[Clinical symptoms and diagnostic criteria of systemic lupus erythematosus].
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Biomedical subjects
Publications and source records attributed to R Yokohari.
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Clinical features and prognosis of sixty patients with connective tissue disease accompanied by pulmonary hypertension (PH) (26 MCTD, 20 SLE, and 14 PSS) reported retrospectively by multi-institutions were compared. Though the obtained data were incomplete and lacking in uniformity, no significant difference in the clinical features among the three diseases were observed except high incidence of pulmonary fibrosis and low % VC in PSS and PH patients. Statistically significant difference, however, was observed between live and dead patients of three diseases gathered in post sternal pain, pulmonary diastolic murmur, right ventricular hypertrophy on ECG and mean pressure of pulmonary artery. Higher incidence of anti-nRNP antibody was observed in SLE with PH and PSS with PH patients than with the general population. A quicker occurrence of PH and shorter survival time were observed in MCTD patients with PH than in SLE and PSS patients with PH.
Rheumatoid factors (RF) have been shown to have considerable heterogeneity and bind with IgG as well as with a variety of substances such as nuclear histone, non-histone nuclear protein, nitrophenyl groups or ssDNA. We describe evidence that polyclonal RF cross-reactive with ssDNA (CRRF) are widely distributed in a variety of rheumatic diseases, and that their serum level is significantly higher in rheumatoid arthritis (RA) with extra-articular disease. Although the mechanism of the cross-reactivity is not clear, the presence of CRRF could be a serological feature of a clinical subset of RA. The high prevalence rate of CRRF in RA with extra-articular disease also suggests its pathogenetic role in the extra-articular manifestation of this disease.
Antibodies to dsDNA are characteristically present in serum from patients with systemic lupus erythematosus (SLE), and have been shown to have the capacity to react with various molecules bearing repeating negative charges. After a number of polymeric or monomeric molecules with differently charged groups and hydrophobic molecules had been coupled covalently as ligands on cellulose gel, the adsorption capacities of the ligands for anti-dsDNA antibodies were evaluated. It was found that gels coupled with polyanionic dextran sulphate (DXS) and polyacrylic acid (PA) and monoanionic sulphanilic acid (SA) absorbed anti-dsDNA antibodies effectively. DXS gel also adsorbed antibodies to ssDNA and heparan sulphate, antigens with repeating negatively charged moieties, while no ligand was able to adsorb anti-nRNP antibodies. The finding that DXS gels adsorbed anti-dsDNA antibody in proportion to their charge density, and that the interaction between anti-dsDNA and DXS gel is broken readily by an increase in ionic strength, indicated that the binding is ionic in nature. Moreover, virtually all F(ab')2 anti-dsDNA became adsorbed onto the DXS gels, suggesting that the binding occurred via specific antigen-binding sites on the antibody molecule. Binding of these polyanion-binding autoantibodies with anionic sites in the glomerular basement membrane may therefore cause the tissue damage observed in SLE.
Adherent synovial cells from both 13 patients without rheumatoid arthritis (RA) (gout, osteoarthritis and meniscal lesion) and 8 patients with RA consisted of dendritic cells, macrophage-like cells and fibroblast-like cells after cloning in a similar fashion as reported in our previous paper. All the adherent synovial cells from patients without RA did not release interleukin 1 (IL-1) beta and prostaglandin E2 (PGE2) spontaneously, while those cells released comparable amounts of IL-1 beta, but not PGE2 to RA cells after type II collagen stimulation. Only the synovial cells from RA, irrespective of morphology and cloning, released IL-1 beta and PGE2 without stimulation. Nonrheumatoid synovial cells may differ functionally from RA cells.
A dextran sulphate gel column removed anti-double-stranded DNA antibodies (anti-dsDNA) selectively, efficiently, and safely from the circulation of a patient with systemic lupus erythematosus (SLE). The mechanism of the removal is thought to be due to cross reactivity of anti-dsDNA with dextran sulphate, which has negatively charged units. Selective removal of anti-dsDNA is expected to contribute not only to the treatment but also to elucidation of the pathogenesis of SLE.
The possible association between HLA-DR4 and interleukin 1 beta (IL-1 beta) secretion from peripheral blood monocytes was analyzed using 34 female patients, with definite rheumatoid arthritis (RA). RA monocytes in serum-free medium or medium supplemented with 10% fetal calf serum secreted IL-1 spontaneously. The level of secretion was enhanced by stimulation with pyrogen-free type II collagen as determined by comparison with 30 healthy individuals matched for age and sex. No association between HLA-DR4 and spontaneous or stimulated IL-1 release from RA monocytes was observed.
A 28 year-old female patient who has been diagnosed as having systemic lupus erythematosus (SLE) developed an acute dissecting aneurysm of the aorta (DeBakey type I). The long-term, large dose corticosteroid therapy (i.e., accumulative dose of about 60 g) administered for the treatment of lupus nephritis (WHO class III----IV) was considered to be responsible for a hypercholesterolemia (300-560 mg/dl) and a steroid-dependent hypertension (WHO class III) in this patient. The autopsy findings for the aorta were compatible with atherosclerotic changes but not with lupus arteritis. While atherosclerotic cardiovascular complications have been considered to be rare in patients with SLE, a growing body of evidence suggests that the incidence of such a complication may be increasing along with a dramatic improvement in the longevity of patients with SLE after an introduction of a large dose, long-term corticosteroid therapy.
Monocyte-depleted mononuclear cells (MNC) from healthy subjects synthesized IgM-class antibody to single-stranded DNA (anti-ssDNA) at significantly higher levels than unfractionated MNC. The increased production of IgM anti-ssDNA by monocyte-depleted normal MNC was inhibited to a greater degree than total IgM by addition of supernatants from autologous monocytes. Moreover, supernatants obtained from normal monocytes cultured with indomethacin retained this suppressive effect on IgM anti-ssDNA antibody production, suggesting that prostaglandin E2 may not be involved in the suppression. These results indicate that B cells programmed to produce IgM anti-ssDNA are present in the normal B cell repertoire, but may be suppressed by monocytes or by a soluble factor (or factors) from the monocytes.
The regulatory role of normal monocytes in the production of rheumatoid factor (RF) was investigated. Monocyte depletion from normal mononuclear cells (MNC) resulted in an elaboration of IgM RF in 18 of 20 subjects. The increased RF production was inhibited by the addition to the cultures of adherent cells or their culture supernatants. These observations demonstrate the suppressive role of normal monocytes in the production of RF. Supernatants obtained from normal monocytes cultured with indomethacin could suppress the RF production, suggesting that prostaglandin E2 may not be involved in the regulation of IgM RF production.
Antibodies to double-stranded (ds) DNA are characteristically present in serum from patients with systemic lupus erythematosus (SLE). Recently, anti-dsDNA antibodies have been shown to have the capacity to react with a diversity of molecules with repeating negative charges. Using the anionic dye Cibacron blue F3GA, bound to crosslinked agarose, we analysed the nature of antibodies capable of reacting with this dye in serum samples from patients with various rheumatic diseases. The dye-antibody complex could easily be split by eluting with solutions of increasing ionic strength, suggesting that the interaction is ionic in nature. Pepsin-digested F(ab')2 antibodies retained the capacity to bind Cibacron blue, confirming that the binding occurred via antigen-binding sites on the antibody molecule. The eluates obtained from dye-ligand chromatography of active SLE sera contained antibodies to both dsDNA and heparan sulfate, while those of sera from patients with other non-SLE rheumatic diseases contained antibodies only against heparan sulfate. Furthermore, the dye-ligand eluates of sera from patients with active SLE and other non-SLE rheumatic diseases were found to contain increased amounts of IgG. In one patient with SLE, levels of antibodies to dsDNA and heparan sulfate, and the amounts of total IgG in dye-ligand eluates, were shown to be correlated with disease activity.
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2-dimensional flow cytometric analysis of the peripheral blood T lymphocytes from 20 patients with systemic lupus erythematosus showed a significant increase in the percentage of Leu 2a+ 15- cytotoxic subset irrespective of disease activity compared to 35 age and sex matched healthy individuals. The percentage of Leu 2a+ HLA-DR + cells also increased significantly in both patients with active and inactive disease compared to the controls. In contrast, both the relative and absolute number of Leu 3a+ 8+ cell (suppressor/inducer T cell) showed a significant reduction in active and inactive disease if compared to controls. All of these changes were more drastic in the patients with active disease.
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In earlier studies we showed that the C1q-binding IgG in the sera from patients with systemic lupus erythematosus (SLE) tested by C1q solid-phase radioimmunoassay is cofractionated with monomeric IgG on gel filtration and mostly binds to C1q via the F(ab')2 region. In this study, we found that C1q, even when stripped of its immune complex-binding globular regions by pepsin digestion, retained a substantial part of its ability to bind IgG from SLE sera, suggesting that the collagen-like region of C1q is involved in binding to the SLE IgG. Heat-inactivation of C1q also failed to abolish its ability to bind IgG from SLE sera. In contrast, the binding of C1q to heat-aggregated IgG was completely abrogated by these treatments. In addition, the reaction of heat-aggregated IgG with the solid-phase C1q was markedly dependent on ionic strength whereas the binding of IgG from SLE sera with the solid-phase C1q persisted at high concentrations of salt. These findings suggest that the Clq-binding IgG in SLE sera is, at least in part, antibody directed against the collagen-like region of C1q.
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The 1982 American Rheumatism Association revised criteria for the classification of systemic lupus erythematosus were tested on Japanese patients. Sensitivity and specificity data were comparable with those presented in the development of the revised criteria by the American Rheumatism Association. Complement determinations were evaluated for their ability to improve the criteria for the diagnosis of early systemic lupus erythematosus.