid factors in the affected joints. (+info)
MIF production of lymphocytes from patients with rheumatoid arthritis with antigen-antibody complexes.
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Immune complexes, human erythrocytes coated with human IgG antibody, inhibit the migration of lymphocytes from rheumatoid arthritis (RA) patients. No correlation could be observed between migration inhibition and Waaler-Rose titre (sheep cell agglutination titre) in inidvidual patients. Production of migration inhibitory factor (MIF) could be detected in 16 of 20 cultures of RA lymphocytes incubated with antigen-antibody complexes, when the supernates were tested with guinea pig macrophages. Only two supernates of healthy persons showed migration inhibition activity under these conditions. The results suggest that migration inhibition by antigen antibody complexes in RA represents a true reaction of delayed hypersensitivity. (+info)
Autoantibodies in childhood connective tissue diseases and in normal children.
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The prevalence of nine serum autoantibodies has been studied in 117 children with various connective tissue disorders and in 134 normal controls. In juvenile rheumatoid arthritis rheumatoid factor was present in 5%, and antinuclear factor in 4%, compared with an incidence of 4% and 0% respectively in controls. In Henoch-Schonlein purpura there was little evidence of associated autoimmune disorder. Gastric parietal cell and thyroid microsomal antibodies were found in 9% and 10% of our control population, but the significance of this is not clear. It is concluded that in children the presence or absence of autoantibodies as diagnostic criteria should be interpreted with the greatest caution. (+info)
Prediction of disease progression in early rheumatoid arthritis by ICTP, RF and CRP. A comparative 3-year follow-up study.
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OBJECTIVE: To test the predictive value of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP; a marker of type I collagen degradation), rheumatoid factor (RF) and C-reactive protein (CRP) for disease progression in patients with early rheumatoid arthritis (RA) METHOD: We tested the value of baseline values of RF, CRP and ICTP for the prediction of radiological joint progression over 3 yr in 63 consecutive patients with early RA who were treated with the 'saw-tooth strategy'. RESULTS: Age- and sex-adjusted risks as odds ratios (95% confidence intervals) of elevated serum ICTP, RF positivity and increased CRP for progressive joint disease (defined as an increase of > 20 in Larsen's index on radiographs of the hands and feet) were 3.9 (1.3, 11.9), 3.9 (1.0, 15.5) and 2.6 (0.9, 7.5), respectively. Better prediction was achieved when the tests were used in combination, and where there was both elevated ICTP and positive RF the odds ratio was 9.1 (2.5, 32.9). This test combination showed good sensitivity and specificity (71 and 77%, respectively), with a positive predictive value of 65% and a likelihood ratio of 3.1. CONCLUSION: This kind of risk profile, in which the tests used reflect different aspects of the disease process, may be useful in early disease assessment to find patients who will need the most active drug therapy. (+info)
Prognostic factors in early rheumatoid arthritis.
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The current paradigm for rheumatoid arthritis suggests that persistent synovitis leads to erosive joint damage, progression of which results in functional disability. Studies of X-ray progression followed for 1-9 yr have shown that 40-83% of subsequent progression can be predicted by a combination of prognostic factors such as joint involvement, high levels of C-reactive protein and rheumatoid factor (RF) positivity. There are similar findings for predictors of functional disability in studies followed for 2-15 yr. The most consistent prognostic feature is RF positivity, which is equally important in predicting joint damage and functional disability. Immunoglobulin A RF and the co-presence of RF with anti-keratin or anti-filaggrin antibodies may increase levels of prediction. Added value of genetic predictors over that of RF remains inconclusive. Therefore, therapeutic management should be individualized. Cases with active disease and seropositive RF tests merit aggressive therapy; conversely, cases with little synovitis and seronegative tests require conservative management. (+info)
Autoantibody activity of IgG rheumatoid factor increases with decreasing levels of galactosylation and sialylation.
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The occurrence of N-linked oligosaccharides lacking galactose is significantly higher than normal in serum IgG of patients with rheumatoid arthritis (RA) in whom rheumatoid factor (RF), an autoantibody against autologous IgG, has been detected. In the present study, IgGs with and without RF activity (IgGRF and non-RF IgG, respectively) were prepared from sera of RA patients, and their oligosaccharide structures were characterized in order to investigate the relationship between RF activity and glycosylation. Three IgGRF fractions and a non-RF IgG fraction were obtained based on their ability to bind to an IgG-Sepharose column. The specific RF activity, as measured by immunoassays, was highest in the IgGRF fraction, which bound most avidly to the IgG-Sepharose. When the oligosaccharides were released by hydrazinolysis, and analyzed by MALDI-TOF mass spectrometry and HPLC, in combination with sequential exoglycosidase treatment, all the IgG samples were found to contain a series of biantennary complex-type oligosaccharides. The incidence of galactose-free oligosaccharides was significantly higher in both IgGRFs and non-RF IgG from RA patients compared with IgG from healthy individuals. In all IgGRFs, the levels of sialylation and galactosylation were lower than those in non-RF IgG from RA patients; the sialylation of non-RF IgG was the same as that of IgG from healthy individuals. In addition, the decreases in galactosylation and sialylation of oligosaccharides in IgGRF correlated well with the increase in RF activity. These findings could contribute to our understanding of the mechanisms of IgG-IgG complex formation and the pathogenicity of these complexes in RA patients. (+info)
Association of rheumatoid factors and anti-filaggrin antibodies with severity of erosions in rheumatoid arthritis.
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OBJECTIVES: To evaluate and to compare the association of two types of autoantibodies-rheumatoid factors (RF) and anti-filaggrin antibodies (AFA)-with clinical severity and joint damage progression in rheumatoid arthritis (RA) patients. METHODS: In a cross-sectional study, we determined RF and AFA titres in 199 RA patients and 65 controls. Erosions apparent on X-rays were quantified using the Larsen score in 143 patients, and the distribution of these scores was studied according to disease duration in patients who were positive and negative for RF and AFA. RESULTS: RF were detected in 72% and AFA in 47% of RA patients. AFA were highly specific for RA (100%). RF positivity was correlated with the presence of subcutaneous nodules, sicca syndrome and the severity of erosions for a given disease duration. AFA positivity was correlated only with the presence of the HLA-DRB1 shared epitope. CONCLUSIONS: Since no significant correlation was observed between joint damage progression and AFA positivity, the determination of AFA does not appear to be useful in assessing the prognosis of RA. However, AFA, which appear early in RA, could be helpful for the diagnosis of RA in patients who do not fulfil four American College of Rheumatology criteria. (+info)