Transformation of human lymphocytes in vitro by autologous and allogeneic rheumatoid synovial fluids.
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To assess the possible participation of cellular immune mechanisms in the pathogenesis of rheumatoid arthritis (RA) in vitro studies of the blastogenicity of rheumatoid and non-rheumatoid synovial fluids for human peripheral blood lymphocytes were conducted. In autologous cultures it was found that 13 of 19 rheumatoid fluids induced significant lymphocyte blastogenesis, whereas only 1 of 13 nonrheumatoid fluids induced such a response. In allogeneic cultures rheumatoid fluids induce significant blastogenesis of RA lymphocytes in 18 of 23 experiments, and of non-RA lymphocytes in 8 of 18 experiments. By contrast, nonrheumatoid fluids induced significant blastogenesis of RA lymphocytes in 2 of 13 experiments, and of non-RA lymphocytes in 1 of 14 experiments. The blastogenicity of fluids was found to correlate significantly with the presence therein of immunofluorescent intracellular inclusions of immunoglobulin and complement. These studies support the concept that the presence of immune complexes in the majority of rheumatoid synovial fluids might render the latter blastogenic for human lymphocytes in vivo, thereby perpetuating rheumatoid synovitis. (+info)
Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin V(H) genes show frequent use of V1-69 with distinctive CDR3 features.
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Salivary gland mucosa associated lymphoid tissue (MALT) type lymphomas are B-cell neoplasms that develop out of a reactive infiltrate, often associated with Sjogren's syndrome. Previous reports from our laboratory involving 10 patients suggested these lymphomas expressed a restricted immunoglobulin (Ig) V(H) gene repertoire with over use of V1-69 gene segments. To better determine the frequency of V1-69 use and whether there may also be selection for CDR3 structures, we sequenced the V(H) genes from 15 additional cases. Over half of the potentially functional V(H) genes (8 of 14) used a V(H)1 family V1-69 gene segment, whereas the other cases used different gene segments from the V(H)1 (V1-46), V(H)3 (V3-7, V3-11, V3-30.3, V3-30.5), and V(H)4 (V4-39) families. The 8 V1-69 V(H) genes used 5 different D segments in various reading frames, but all used a J4 joining segment. The V1-69 CDR3s showed remarkable similarities in lengths (12-14 amino acids) and stretches of 2 to 3 amino acids between the V-D and D-J junctions. They did not resemble CDR3s typical of V1-69 chronic lymphocytic leukemias. This study extends our earlier work in establishing that salivary gland MALT lymphomas represent a highly selected B-cell population. Frequent use of V1-69 appears to differ from MALT lymphomas that develop at other sites. The high degree of CDR3 similarity among the V1-69 cases suggests that different salivary gland lymphomas may bind similar, if not identical epitopes. Although the antigen specificities are presently unknown, similar characteristic CDR3 sequences are often seen with V1-69 encoded antibodies that have anti-IgG or rheumatoid factor activity. (Blood. 2000;95:3878-3884) (+info)
Respiratory involvement in systemic lupus erythematosus. A clinical and immunological study.
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Thirty patients fulfilling conventional criteria for systemic lupus erythematosus and who presented with extensive pleural and pulmonary involvement were studied retrospectively. Four overlapping patterns of respiratory disease were identified and observations were made on their clinical presentation, radiographic abnormalities and response to treatment. A low incidence of severe renal disease was found in this series of patients and this was in keeping with the general finding of low serum binding using native DNA in a globulin Farr-binding technique (greater than 20% binding in only 4/21 (19%) of the series) and normal or elevated serum complement (C3) levels. Precipitating antibody detected by double diffusion and counter-current immunoelectrophoresis and probably reacting in most cases with single-stranded DNA was, however, detected in 66% of pretreatment serum samples tested. This evidence supports the idea that different types of anti-nuclear antibody may be associated with different clinical manifestations seen within a group of patients who broadly fulfil the criteria for SLE. (+info)
Measles antibodies and autoantibodies in autoimmune disorders.
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Measles CF antibodies have been examined in the sera of patients with a variety of clinical disorders associated with the production of autoantibodies. Previous reports of high-titre reactions in DLE and chronic active hepatitis have been confirmed, the titres in the latter disorder being particularly elevated. Mean antibody titres to measles in patients with rheumatoid arthritis were significantly lower than in matched controls, and an inverse correlation between measles antibody levels and serum globulin levels was found. Measles antibody titres in patients with myasthenia gravis and primary biliary cirrhosis did not differ significantly from those found in controls. However, subdivision of patients with rheumatoid arthritis, myasthenia gravis and primary biliary cirrhosis showed that the presence of anti-nuclear antibody (ANA) was associated with significantly increased measles antibody levels compared with the ANA-negative sera. The presence of gastric parietal cell antibody or thyroid microsomal antibody did not appear to be associated with increased measles antibody levels, whether or not they occurred in association with previous anaemia or thyroid disease. Possible explanations for these findings in terms of immune complex formation and immune hyper-reactivity are discussed. (+info)
Effect of penicillamine treatment on immune complexes in two cases of seropositive juvenile rheumatoid arthritis.
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A correlation has previously been observed between the presence of enhancing complexes and cutaneous vasculitis in rheumatoid arthritis. Two parients with seropositive juvenile rheumatoid arthritis are described in whom enhancing complexes were detected before the appearance of cutaneous vasculitis. Their contrasting response to penicillamine is discussed in relation to the role of of rheumatoid factor and antinuclear antibodies. (+info)
Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis.
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OBJECTIVE: An elevated acute-phase response is associated with increased radiologic damage in rheumatoid arthritis (RA), but development of damage in previously normal joints ("new joint involvement") has not previously been investigated. This study was undertaken to investigate the hypothesis that when there is suppression of disease activity as judged by the C-reactive protein level, new joint involvement is reduced to a greater extent than is progression in already damaged joints ("damaged joint progression"). METHODS: Three hundred fifty-nine patients with active RA were studied as part of a 5-year randomized, prospective, open-label study of disease-modifying antirheumatic drug therapy. Time-averaged CRP was calculated from samples obtained every 6 months, and patients were divided into groups with CRP values of <6, 6-<12, 12-<25, and > or =25 mg/liter. Radiographs of the hands and feet were scored by the Larsen method; a damaged joint was defined as one with a score of > or =2. RESULTS: The rank correlation between time-integrated CRP and increase in Larsen score was 0.50; the correlation increased to 0.59 for patients entering the study with disease duration of < or =2 years. The percentage of new joint involvement over 5 years varied markedly with time-integrated CRP, from 7.3% in the CRP <6 mg/liter group to 39.1% in the CRP > or =25 mg/liter group (5.4-fold increase). The percentage of damaged joint progression increased from 26.1% in the CRP <6 mg/liter group to 41.6% in the CRP > or =25 mg/liter group (1.6-fold increase). CONCLUSION: The results of this study provide further confirmation that high CRP levels over time are associated with greater radiologic progression. Although radiologic progression still occurred in both previously normal and damaged joints despite the presence of normal CRP levels, this consisted of proportionately less new joint involvement compared with damaged joint progression. These findings support the idea that disease-suppressive therapy should be instituted at an early stage in patients with RA, before erosive damage has occurred. (+info)
Immune complexes present in the sera of autoimmune mice activate rheumatoid factor B cells.
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The fate of an autoreactive B cell is determined in part by the nature of the interaction of the B cell receptor with its autoantigen. In the lpr model of systemic autoimmunity, as well as in certain human diseases, autoreactive B cells expressing rheumatoid factor (RF) binding activity are prominent. A murine B cell transgenic model in which the B cell receptor is a RF that recognizes IgG2a of the j allotype (IgG2aj), but not the b allotype, was used in this study to investigate how the form of the autoantigen influences its ability to activate B cells. We found that sera from autoimmune mice, but not from nonautoimmune mice, were able to induce the proliferation of these RF+ B cells but did not stimulate B cells from RF- littermate controls. The stimulatory factor in serum was found to be IgG2aj, but the IgG2aj was stimulatory only when in the form of immune complexes. Monomeric IgG2aj failed to stimulate. Immune complexes containing lupus-associated nuclear and cytoplasmic autoantigens were particularly potent B cell activators in this system. Appropriate manipulation of such autoantibody/autoantigen complexes may eventually provide a means for therapeutic intervention in patients with certain systemic autoimmune disorders. (+info)
Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis.
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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. (+info)