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Biomedical subjects

F C Breedveld

Publications and source records attributed to F C Breedveld.

At least 379 records · Page 21Linked to original sources
PubMed1991

Methods for the detection of anti-endothelial antibodies by enzyme-linked immunosorbent assay.

In order to obtain a routine simple screening test for the detection of anti-endothelial antibodies (AEA) we developed a highly reproducible and sensitive enzyme-linked immunosorbent assay (ELISA) on fixed endothelial hybridoma cells. Detection of AEA with this type of monolayer appeared to be superior to ELISAs with monolayers of human umbilical vein endothelial cells, unfixed endothelial hybridoma cells or assays with membranes of endothelial cells. Glutaraldehyde treated endothelial hybridoma cells are most appropriate for use in ELISA procedures to detect AEA because the endothelial hybridoma cells are easy to culture, form a constant antigenic source and when plated and fixed to microtitre plates they can be stored without losing their ability to bind AEA.

Arthritis↗
PubMed1991

Elimination of soluble 123I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1.

Using soluble 123I-labeled aggregates of human IgG (123I-AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of erythrocyte complement receptor type 1 was associated with less binding of 123I-AHIgG to erythrocytes and a faster initial rate of elimination of 123I-AHIgG (mean +/- SEM half-maximal clearance time 5.23 +/- 0.2 minutes, versus 6.58 +/- 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen. However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of 123I-AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE.

Adolescent↗
PubMed1991

Association of HLA-DR4 with a more progressive disease course in patients with rheumatoid arthritis. Results of a followup study.

The association between HLA-DR antigens and rheumatoid arthritis (RA) was investigated in a well-characterized cohort of RA patients who were followed from the beginning of the disease (mean followup 6 years). The frequencies of HLA-DR antigens in patients with possible or probable RA (n = 49) were similar to those in controls. In patients with definite RA (n = 134), the frequencies of DR1, DR4, and DRw53 were increased, whereas the frequencies of DR2, DR3, DRw6, DRw13, and DRw52 were decreased, compared with controls. Comparison of HLA-DR frequencies in patients with definite RA subclassified according to the severity of the disease at the end of the followup period revealed a difference only in the frequency of DR4, which was increased in patients with progressive RA (59.2%) compared with those who had mild RA (34.8%). Further analysis showed that, compared with DR4-negative RA patients, DR4-positive patients had more swollen joints, higher scores on the Ritchie articular index, the Health Assessment Questionnaire, and the Steinbrocker functional classification, more radiologic abnormalities, and more use of second-line drugs. Also, the rate of progression of radiologic abnormalities, functional classification, and use of second-line drugs was higher in DR4-positive patients. We conclude that DR4 is associated with a more severe disease course, and is a prognostic marker in early RA.

Adult↗
PubMed1991

Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal sites.

Elevated serum levels of IgA, IgA1, and IgA2 rheumatoid factors (RF) were demonstrated by enzyme-linked immunosorbent assay in 69%, 73%, and 36%, respectively, of 100 patients with rheumatoid arthritis (RA), whereas fewer than 5% of 100 healthy donor sera contained elevated levels of these RFs. In serum samples from 125 controls with 4 different chronic diseases (systemic lupus erythematosus, ankylosing spondylitis, bronchial asthma, and polyarteritis nodosa), levels of IgA-, IgA1-, and IgA2-RF were found to be increased in 7%, 7%, and 8%, respectively. Comparison of RF levels in samples of serum, synovial fluid (SF), and saliva from RA patients indicated local production of both IgA-RF subclasses in salivary glands and in synovial tissue. Significant positive correlations were found between levels of IgA-RF subclasses in SF and serum, but not in serum and saliva or in SF and saliva. Fractionation of serum, SF, and saliva from patients with RA (by high performance liquid chromatography under acidic conditions) demonstrated that both IgA subclasses with RF activity occur mainly in fractions that also contain IgM. The results of this study show that 1) IgA-RF in serum and SF is mainly of IgA1 subclass, 2) both IgA-RF subclasses are produced locally in salivary glands and in synovial tissue, 3) the production of both IgA-RF subclasses at mucosal and nonmucosal sites is independent from each other, and 4) both IgA-RF subclasses occur predominantly in polymeric form in serum, SF, and saliva in RA patients.

Arthritis, Rheumatoid↗
PubMed1991

Measurement of synovial inflammation in rheumatoid arthritis with technetium 99m labelled human polyclonal immunoglobulin G.

The ability of technetium 99m labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in patients with rheumatoid arthritis (RA). Eight patients with clinically active synovitis were injected with 350 MBq 99mTc-IgG, and imaging took place 4 h later. This resulted in excellent images of inflamed synovium. Significant correlations were observed between individual joint uptake on the scan and scores for joint pain (n = 316, p less than 0.001), joint swelling (n = 300, p less than 0.001) or the average of pain and swelling (n = 300, p less than 0.001). These results suggest that 99mTc-IgG scintigraphy may provide an objective, non-invasive test to detect and measure synovitis.

Arthritis, Rheumatoid↗
PubMed1991

Inhibition of polymorphonuclear leukocyte-mediated endothelial cell detachment by antileukoprotease: a comparison with other proteinase inhibitors.

The role of elastase and proteinase inhibitors in polymorphonuclear leukocyte(PMN)-mediated injury to human umbilical cord venous endothelial cells (HUVEC) was investigated. Both purified human neutrophil elastase and PMN that were stimulated with serum-treated zymosan (STZ) induced detachment, but not lysis of HUVEC. PMN-, but not purified elastase-mediated detachment was enhanced by the presence of methionine, which indicates a role for reactive oxygen metabolites in PMN-mediated HUVEC detachment. Detachment of HUVEC could be inhibited by secretory leukocyte proteinase inhibitor or antileukoprotease (ALP), alpha 1-proteinase inhibitor (alpha 1-PI) and N-methoxy-succinyl-ala-ala-pro-val-chloromethyl ketone (CMK). At concentrations at which elastase-mediated detachment was maximally inhibited, ALP and CMK, but not alpha 1-PI, were also able to inhibit maximally PMN-mediated detachment. An explanation for this difference could be that the larger size of alpha 1-PI reduces the access of alpha 1-PI to the interface between the PMN and the HUVEC.

Amino Acid Chloromethyl Ketones↗
PubMed1991

No effect of misoprostol on renal function of rheumatoid patients treated with diclofenac.

Non-steroidal anti-inflammatory drugs can reversibly decrease renal function in patients with rheumatoid arthritis (RA). To test whether orally administered prostaglandins could mitigate this decrease, we studied the effect of misoprostol in 24 RA patients during treatment with diclofenac in a randomized, placebo-controlled crossover trial. At baseline, 21 patients had a creatinine clearance below 80 ml/min/1.73 m2. The two treatment phases (with either misoprostol, 600 micrograms daily, or matching placebo tablets) were separated by a washout phase in which diclofenac (150 mg daily) was continued. After treatment with misoprostol/diclofenac the glomerular filtration rate was 72 +/- 5 ml/min (mean +/- standard error), and the effective renal plasma flow was 295 +/- 21 ml/min. After treatment with placebo/diclofenac, the corresponding values were 71 +/- 5 ml/min and 296 +/- 21 ml/min, respectively. We concluded that misoprostol has no effect on the renal function of RA patients treated with diclofenac.

Adult↗
PubMed1991

Interleukin-6 activity in paired samples of synovial fluid. Correlation of synovial fluid interleukin-6 levels with clinical and laboratory parameters of inflammation.

Paired synovial fluid (SF) samples obtained from the knees of 12 arthritis patients were studied to establish a relation between parameters of local inflammatory activity and SF interleukin-6 (IL-6) levels. Local disease activity was scored using joint temperature, swelling and pain as clinical parameters of inflammation. SF samples were assayed for laboratory parameters of inflammation such as leucocyte content, the percentage polymorphonuclear cells, the pH, and for immunoglobulin levels (IgG, IgM). SF IL-6 concentrations were determined using the B9-bioassay. Within individual patients the local activity of inflammation as measured using clinical parameters was found to be related to the local SF IL-6 level. When considering the total group of patients, a correlation (P less than 0.001) was found between the clinical parameters of local inflammation and the SF IL-6 levels. Furthermore, IL-6 levels were found to correlate with leucocyte counts (P less than 0.02), the percentage of polymorphonuclear cells (P less than 0.10), the pH value (P less than 0.01), but not with SF IgM and IgG concentrations.

Adult↗
PubMed1991

Lack of T cell oligoclonality in enzyme-digested synovial tissue and in synovial fluid in most patients with rheumatoid arthritis.

The dominant presence of specific T-cell populations in the rheumatoid joint as detected by Southern blot analysis of T cell receptor (TCR) gene rearrangements would indicate local antigen recognition and T cell proliferation. We therefore studied TCR beta chain gene rearrangements using a C beta 2 probe in paired samples of T cell populations from synovial tissue and peripheral blood (n = 6) as well as synovial fluid (n = 16) and peripheral blood (n = 18) of patients with rheumatoid arthritis (RA). Peripheral blood mononuclear cells from healthy donors (n = 7) served as a control. T cells were studied directly after isolation or after non-specific expansion with OKT3 monoclonal antibody (MoAb) and T cell growth factor (TCGF). DNA samples were digested with EcoRI and HindIII to detect rearrangements to C beta 1 and C beta 2, respectively. Extra bands were detected in all EcoRI-digested DNA samples prepared from both freshly isolated and non-specifically expanded T cell populations of patients and healthy donors, possibly representing 'common' (V-) D-J rearrangements. Dominant rearrangements were found in only two out of 16 synovial fluid T cell populations (one freshly isolated and one expanded) and not in peripheral blood or synovial tissue derived T cell populations. No extra bands were detected in HindIII-digested DNA samples. To investigate the effect of in vitro culture techniques on rearrangement patterns we studied DNA samples prepared from synovial tissue T cells obtained both by outgrowth from tissue with TCGF or by enzyme digestion and subsequent expansion either with TCGF or with OKT3 MoAb and TCGF. Whereas the latter T cell population yielded 'common' rearrangements, the former T cell populations yielded different dominant rearrangements. These data indicate that oligoclonality of the T cell populations in synovial tissue and synovial fluid of patients with RA is a rare event. The data also show the influence of in vitro culture techniques on the result of TCR gene rearrangement analysis.

Adult↗
PubMed1991

Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE).

IgG anti-endothelial antibodies (AEA), as measured by ELISA or immunoblotting technique could be detected in serum samples of 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA titres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endothelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE.

Antibodies, Anti-Idiotypic↗
PubMed1991

Uptake and degradation of soluble aggregates of IgG by monocytes of patients with rheumatoid arthritis: relation to disease activity.

Monocytes from patients with rheumatoid arthritis (RA) and rheumatoid vasculitis have a diminished ability to degrade soluble complexes of aggregated IgG in the absence (mediated by Fc receptors) as well as in the presence of complement (C) (mediated by (Fc + C) receptors). To investigate whether a relation exists between the receptor mediated degradation of aggregated IgG by adherent monocytes and disease activity a longitudinal study was performed in 79 patients with RA and rheumatoid vasculitis over a period of 16 months. Adherent monocytes were incubated in vitro with 125I labelled IgG aggregates of restricted size in the absence or presence of fresh serum and the percentage of catabolised IgG aggregates was measured. Cross sectionally the degradation of aggregated IgG by monocytes, mediated by Fc and (Fc + C) receptors, correlated significantly with disease activity as scored by the Ritchie articular index, the presence of extra-articular features, and circulating immune complexes. A high number of Fc receptors on monocytes correlated with diminished degradation, whereas high numbers of complement receptors 1 and 3 correlated with enhanced degradation of aggregated IgG mediated by both Fc and (Fc + C) receptors. The degradation of aggregated IgG by monocytes did not correlate with disease activity in individual patients followed up longitudinally. When patient groups were formed according to the results of longitudinal studies, however, degradation of aggregated IgG mediated by Fc and (Fc + C) receptors was significantly decreased in patients with rheumatoid vasculitis and in patients with active RA in comparison with patients with inactive RA and healthy controls. Patients with active RA and rheumatoid vasculitis also expressed significantly more Fc receptors and less complement receptors on the monocytes than patients with inactive RA. Drug treatment did not correlate with receptor expression or the degradation of aggregated IgG by monocytes either in cross sectional or longitudinal studies. It is concluded that in RA disease activity is related to receptor expression and the degradation of soluble immune aggregates by monocytes.

Adult↗
PubMed1991

Effect of monomeric immunoglobulin G (IgG) on the clearance of soluble aggregates of IgG in man.

Serum concentrations of IgG may influence Fc receptor-mediated clearance of immune complexes. For instance, when 123I-labeled aggregates of human IgG (123I-AIgG), used as a model for soluble immune complexes, are administered to patients with systemic lupus erythematosus (SLE), there is an inverse correlation between the serum concentrations of IgG and the clearance and volume of distribution in steady state (Vss) of 123I-AIgG. To answer the question whether IgG has a direct effect on the clearance of immune complexes, we measured the elimination of 123I-AIgG in eight patients with hypogammaglobulinemia, before and after substitution with intravenous gammaglobulin (IVIG). As expected, raising IgG concentrations in these patients (by 6 g/l) caused a significant decrease of the Vss of 123I-AIgG. However, clearance of 123I-AIgG remained unchanged by IVIG. Thus, the results of this study offer no experimental evidence that raising concentrations of IgG influences the clearance of soluble immune complexes.

Adult↗
PubMed1991

Prednisone plus azathioprine treatment in patients with rheumatoid arthritis complicated by vasculitis.

The therapeutic effect of prednisone combined with azathioprine was studied in 28 patients with rheumatoid vasculitis. Nine patients with severe systemic vasculitis were treated initially with 60 mg of prednisone and 2 mg/kg of body weight of azathioprine daily. Clinical signs of vasculitis decreased in all patients. Nineteen patients with only cutaneous vasculitis entered a randomized controlled study comparing prednisone plus azathioprine treatment vs continuation of various conventional antirheumatic drugs. Although measures of both vasculitis and arthritis activity improved to a greater degree in the patients treated with prednisone plus azathioprine in the first 3 months of therapy, no significant differences between the results of the two treatments were observed at the end of the follow-up period. Prednisone plus azathioprine treatment was associated with a low incidence of relapse of vasculitis, few serious complications, and a relatively low mortality. We conclude that the combination of prednisone and azathioprine is effective in the treatment of severe systemic rheumatoid vasculitis; rheumatoid vasculitis with only cutaneous manifestations has a relatively good prognosis, and there is probably no indication for therapy specifically directed at the vasculitic process.

Aged↗
PubMed1990

High antigen reactivity in mononuclear cells from sites of chronic inflammation.

Antigen-specific in-vitro responses of mononuclear cells from synovial fluid and peripheral blood of patients with rheumatoid arthritis were compared with those of mononuclear cells from pleural exudate and peripheral blood of non-rheumatoid-arthritis patients with chronic pleuritis not caused by tuberculosis. The antigens tested were an acetone-precipitable fraction of Mycobacterium tuberculosis (AP-Mt), an Escherichia coli lysate containing the 65 kD heat-shock protein of M bovis BCG (65 kD/E coli), the M bovis heat-shock protein alone (65 kD), and E coli alone. The mean proliferative responses to AP-Mt were higher in synovial-fluid than in peripheral-blood mononuclear cells in rheumatoid arthritis patients (mean [SEM] stimulation index 10.5 [3.1] vs 2.6 [0.9]) and in pleural-exudate than in peripheral-blood mononuclear cells in the pleuritic patients (7.5 [1.7] vs 3.5 [2.0]). The same pattern was seen for the other three antigens. Only 1 of 26 synovial-fluid mononuclear cell samples from rheumatoid arthritis patients showed a positive response (stimulation index 3 or more) to 65 kD compared with 5 of 22 pleural-exudate mononuclear cell samples, so 65 kD seems not to be the major antigen recognised by synovial-fluid T cells in rheumatoid arthritis. Enhanced reactivity against mycobacterial and other bacterial antigens is not restricted to mononuclear cells from chronically inflamed joints but seems to be a common feature of chronic inflammation.

Antigens, Bacterial↗
PubMed1990

Subclinical renal dysfunction in rheumatoid arthritis.

We studied renal function in 35 patients with chronic, seropositive rheumatoid arthritis (RA), of whom 7 had vasculitis, 10 had hypergammaglobulinemia, and 18 had neither of these 2 conditions. Findings included a decreased glomerular filtration rate in 8 patients, (micro)proteinuria in 11, a defective urine concentration in 10, and increased urinary tubular enzyme levels in 15. These results indicate that subclinical renal dysfunction is common in patients with chronic, seropositive RA. In addition, vasculitis and hypergammaglobulinemia were not identified as risk factors for renal dysfunction in the RA patients studied.

Arthritis, Rheumatoid↗
PubMed1990

IgG and IgA antibodies to the collagen-like region of C1q in rheumatoid vasculitis.

We investigated the presence of IgG and IgA antibodies to C1q in serum samples from 80 patients with rheumatoid arthritis (RA), 31 patients with rheumatoid vasculitis, and 80 healthy controls. IgG and IgA antibodies to C1q, as measured by enzyme-linked immunosorbent assay, were found in less than 5% of the sera from RA patients and from healthy controls. In contrast, IgG and IgA antibodies to C1q were found in 29% and 61%, respectively, of the sera from patients with rheumatoid vasculitis. The occurrence of IgA antibodies to C1q has not been previously demonstrated. These results also demonstrate that IgG antibodies to C1q do not occur exclusively in systemic lupus erythematosus patients: Sera of patients with rheumatoid vasculitis frequently contain IgG or IgA antibodies to C1q, which contribute to immune complex formation.

Adult↗