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F C Breedveld

Publications and source records attributed to F C Breedveld.

At least 163 records · Page 9Linked to original sources
PubMed1999

The levels of soluble granzyme A and B are elevated in plasma and synovial fluid of patients with rheumatoid arthritis (RA).

Cytotoxic cells possess specialized granules which contain perforin and a group of serine proteinases termed granzymes. Granzyme-positive cells have been identified in synovial fluid and tissue of patients with RA, where they may play an important role as mediators of granule-mediated apoptosis, extracellular proteolysis, and cytokine induction. The aim here was to define further the involvement of cytotoxic cells in RA. Plasma and synovial fluid samples from the knee joint were obtained from 31 RA patients. The disease controls included 20 osteoarthritis (OA) patients and 10 reactive arthritis (ReA) patients. A recently developed capture ELISA was used to detect soluble granzymes A and B in all patients. Compared with OA and ReA disease controls, markedly increased levels of soluble granzymes A and B were detected in both plasma and synovial fluid of RA patients (P < 0.00001). When values for soluble granzymes A and B in plasma and synovial fluid were used simultaneously as independent variables, logistic regression analysis indicated that a diagnosis of RA could be predicted correctly in 84% of the RA patients and a diagnosis of non-RA in 90% of the controls. The markedly elevated levels of soluble granzymes A and B in plasma and synovial fluid of RA patients strongly suggest that cytotoxic cells are active participants in the pathogenesis of RA. Moreover, the results suggest that measurement of granzymes may assist the laboratory evaluation of patients with arthritis. Larger studies in patients with early disease may clarify the role of this test system in differential diagnosis.

Adult↗
PubMed1999

Haplotype analysis of three polymorphisms of the COL2A1 gene and associations with generalised radiological osteoarthritis.

It was investigated whether radiographic osteoarthritis (ROA) is associated with specific haplotypes of the COL2A1 gene. Radiographs of knees, hips, hands, and spine were scored for the presence of ROA in subjects of 55-70 years from a population-based cohort study, the Rotterdam study. Cases had ROA in 3 or more joint groups; controls, from the same population, had ROA in less than 3 joint groups. Allele frequencies of 3 dimorphisms (HaeIII, HindIII, MaeII) and a VNTR polymorphism of the COL2A1 gene were determined. The VNTR allele 14R2 and the HindIII polymorphism showed a significant association. Haplotype analysis of the HaeIII, HindIII and VNTR polymorphisms showed that a specific haplotype (1-2-14R2) is strongly associated with ROA in 3 or more joint groups (OR = 5.3, 95% CI 2.3-12.7). Our results suggest that a specific haplotype of the COL2A1 locus may predispose to generalised ROA.

Aged↗
PubMed1999

Investigational treatments in rheumatoid arthritis.

The active search for new treatment modalities of established rheumatoid arthritis have created a dynamic period for rheumatology. Both promising pharmaceutical products and targeted interventions with products of the biotechnology industry are being developed. Leflunomide and the selective blockade of the cytokine tumour necrosis factor (TNF) have recently been registered in several countries and others will follow. Like all new therapeutic strategies much remains to be learned about the optimal use of these therapies and their possible limitations. The success of these interventions have shown that a complex disease such as rheumatoid arthritis that is refractory to conventional treatment can be modulated by new therapeutic strategies. This experience has also resulted in further searches for new drugs that influence those pathogenetic pathways affected by the interventions found to be effective.

Animals↗
PubMed1999

Childhood-onset Systemic Lupus Erythematosus: clinical presentation and prognosis in 31 patients.

OBJECTIVE: To determine the clinical features at onset, the disease course, and prognostic factors in children with SLE. METHODS: The medical records of 31 patients with childhood-onset SLE were reviewed. Signs and symptoms at onset and during the course of the disease were documented as well as survival and SLICC/ACR damage index. The disease course was compared to 135 consecutive adult-onset SLE patients. RESULTS: Childhood-onset SLE most frequently presented with fatigue, arthritis, fever, weight loss, and malar rash. During follow-up, the frequency of the presence of malar rash, anemia, leukocytopenia, and anti-dsDNA antibodies was significantly higher in childhood-onset than in adult-onset patients. Mean SLICC/ACR damage index was 2.6 after 4.7 years of follow-up. The presence of arthritis, anemia, and seizures at the onset of disease resulted in a 2.6 to 3.9 times higher chance of a severe disease course. CONCLUSION: Patients with childhood-onset SLE suffer from substantial morbidity. Arthritis, anemia, and seizures at onset may be indicators of poor prognosis.

Adolescent↗
PubMed1999

The influence of a partially HLA-matched blood transfusion on the disease activity of rheumatoid arthritis.

OBJECTIVE: Based on the immunosuppressive effects of blood transfusions in organ transplantation, we determined the effect of a blood transfusion on disease activity of rheumatoid arthritis (RA). METHOD: In this double-blind pilot study, 40 patients with active RA were randomly assigned to receive a HLA-DRB1-matched blood transfusion (n = 30) or placebo (n = 10). Disease activity was scored according to the American College of Rheumatology response criteria during 6 months of follow-up. RESULTS: After 1 month and 6 months, respectively, 6 and 16% of patients fulfilled the response criteria in the blood transfusion group compared to none and 30%, respectively, in the placebo group. Following correction for the increase in haemoglobin levels, a majority of the response parameters in the blood transfusion group showed significant improvement compared to the placebo group. CONCLUSION: A DRB1-matched blood transfusion shows improvement of symptoms in several RA patients. Additional studies are required to identify blood transfusion regimens that enhance the potential for therapeutic responses.

Adult↗
PubMed1999

Immunohistological analysis of synovial tissue for differential diagnosis in early arthritis.

OBJECTIVE: An early diagnosis in patients presenting with arthritis is important to provide information about prognosis and to initiate treatment. The objective of this study was to determine which markers applied in immunohistological analysis of synovial tissue (ST) specimens could be used to differentiate rheumatoid arthritis (RA) from other forms of arthritis. METHODS: Synovial biopsies were obtained by blind needle techniques from 95 patients with early arthritis. After follow-up of at least 2 yr to verify the diagnosis, the patients could be classified as follows: RA (n=36), undifferentiated arthritis (UA; n=21), osteoarthritis (OA; n=17), reactive arthritis (ReA; n=10), ankylosing spondylitis (AS; n=3), psoriatic arthritis (PsA; n=2) and crystal-induced arthritis (CA; n=6). ST sections were analysed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD22 (B cells), CD38 (plasma cells), CD68 (macrophages) and CD55 (fibroblast-like synoviocytes). RESULTS: Logistic regression analysis revealed that the higher scores for the numbers of CD38+ plasma cells and CD22+ B cells in RA were the best discriminating markers comparing RA to non-RA patients (CD38: P=0.0001; CD22: P<0.05). Polychotomous regression analysis comparing three diagnostic categories (1: RA; 2: UA, ReA, AS and PsA; 3: OA and CA) also identified the score for the number of CD38+ plasma cells (P<0.0001) as well as the numbers of CD68+ macrophages in the synovial sublining (P=0.05) as discriminating markers. CONCLUSION: The results suggest that immunohistochemical analysis of ST specimens from early arthritis patients can be used to differentiate RA from non-RA patients. The numbers of plasma cells, B cells and macrophages are especially increased in ST of patients with RA. Future studies in early arthritis patients with clinical features which do not allow an immediate confident diagnosis may clarify the role of this test system in differential diagnosis.

Adult↗
PubMed1999

Cyclosporin A therapy in rheumatoid arthritis: only strict application of the guidelines for safe use can prevent irreversible renal function loss.

OBJECTIVES: To investigate (1) whether the increase in serum creatinine observed during cyclosporin A (CsA) therapy was reversible in a group of patients with rheumatoid arthritis (RA) treated before the current guidelines for safe use in RA were developed and (2) whether the application of these guidelines prevents serum creatinine increases in the long term. PATIENTS AND METHODS: Eighty-three RA patients who had started low-dose CsA therapy between September 1990 and October 1992, and who were treated according to guidelines that allowed a 50% rise in serum creatinine, were tested for serum creatinine levels in December 1995 if they had discontinued CsA for at least 3 months. Predictors for irreversibility of renal function were determined by using multiple regression analysis. RESULTS: The mean level of serum creatinine gradually increased from 69+/-14 (mean+/-S.D.) micromol/l when starting CsA therapy to 88+/-23 micromol/l (28% above baseline) at the moment of CsA discontinuation, and had decreased to 80+/-17 micromol/l (16% above baseline) at follow-up, 35+/-14 months after drug discontinuation. During CsA therapy, the mean level of serum creatinine had increased to 82+/-19 micromol/l (26% above baseline) at 6 months and to 87+/-22 micromol/1 (39% above baseline) at 42 months. The mean CsA dose had decreased from 3.1+/-0.9 mg/kg/day at 6 months to 1.9+/-0.8 mg/kg/day at 42 months. The absolute number of months that serum creatinine levels were > 30% above baseline was an independent predictor for a persistent increase of the serum creatinine after CsA discontinuation. More than 2 months with a serum creatinine increase of > or = 30% resulted in a higher percentage irreversible increase than for less than 2 months with a > or = 30% increase: 27 and 6%, respectively (P < 0.0001). CONCLUSION: Long-term low-dose CsA administration in RA patients was associated with an increase in serum creatinine which was partially irreversible after drug discontinuation. The increase in serum creatinine was completely reversible in the patient group that was treated according to the current guidelines for safe use of CsA.

Adolescent↗
PubMed1999

The effects of interferon beta treatment on arthritis.

OBJECTIVE: To determine whether interferon beta (IFN-beta) therapy might have a beneficial effect on arthritis, we evaluated the effect of IFN-beta on collagen type II-induced arthritis (CIA) in rhesus monkeys and conducted a pilot study in patients with rheumatoid arthritis (RA). METHODS: Four rhesus monkeys with CIA were treated with 10 x 10(6) U (MIU)/kg mammalian cell-derived recombinant IFN-beta (Rebif; Ares-Serono) s.c. daily for 1 week. Subsequently, 12 patients with active RA were treated for 12 weeks with purified natural fibroblast IFN-beta (Frone, Ares-Serono) s.c. 3 times weekly at the following dosages: 6 MIU (n = 4), 12 MIU (n = 4) and 18 MIU (n = 4). RESULTS: Rapid clinical improvement during IFN-beta therapy was observed in three of the four rhesus monkeys with CIA. There was also a marked decrease in serum C-reactive protein (CRP) levels with a subsequent increase after discontinuation of the treatment in all monkeys. The 10 RA patients who completed the study exhibited on average gradual improvement of tender and swollen joint counts, patient's assessment of pain, and patient's and doctor's global assessment (all P < 0.05). The health assessment questionnaire and serum CRP levels also tended to decrease, but this was not statistically significant; 40% of the patients fulfilled the ACR criteria for 20%, improvement, whereas none fulfilled the ACR criteria for 50% improvement 12 weeks after initiation of treatment. There was no clear dose response relationship. CONCLUSION: The data suggest that IFN-beta treatment has a beneficial effect on arthritis.

Adjuvants, Immunologic↗
PubMed1999

Detection of mycobacteria in joint samples from patients with arthritis using a genus-specific polymerase chain reaction and sequence analysis.

OBJECTIVE: Mycobacteria have been implicated in the pathogenesis of various forms of arthritis. The aim of this study was to examine the diagnostic potential of molecular biological techniques as well as to investigate the pathogenetic role of mycobacteria in chronic arthritis. PATIENTS AND METHODS: DNA, extracted from synovial fluid and synovial tissue samples from patients with mycobacterial septic arthritis (n = 2), seronegative spondyloarthropathies (SpA) (n = 18), undifferentiated arthritis (UA) (n = 21) and rheumatoid arthritis (RA) (n = 40), was analysed using a mycobacterial genus-specific polymerase chain reaction (PCR) applied to amplify mycobacterial DNA. Subsequently, automated sequencing was performed for speciation. Samples from patients with either non-mycobacterial septic arthritis, osteoarthritis (OA), crystal arthritis or joint trauma served as negative controls (n = 19). RESULTS: Mycobacterium tuberculosis complex and Mycobacterium marinum were detected in the two patients with mycobacterial septic arthritis. The other species identified were Mycobacterium hodleri (in one RA patient), Mycobacterium smegmatis (in one OA patient and two RA patients) and Mycobacterium austroafricanum (in one crystal arthritis patient). All other samples were negative. CONCLUSIONS: The results suggest that the mycobacterial genus-specific PCR applied on DNA extracts isolated directly from joint samples may be employed as an additional diagnostic tool in the case of clinical suspicion of a mycobacterial infection. No evidence was obtained for a pathogenetic role of mycobacteria in SpA, UA or RA.

Adolescent↗
PubMed1999

Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes.

OBJECTIVE: To investigate the association of interleukin 10 (IL10) promoter polymorphisms and neuropsychiatric manifestations of systemic lupus erythematosus (SLE). METHODS: IL10 haplotypes of 11 healthy volunteers were cloned to confirm that in the Dutch population, only the three common haplotypes (-1082/-819/-592) GCC, ACC and ATA exist. The IL10 promoter polymorphisms of 92 SLE patients and 162 healthy controls were determined. The medical records of the SLE patients were screened for the presence of neuropsychiatric involvement. RESULTS: All cloned haplotypes were either GCC, ACC or ATA. Forty two SLE patients had suffered from neuropsychiatric manifestations (NP-SLE). In NP-SLE patients, the frequency of the ATA haplotype is 30% versus 18% in the controls and 17% in the non-NP-SLE group (odds ratios 1.9, p = 0.02, and 2.1, p = 0.04, respectively), whereas the GCC haplotype frequency is lower in the NP-SLE group compared with controls and non-NP-SLE patients (40% versus 55% and 61%, odds ratios 0.6, p = 0.02 and 0.4 p = 0.006). The odds ratio for the presence of NP-SLE is inversely proportional to the number of GCC haplotypes per genotype when the NP-SLE group is compared with non-NP-SLE patients. CONCLUSIONS: The IL10 locus is associated with neuropsychiatric manifestations in SLE. This suggests that IL10 is implicated in the immunopathogenesis of neuropsychiatric manifestations in SLE.

Adult↗
PubMed1999

Predicting functional status in patients with rheumatoid arthritis.

OBJECTIVE: To determine whether coping strategies and illness perceptions would be predictive of outcome in a longitudinal study of patients with rheumatoid arthritis (RA). METHODS: A group of 71 patients with RA was examined on 2 occasions, one year apart. Multiple regressions were used to examine which of the illness perceptions and coping strategies explained variance on the outcome variables: visits to the outpatient clinic, number of hospital admissions, Health Assessment Questionnaire, pain, tiredness, the Hospital Anxiety and Depression Scale. RESULTS: Belief in adverse consequences of the disease was associated with more visits to the outpatient clinic. more tiredness, and higher anxiety scores. Less perceived control and less expression of emotion were associated with more hospital admissions. High scores on coping involving fostering reassuring thoughts were associated with more functional disability. More passive coping was associated with more functional disability and higher anxiety scores. More perceived symptoms were associated with more pain, more tiredness, and more depression. More avoidant coping was associated with more tiredness. Belief that the illness will last a long time was associated with higher anxiety scores. CONCLUSION: Our longitudinal data show that, after statistically controlling for the potential effects of intervening medical variables, coping strategies and illness perceptions contribute to health outcome in patients with RA. Implications for patient management are discussed.

Adaptation, Psychological↗
PubMed1999

Analysis of serial synovial biopsies in patients with rheumatoid arthritis: description of a control group without clinical improvement after treatment with interleukin 10 or placebo.

OBJECTIVE: Analysis of serial synovial biopsy specimens is increasingly used as an outcome measure for the evaluation of therapeutic interventions. However, observations in placebo treated groups are scarce. We describe the immunohistologic features of the synovium in placebo treated patients with RA and in those who received interleukin 10 (IL-10). METHODS: Ten patients with active RA received dosages of either placebo (n = 7) or 5 microg/kg (n = 1) or 10 microg/kg (n = 2) of recombinant human IL-10 (rhIL-10; SCH 52000, Schering-Plough, Kenilworth, NJ, USA) daily for 28 consecutive days. Synovial biopsy specimens from the knee joint were obtained by needle arthroscopy before and 4 weeks after initiation of treatment. Immunohistochemistry was performed using monoclonal antibodies specific for the following surface markers and cytokines: CD3, CD4, CD8, CD38, CD68, CD55, IL-1beta, IL-6, and tumor necrosis factor-alpha. RESULTS: No patient exhibited clinical improvement after treatment with placebo or any rhIL-10 dosage. Microscopic analysis of synovial tissue revealed no significant change in the scores for infiltration by inflammatory cells or in the scores for the expression of cytokines after treatment. CONCLUSION: Studies of serial synovial biopsies from patients treated with placebo or IL-10 revealed no changes in immunohistologic scores. This suggests that the biopsy procedure itself has no effect on the features of the synovium.

Adult↗
PubMed1999

Catastrophic manifestation of the antiphospholipid syndrome.

We describe a young woman who displayed the "malignant" variant of the antiphospholipid syndrome (APS), also known as the "catastrophic APS." Renal insufficiency, retinopathy, cerebral infarcts, bone marrow necrosis, skin ulcers, and nasal septum perforation were the result of widespread thrombotic microangiopathy. She recovered during high intensity anticoagulation.

Adolescent↗
PubMed1999

Future trends in the treatment of rheumatoid arthritis: cytokine targets.

Recently, anti-inflammatory cytokines and cytokine-blocking agents such as monoclonal antibodies, soluble receptors and receptor antagonists have been explored as therapeutic agents for patients with rheumatoid arthritis. The anti-inflammatory cytokines interleukin 10 (IL-10), which reverses the cartilage degradation induced by antigen-stimulated mononuclear cells, and IL-4, which reduces prostaglandin production by synoviocytes, are currently being tested for their clinical efficacy. Trials with the tumour necrosis factor alpha blocking agents infliximab (monoclonal antibody) and etanercept (the fusion protein of soluble tumour necrosis factor receptors linked to human immunoglobulin) have produced improvements in clinical and laboratory measures of inflammation with mild side-effects. Trials of IL-1 blockade with recombinant human IL-1 receptor antagonist produced significant improvement of clinical parameters with mild side-effects. Blockade of IL-6, the cytokine that induces biosynthesis of acute-phase proteins, has been attempted with i.v. injections of anti-IL-6 monoclonal antibodies with improvement in clinical variables as well as reduced acute-phase proteins.

Arthritis, Rheumatoid↗
PubMed1998

Analysis of the cellular infiltrates and expression of cytokines in synovial tissue from patients with rheumatoid arthritis and reactive arthritis.

The cellular infiltrates and cytokine patterns in synovial tissue (ST) from patients with rheumatoid arthritis (RA) and reactive arthritis (ReA) were compared in order to determine the mechanisms responsible for the chronic and destructive course of RA. Since the results could be influenced by differences in disease duration, ST was studied from patients in both early and late stages of the disease. Ten patients had early RA (< 1 year), ten long-standing RA (> 1 year), six early ReA (< 1 year), and five long-standing ReA (> 1 year). Histological analysis demonstrated that the scores for infiltration by lymphocytes and plasma cells, and the scores for inflammation, were significantly higher in RA than in ReA. Immunolabelling studies showed that in particular, the scores for infiltration by CD38+ plasma cells, granzyme B+ cells, and interferon-gamma (IFN gamma)+ cells were significantly higher in RA than in ReA. The results were independent of the disease duration. The increased number of lymphocytes, plasma cells, and granzyme B+ cells in rheumatoid synovial tissue supports the paradigm that RA is the result of specific immune recognition in the joint and that granzyme B+ cells play an important role in joint destruction.

Adolescent↗