Prediction of glomerular filtration rate in patients with rheumatoid arthritis: satisfactory performance of Cockroft formula.
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Adult↗
Biomedical subjects
F C Breedveld
Publications and source records attributed to F C Breedveld.
Towards T cell vaccination in rheumatoid arthritis.
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Animals↗
Hypersensitivity pneumonitis during minocycline treatment.
A patient is reported who developed dyspnoea, fever, pleuritic chest pain and a non-productive cough following treatment with minocycline for 9 days. The chest radiograph showed an interstitial pattern and there was a peripheral eosinophilia. A diagnosis of hypersensitivity pneumonitis attributable to minocycline was made. The disease responded quickly to withdrawal of the drug. This observation shows that minocycline, despite its mild toxicity profile, can give rise to serious adverse effects.
Alveolitis, Extrinsic Allergic↗
Influence of non-inherited maternal HLA antigens on occurrence of rheumatoid arthritis.
Many HLA-associated diseases occur in patients not carrying the putative predisposing antigen. The suggestion that this might be due to disease heterogeneity is not sufficiently supported by available data. We hypothesise that HLA-DR4-associated genetic susceptibility to rheumatoid arthritis is due to an effect of DR4 on T-cell receptor repertoire expression and that the presence of antigen in the mother is capable of producing this effect in her children, even when DR4 is not inherited by them. To investigate this possibility we HLA typed 94 rheumatoid arthritis patients and their parents and 86 control families. An increased frequency, compared with controls, of non-inherited maternal HLA-DR4 was found predominantly in the mothers of DR4-negative patients. Unexpectedly, we also found an increased frequency of non-inherited maternal HLA-DR6 and a decreased frequency of non-inherited maternal HLA-DR3 in the mothers of DR4-positive patients. The results of our analyses are consistent with our hypothesis.
Arthritis, Rheumatoid↗
Susceptibility to relapsing polychondritis is associated with HLA-DR4.
OBJECTIVE: To determine the frequency of HLA class II antigens in Caucasian central European patients with relapsing polychondritis (RP). METHODS: HLA class I, DR, and DQ specificities were identified in 41 patients with RP, and the frequencies were compared with those in 204 healthy, unrelated control subjects. HLA typing was performed using the standard complement-dependent microcytotoxicity assay. HLA-DR genotyping of 12 DR4-positive RP patients and 57 controls was performed by allele-specific oligonucleotide probing after amplification of genomic DNA by polymerase chain reaction. RESULTS: A significant increase in DR4 antigen frequency was found in the patients (56.1%) as compared with that in healthy controls (25.5%) (Pcorr < 0.001). Genotyping of DR4-positive patients and controls revealed no predominance of any DR4 subtype. CONCLUSION: There are important clinical similarities and overlaps between RP and rheumatoid arthritis (RA). In RA, the association with DR4 has been well established. Our findings show that although there is a DR4 association with RP, the situation is sufficiently distinct from that of RA to imply considerable differences in pathogenesis of the two conditions.
Alleles↗
Chimeric CD4 monoclonal antibody cM-T412 as a therapeutic approach to rheumatoid arthritis.
OBJECTIVE: To investigate the effects of chimeric CD4 monoclonal antibody cM-T412 treatment in patients with rheumatoid arthritis (RA). METHODS: Thirty-two RA patients received daily doses of 10, 50, or 100 mg of cM-T412 intravenously for 7 days. RESULTS: There was a sustained decrease in the number of CD4+ T lymphocytes in all patients. Those who received 50 mg and 100 mg of the antibody experienced significant reductions in disease activity. CONCLUSION: Treatment with cM-T412 appears to have a dose-dependent beneficial effect in RA patients. The clinical effects of cM-T412 are independent of the depressed numbers of circulating CD4+ T cells.
Adult↗
Role of liver endothelial and Kupffer cells in clearance of human C1q in rats.
In the present study the contribution of rat liver endothelial cells (EC) and Kupffer cells (KC) in the clearance of human (hu) C1q in rats was investigated. In untreated rats and rats depleted from KC the clearance kinetics and the tissue distribution of hu C1q were measured. In untreated rats, the clearance of hu C1q occurred in a monophasic manner with a half-life of 66 +/- 26.7 min. The clearance of hu C1q in KC-depleted rats was delayed significantly (p < 0.001) and occurred with a half-life of 217 +/- 78.8 min. Fifteen min after injection, 11 +/- 3.5% of hu C1q was found in the liver of untreated rats and 8 +/- 1.4% was found in the liver of KC-depleted rats. The percentage non-trichloroacetic acid precipitable activity in the circulation, as a measure for degradation of C1q, reached a level of 11.6 +/- 5.6% at 240 min in untreated rats compared with 4.6 +/- 5.8% in KC-depleted rats. Double immunofluorescence staining 5 min after administration of C1q in untreated rats, revealed that C1q was associated with KC and EC in the liver. Fifteen minutes after i.v. injection of hu C1q, there was an uptake of C1q in the hepatocytes. In KC-depleted rats, 5 min after administration of hu C1q, C1q was bound to the EC. Fifteen minutes after injection, C1q was also found in the hepatocytes. Electron microscopical studies revealed that C1q binds to EC, and that it is internalized in the hepatocytes and KC. The clearance of hu C1q in untreated rats was inhibited by preadministration of high concentrations of bovine C1q. These data show that rats depleted from KC are able to bind, internalize and degrade C1q, and that EC may play a role in the handling of C1q and C1q bound to immune complexes.
Animals↗
Detection of intracellular interferon-gamma by light microscopy using an immunoperoxidase technique: correlation with the corresponding mRNA and protein product.
Identifying individual cytokine-producing cells may help to acquire insight into immunological processes. This study was designed to adapt a technique for the detection of individual cytokine-producing cells from an immunofluorescence to an immunoperoxidase staining procedure. The production of interferon-gamma (IFN-gamma) by anti-CD3-activated cloned human T cells was used as a model system. After the conditions for the staining procedure were optimized, the immunoperoxidase technique was slightly more sensitive than the immunofluorescence technique. The intracellular staining for IFN-gamma was preceded or paralleled by IFN-gamma mRNA production and followed by accumulation of IFN-gamma in the supernatant. It is concluded that intracellular IFN-gamma can easily be detected using an immunoperoxidase procedure. This procedure is highly sensitive and allows quantification of the production of multiple cytokines by counting the percentage of positively staining cells.
Cytokines↗
Activated synovial T cell clones from a patient with rheumatoid arthritis induce proliferation of autologous peripheral blood-derived T cells.
In order to investigate cellular interactions involved in the development of human autoimmune disease, a synovial fluid-derived T cell clone reactive with mycobacterial antigens, termed k38, was employed as a stimulus for autologous peripheral blood mononuclear cells (PBMC). Stimulator cells were used either activated with immobilized OKT3 mAb or in a resting state. Activated k38 cells triggered PBMC to proliferate. A T cell line prepared by coculturing autologous PBMC with irradiated activated k38 cells proliferated upon stimulation with activated k38 cells in the presence of PBMC as a source of accessory cells, as did T cell clones that were subsequently isolated from this line. Blocking studies revealed that proliferation of the anti-k38 line and anti-k38 clones in response to stimulation with clone k38 could be inhibited by monoclonal antibodies against a variety of cellular determinants including HLA class I and LFA-1 beta. It was demonstrated that the antigen reactivity of clone k38 was modulated by the presence of anti-k38 clones. These data provide a model for understanding the cellular interactions that may take place in vivo in the evolution of the chronic synovial inflammatory process.
Antibodies, Monoclonal↗
Rheumatoid factor isotypes in serum and salivary fluid of patients with primary Sjögren's syndrome.
Salivary fluid and serum levels of immunoglobulin and rheumatoid factor (RF) isotypes were measured in patients with primary Sjögren's syndrome (SS) as well as in patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) in order to investigate the site of RF production in primary SS and to determine the diagnostic value of determination of salivary fluid levels of RF. Increased salivary fluid levels of IgA-RF were found in 46% of 39 primary SS patients, 14% of 42 NON-SS patients, and in 2% of 41 healthy controls. Salivary fluid levels of other RF isotypes were not increased in the patient groups. The frequency of elevated titers of IgA-, IgG-, and IgM-RF in serum of primary SS patients was 51, 7, and 59%, respectively. The levels of IgA, IgG, and IgM in salivary fluid of primary SS patients were increased in 36, 31, and 23%, respectively. Comparison of RF levels in samples of serum and saliva from primary SS patients after correction for immunoglobulin levels indicated local production of IgA-RF in salivary glands. Significant positive correlations were found between IgA-RF levels in serum and saliva but not between the levels of immunoglobulin isotypes in the two compartments. The results of this study show that (1) increased levels of IgA-, but not IgG- and IgM-RF occur in saliva of primary SS patients; (2) IgA-RF is locally produced in the salivary glands; (3) the stimuli for IgA-RF production in the systemic and secretory compartment may be similar; and (4) measurement of both IgA- and IgM-RF in serum may be used as adjunctive diagnostic procedure for primary SS.
Adult↗
The relationship between serum titers of autoantibodies to C1q and age in the general population and in patients with systemic lupus erythematosus.
The aim of the present study was to assess the relationship between age and titers of autoantibodies to C1q (C1qAb) in individuals randomly selected out of the general population and in systemic lupus erythematosus (SLE) patients. Serum samples of 659 randomly selected individuals and 169 SLE patients were divided into 6 age groups from 20 to 79 years. IgG and IgA C1qAb titers were measured by ELISA. The highest titers of IgG and IgA C1qAb in sera of randomly selected individuals were found in the oldest age groups. In serum of SLE patients the highest titers of IgG C1qAb were found in the youngest age groups, whereas IgA C1qAb titers did not change with aging. It is concluded that the distribution pattern of IgG and IgA C1qAb titers in serum of individuals randomly selected out of the general population is similar to that of other autoantibodies. The increased titers of IgG C1qAb in serum of young patients with SLE suggest a role of these antibodies in the pathogenesis of the disease.
Adolescent↗
Effects of inoculation with attenuated autologous T cells in patients with rheumatoid arthritis.
Injection of attenuated autoimmune T cells, T cell vaccination, has been used successfully in the prevention and treatment of experimental animal autoimmune disease. In order to determine whether such a procedure might be applied in rheumatoid arthritis (RA), a phase I study was conducted in thirteen RA patients with a mean disease duration of 12.8 years. All patients received a subcutaneous injection of attenuated autologous T lymphocytes from a CD4 positive clone (n = 4) or line (n = 9) isolated from synovial tissue (n = 3) or synovial fluid (n = 10). No toxic side effects were observed. On the average the patients showed a slight decrease in disease activity which was most marked at 8 weeks after the injection. Specific immune reactivity against the injected T cells was not detected, with the possible exception of one patient who was vaccinated with a clone selected in vitro with antigen and whose disease had begun one year earlier. In this patient a clear decrease in disease activity occurred, which was associated with a decrease in mitogen-induced proliferation of her peripheral blood mononuclear cells and in titres of serum rheumatoid factors. The results of this study show that inoculation of RA patients with autologous T cells is technically feasible and non-toxic, and may be associated with clinical and immunological effects. The data suggest that the potential of T cell vaccination should be further explored in diseases with defined antigen reactivity.
Adult↗
Anti-lactoferrin antibodies in patients with rheumatoid arthritis with vasculitis.
Anti-lactoferrin antibodies (anti-LF Ab) are more frequently found in patients with rheumatoid arthritis (RA) complicated by vasculitis when compared to patients with uncomplicated RA. Therefore the detection of anti-LF Ab in serum of patients with RA may be useful in the diagnosis of vasculitis in RA patients.
Antibodies, Antineutrophil Cytoplasmic↗
Levels of soluble receptors for tumor necrosis factor type I and type II in paired synovial fluids of arthritis patients.
The objective of this study was to determine whether levels of soluble receptors for tumor necrosis factor type I and type II (sTNF-RI and sTNF-RII) as measured in paired synovial fluids (SF) of arthritis patients are associated with clinical or laboratory parameters of local inflammation. sTNF-RI and -RII were measured by ELISA. We found that sTNF-RI and -RII did not correlate with activity of local inflammation. sTNF-RI levels correlated with sTNF-RII concentrations. We concluded that sTNF-RI and -II did not represent markers for local disease activity in arthritis patients.
Adult↗
The "shrinking lung syndrome" in SLE, treatment with theophylline.
We report on a patient with systemic lupus erythematosus who developed a shrinking lung syndrome. The dyspnoea of the patient and the results of pulmonary function tests significantly improved during treatment with theophylline 750 mg daily. This is the first report of a successful treatment of the shrinking lung syndrome with theophylline.
Dyspnea↗
T-cell receptor V-gene usage in synovial fluid lymphocytes of patients with chronic arthritis.
In this study we analyzed the usage frequencies of the TCR V-gene segments by alpha beta+ T cells present in synovial fluid of 17 patients with chronic arthritis, including rheumatoid arthritis. The results of this study, obtained from semiquantitative PCR analyses, showed that in all patients most of the TCR V alpha- and V beta-gene segments could be detected both in fresh PBMCs and in fresh SFMCs. The relative frequencies of use of these V-region genes were variable between the different patients. Although there was some skewing of increased usage frequencies of particular TCR V alpha and V beta genes among SFMC-derived TCRs when compared with PBMCs, we could not correlate such increased TCR V-gene usage with the inflammation in the joints as a disease-specific marker.
Adult↗
Silicone breast prostheses and rheumatic disorders.
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Breast↗
Rheumatoid arthritis in a population of persons aged 85 years and over.
A Dutch urban population of 977 persons aged 85 years and over was examined for the presence of rheumatoid arthritis (RA). Prevalence rates for definite RA, past polyarthritis with joint deformation and past polyarthritis without joint deformation were 0.3%, 0.3% and 0.7%, respectively. The polyarthritis patients did not differ from age-matched controls with respect to crude scores of physical disability, the presence of serum rheumatoid factor or the presence of HLA-DR4. Although these data should be interpreted with caution because of the small patient groups, we conclude that in persons aged 85 years and over the prevalence of RA is low, and the disease is relatively mild.
Age Factors↗