Granulocyte-macrophage colony-stimulating factor treatment of neutropenia associated with Felty's syndrome.
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Felty Syndrome↗
Biomedical subjects
F C Breedveld
Publications and source records attributed to F C Breedveld.
Bisphosphonates in collagen arthritis.
Bisphosphonates suppress bone destruction in various diseases. We studied the effects of 3-amino-hydroxypropylidene-1,1-bisphosphonate (APD), and dimethyl-APD in the collagen model of chronic arthritis in rats. The incidence and severity of arthritis was not lower in rats treated with APD or dimethyl-APD compared with controls. The cellular and humoral immune responses to collagen were also similar in the treated and untreated animals. In all animal groups the same bone destruction was found radiographically 42 days after immunization. This study demonstrates that bisphosphonates do not suppress the course of collagen arthritis in rats.
Animals↗
Possibilities for the immunotherapy of rheumatoid arthritis.
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Antibodies, Monoclonal↗
IgE-containing immune complexes in synovial fluid of patients with rheumatoid arthritis.
The prevalence and composition of IgE-containing immune complexes in paired synovial fluid and serum of 42 patients with classical or definite rheumatoid arthritis were studied. IgE-containing immune complexes were found in 15/42 synovial fluids; 15 sera were also positive. The correlation between serum and synovial fluid complexed IgE levels was high (r = 0.77). The mean ratio of synovial fluid/serum levels was 1.96, i.e. significantly higher than 0.33, the synovial fluid/serum ratio for alpha-2-macroglobulin (molecular weight 820 kD), which was taken as high molecular weight control protein (p less than 0.0001). Apart from IgE in immune complex form, monomeric IgE was also significantly higher in synovial fluid compared to serum (ratio = 2.94). Other constituents which could be found in the immune complexes, i.e. anti-IgE antibodies, rheumatoid factors and anticollagen antibodies, were also higher in synovial fluid than predicted. Our results suggest intra-articular production of IgE-containing complexes in the synovial fluid, in addition to possible exudation of the complexes from the serum. These findings provide further evidence for the role of IgE-containing immune complexes in rheumatoid synovitis.
Antigen-Antibody Complex↗
Significance of rheumatoid factor isotypes in seronegative rheumatoid arthritis.
In a cross-sectional study of 124 patients with definite or classical rheumatoid arthritis (RA) and negative agglutination assays, rheumatoid factor (RF) isotypes were measured using an ELISA technique. Elevated levels of IgA-RF were found in 55 patients (44%), IgG-RF in 99 (80%), and IgM-RF in 20 (16%). The levels of IgA- and IgM-RF correlated with each other (P less than 0.001). Elevated levels of IgM-RF were associated with a more severe disease course. Elevated levels of IgA-RF correlated with the occurrence of bone erosions. The results of this study suggest that in patients with RA and negative agglutination assays, both IgM- and IgA-RF are markers of disease severity.
Adult↗
Degradation of aggregates of activated C3 (C3b) by monocytes of patients with rheumatoid arthritis is related to vasculitis.
We investigated whether a decreased complement receptor expression or function of monocytes isolated from peripheral blood of 52 patients with rheumatoid arthritis (RA) and rheumatoid vasculitis (RV) could account for the previously observed diminished degradation of immune complexes by monocytes of patients with RA and RV. On average, monocytes from all patients expressed significantly less CR1, and degraded significantly less AC3b when compared with monocytes of healthy controls. In addition, monocytes from RV patients degraded significantly less AC3b when compared with monocytes from patients with RA. The expression of both CR1 and CR3 on monocytes of RV patients was lower compared with RA patients but this difference was only significant for CR3. No differences were found between AC3b degradation and the expression of CR1 and CR3 between patients with active and inactive RA. Using linear discriminant analysis on the variables AC3b, CR1 and CR3, 94% of the patients could be classified correctly as healthy controls, RA or RV, suggesting a true multi-variate relationship between these parameters and patients groups. Our results suggest that the diminished capacity of monocytes from RA patients to degrade AC3b is due partly to a decreased expression of CR1 and CR3.
Adult↗
Cytolytic activity in T cell clones derived from human synovial rheumatoid membrane: inhibition by synovial fluid.
A panel of T cell clones was derived from the synovial membrane of a patient with rheumatoid arthritis (RA). We investigated whether T cell clones with cytolytic properties were present and whether T cell cytotoxicity was influenced by the presence of synovial fluid. These issues were studied using anti-CD3 and lectin-induced cytotoxicity assays. The majority of the T cell clones derived from the synovial membrane showed cytotoxic properties although non-cytotoxic clones were also found. Three clones (N11, N6 and N15) showed strong cytotoxicity (more than 40% lysis at an effector-to-target cell ratio of 10:1) whereas three clones (N16, N4 and N14) were non-cytotoxic (less than 20% lysis at an effector-to-target cell ratio of 10:1). The induction of cytotoxicity in the anti-CD3-driven system was shown to be dependent on the dose of anti-CD3 present. When synovial fluid was added to these assays a strong inhibition of cytotoxicity was found. This inhibition of cytotoxicity was found with synovial fluid samples of RA patients, as well as with non-RA synovial fluids. Both anti-CD3 and lectin-dependent cytotoxicity assays were strongly inhibited. In conclusion, T cell clones with cytotoxic activity can be isolated from rheumatoid synovial membrane. In the presence of synovial fluid these cytotoxic cells are inhibited to exert their cytotoxic function.
Antibodies, Monoclonal↗
Dominant T-cell receptor beta-chain gene rearrangements indicate clonal expansion in the rheumatoid joint.
T-cell receptor (TcR) beta and delta gene rearrangements were studied in anti-CD3 expanded T-cell populations cultured from the synovial membrane (SM) (n = 5) or synovial fluid (SF) (n = 2) of rheumatoid arthritis (RA) patients. Dominant TcR beta-chain gene rearrangements to C beta 1 were demonstrated in all the patients tested and 1-3 expanded clones per patient were found. Clonal rearrangements to C beta 2 were detected in one SM sample (two clones) and one SF sample (one clone). The TcR delta gene was deleted in all the samples tested. We conclude that clonal dominance may be found in expanded T-cell populations from SM and SF of RA patients. Multiple clones may be present, either using the C beta 1 or C beta 2 gene segment.
Adolescent↗
Raised plasma renin and prorenin in rheumatoid vasculitis.
The value of plasma renin and its inactive precursor, prorenin, were examined as a marker for vasculitis in rheumatoid arthritis (RA). Plasma renin and prorenin rise when the renin-angiotensin system is activated; an isolated increase of prorenin may be a marker for microvascular complications in diabetes mellitus. Renin concentrations in plasma obtained from 34 patients with RA (seven with vasculitis, 27 controls) were measured under standard conditions, before and five days after stopping non-steroidal anti-inflammatory drugs; creatinine clearance was also measured. At first the median renin concentration in the patients with vasculitis was 19 (range 12-63) mU/l (normal less than 61 mU/l) and in the controls 9 (3-43) mU/l. The median prorenin concentration in patients with vasculitis was 233 (144-428) mU/l (normal less than 358 mU/l) and in the controls 144 (25-364) mU/l. Renin and prorenin concentrations increased significantly in both groups after withdrawal of nonsteroidal anti-inflammatory drugs. The creatinine clearance was similar in both groups and did not correlate with renin concentrations. In conclusion, it was found that, unlike patients with diabetes mellitus, patients with RA with vasculitis had slightly raised concentrations of both renin and prorenin. These findings signal activation of the renin-angiotensin system and might indicate early cardiac or renal involvement by vasculitis.
Aged↗
Cutaneous immunofluorescence in ankylosing spondylitis. Absence of correlation with disease activity.
Biopsy specimens of normal skin from 43 patients with ankylosing spondylitis (AS) were studied for immunoglobulin and complement deposition by immunofluorescence and for histological abnormalities by light microscopy. The results were compared with those of 17 healthy subjects. Perivascular deposits of IgA, IgG, IgM and C3 were found in 26, 47, 56 and 33%, respectively, of the patients with AS. Skin deposits of IgA, IgG and C3 occurred significantly more frequently in patients with AS compared to healthy subjects. Perivascular mononuclear cell infiltration was found in only 8 (19%) of the patients with AS. The results of both immunofluorescence and histologic studies did not correlate with disease duration, disease activity, extraarticular features or the presence of circulating immune complexes. Our findings suggest a role of humoral immunopathological mechanisms in AS but also show that cutaneous immunofluorescence cannot serve as a marker of disease activity.
Adult↗
Minocycline treatment for rheumatoid arthritis: an open dose finding study.
Ten patients with active definite or classical rheumatoid arthritis (RA) were treated with oral minocycline (maximal daily dose 400 mg) during 16 weeks in an open study. Seven patients reported side effects (in most cases vestibular) leading to premature discontinuation in one. Half of the efficacy variables improved significantly after 4 weeks of therapy. At the end of the study all variables were significantly changed compared with their pretreatment values. We conclude that minocycline may be beneficial in RA. This effect needs to be confirmed in controlled studies.
Administration, Oral↗
Anti-endothelial cell antibodies in patients with rheumatoid vasculitis.
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Antibodies↗
Collagen arthritis in the rat is initiated by CD4+ T cells and can be amplified by iron.
The role of iron in arthritis was studied by administering ferric citrate (Fe-cit) to age-matched, female Sprague-Dawley rats immunized with chick type II collagen on Day 0. Rats received intravenously (iv) either Fe-cit (7.7 mg/kg body wt) or an identical concentration of sodium citrate on varying days after immunization. Transferrin saturation peaked (88-95%) 1 hr post-Fe-cit and returned to baseline values within 24 hr. Injection of Fe-cit on either Day 3 or Day 5, but not on Day 7 or Day 9, significantly (P less than 0.03) increased the incidence of arthritis. Synovium from the infrapatellar fat pad was harvested on Days 0-10 for analysis by immunocytochemistry. The inceptual morphologic change in the synovium following collagen immunization in rats not injected iv was an increase in the number of CD4+ and transferrin receptor+ mononuclear cells in perivascular regions; compared to Day 0 both cell types had increased two- to threefold by Day 3. On Day 7, an increase in CD8+ mononuclear cells occurred and the first polymorphonuclear leukocytes were noted. These alterations resulted in a peak in the CD4-CD8 ratio on Day 3, with a gradual decline thereafter. Although Fe-cit administration promoted the ingress of these mononuclear cells, it did not change the CD4-CD8 ratio significantly or recruit polymorphonuclear leukocytes into the joint tissue. Serum antibody titers to type II collagen, measured 20 days after immunization by an enzyme-linked immunosorbent assay, and delayed-type hypersensitivity to collagen, measured by a radiometric ear assay on Day 23, did not differ significantly between the groups. As well as showing that the initial intrasynovial event in collagen arthritis is perivascular infiltration by members of the CD4+ T cell subset displaying a phenotypic sign of activation, these findings demonstrate that iron administered at a critical time after immunization enhances the induction of collagen arthritis. The coincidence of this brief period of susceptibility with maximum CD4-CD8 ratios within the synovium and its occurrence prior to the stage of neutrophil infiltration are consistent with the possibility that the augmenting effect of iron is mediated by the inducer T cell subset.
Animals↗
Quantitative detection of class-specific rheumatoid factors using mouse monoclonal antibodies and the biotin/streptavidin enhancement system.
An enzyme-linked immunosorbent assay (ELISA) for the quantitative detection of rheumatoid factors (RF) was developed using mouse monoclonal antibodies against human IgG, IgA and IgM together with the biotin/streptavidin enhancement system. One hundred and eight patients with rheumatoid arthritis (RA) of whom 47 had a positive serum latex agglutination assay, 100 healthy controls and 95 diseased controls (25 systemic lupus erythematosus (SLE), 25 ankylosing spondylitis, 20 osteoarthritis and 25 bronchial asthma) were evaluated for the presence of IgG-, IgA- and IgM-RF by ELISA. Elevated levels of IgG-, IgA-, and IgM-RF could be demonstrated in respectively 94%, 91% and 98% of serum samples from RA patients with a positive latex test and in 72%, 69% and 8% of serum samples from RA patients with a negative latex test. In the latter patient group, increased levels of one or more RF isotypes could be detected in 82% of the patients. Except for the presence of IgG-RF in serum of 20% of the SLE patients, increased levels of RF isotypes were present in less than 5% of the diseased controls. Highly significant correlations were found between serum IgM-RF levels as detected by ELISA and those of the latex and the Rose-Waaler agglutination assays. Positive correlations were also found between the serum levels of the three RF isotypes investigated and between the levels of RF isotypes as measured in serum and synovial fluid of the same patient. Compared to agglutination assays, the ELISA for the quantitative detection of RF isotypes is a more reproducible and sensitive test which avoids some of the problems encountered in earlier ELISA methods.
Agglutination Tests↗
Anterior spinal artery syndrome in systemic lupus erythematosus.
We present a patient with systemic lupus erythematosus who developed an anterior spinal artery syndrome (ASAS) in association with livedo reticularis, leg ulcerations and thrombocytopenia. Low serum titres of anticardiolipin antibodies were detectable throughout the course of this disease. The patient recovered from the first episode of ASAS under corticosteroid treatment but remained paralytic after a second episode. Repeated magnetic resonance imaging of the spinal cord failed to show altered signal intensity.
Adolescent↗
T-cell phenotypes after stimulation of human mononuclear cells by pokeweed mitogen or pokeweed mitogen bound to erythrocytes.
Stimulation of human peripheral blood mononuclear cells (PBMC) by pokeweed mitogen bound to erythrocytes (E-PWM) has been found to result in an increased blast cell formation, lymphocyte proliferation, and enhanced immunoglobulin production, compared to stimulation of PBMC by PWM. Using flow cytometric analysis we compared the T helper/inducer (CD4+) to T suppressor/cytotoxic (CD8+) cell ratios of PBMC after stimulation by PWM and by E-PWM. E-PWM was found to induce significantly lower CD4+:CD8+ ratios on days 6 and 9 of the culture than PWM did. This effect was due predominantly to a relative increase in CD8+ T cells after stimulation of PBMC by E-PWM, compared with stimulation by PWM. However, the increase in T suppressor/cytotoxic cells on days 6 and 9 after E-PWM stimulation was accompanied by a simultaneous relative decrease in CD4+/2H4+ T cells (T suppressor-inducer cells) and by a relative decrease in CD8+/Leu-15+ T cells (CD4+/2H4+ independent T suppressor cells) on day 9, compared with stimulation by PWM. These results suggest that the greater immunoglobulin production after stimulation of PBMC by E-PWM than by PWM may be the result of a relative lack of suppression on fully differentiated B cells.
Antigens, Differentiation, T-Lymphocyte↗
Rheumatoid arthritis with eosinophilic fasciitis and pure red cell aplasia.
A case of longstanding rheumatoid arthritis with concurrent development of eosinophilic fasciitis and pure red cell aplasia is described. A simultaneous occurrence of all 3 disorders has not been reported. Treatment with moderate dosages of prednisone resulted in a prompt and complete remission of both the fasciitis and the selective marrow aplasia.
Arthritis, Rheumatoid↗