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Biomedical subjects

F C Breedveld

Publications and source records attributed to F C Breedveld.

At least 199 records · Page 11Linked to original sources
PubMed1998

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis.

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.

Adolescent↗
PubMed1998

The diagnostic value of perivascular infiltrates in muscle biopsy specimens for the assessment of rheumatoid vasculitis.

OBJECTIVE: To determine the diagnostic value of perivascular infiltrates (PVI) in randomly obtained muscle biopsy specimens for the assessment of rheumatoid vasculitis (RV). METHODS: The number and size of PVIs, defined as the presence of mononuclear or polymorphonuclear cells around > or = 50% of the circumference of a vessel wall, as well as the presence of fibrinoid necrosis were determined in frozen sections of muscle samples of RV patients with histologically confirmed vasculitis in fixed muscle tissue (n = 12). The findings were compared with those observed in frozen sections of muscle biopsy specimens of rheumatoid arthritis (RA) patients not suspected of vasculitis (n = 14) and patients with osteoarthritis (OA) (n = 11). The presence of PVIs and of fibrinoid necrosis were sought in four frozen sections of the muscle biopsy specimen. RESULTS: PVIs were observed in 75% of the RV patients, which was significantly (p < 0.05) higher than the frequency found in RA (14%) or OA (18%) patients. PVIs with > or = three cell layers were found in 67% of the RV patients and in none of the RA and OA patients (p < 0.05). Fibrinoid necrosis was found in least one of four frozen section in 33% of the RV patients. There was a good intra-observer and inter-observer concordance on the presence of fibrinoid necrosis and of PVIs with > or = three cell layers. CONCLUSIONS: The assessment of PVIs with > or = three cell layers in a muscle biopsy specimen is a specific and reliable test in discriminating RV from RA without vasculitis. The demonstration in muscle of PVIs with > or = three cell layers is more sensitive than that of fibrinoid necrosis in the diagnosis of RV.

Aged↗
PubMed1998

Influence of HLA-class II incompatibility between mother and fetus on the development and course of rheumatoid arthritis of the mother.

OBJECTIVE: To assess the relation between the course of rheumatoid arthritis (RA) during pregnancy or the onset of RA postpartum and DRB1, DQA1, and DQB1 incompatibilities between mother and child. METHODS: In 45 pregnancies of 33 RA patients the course of RA was related to the number of class II incompatibilities. Furthermore class II incompatibilities in 16 pregnancies followed by RA onset were compared with those in 87 control pregnancies. RESULTS: The risk of a favourable compared with an unfavourable course was 0.95, 2.67, and 2.38 in case of DRB1, DQA1, and DQB1 incompatibility respectively. DQA1 and DQB1 incompatibilities were seen more often in the 10 pregnancies followed by RA onset within three months than in control pregnancies (OR 8.02, 95% CI 0.97, 66.06 and OR 8.79 95% CI 1.07, 72.46 respectively). CONCLUSIONS: DQA1 and DQB1 incompatibility between mother and child seems to have a favourable effect on the course of RA and may postpone the risk of RA onset during pregnancy.

Adult↗
PubMed1998

A genetic association study of the IGF-1 gene and radiological osteoarthritis in a population-based cohort study (the Rotterdam Study).

OBJECTIVE: A genetic association study was performed to investigate whether radiographical osteoarthritis (ROA) was associated with specific genotypes of the insulin-like growth factor I (IGF-1) gene. METHODS: Subjects aged 55-65 years were selected from a population-based study of which ROA at the knee, hip, spine, and hand was assessed. Genotypes were determined of a polymorphism in the promoter region of the IGF-1 gene. RESULTS: The IGF-1 locus was significantly associated with the presence of ROA (over-all adjusted OR for heterozygous subjects = 1.9, 95% CI 1.2, 3.1 and for homozygous subjects 3.6, 95% CI 0.8, 16.2). CONCLUSION: These results suggest that variation at the IGF-1 locus is associated with ROA development and may play a part in ROA pathogenesis. To confirm these findings replication in another population-based sample is needed.

Aged↗
PubMed1998

New insights in the pathogenesis of rheumatoid arthritis.

Recent advances in molecular technology as well as clinical research findings have enabled the identification of distinct cell subsets, cell surface markers, and cell products that contribute to the immune mediated inflammation observed in rheumatoid arthritis (RA). However, the lack of definitive insight into the disease etiology has resulted in various hypotheses about the roles of these cells or molecules in the pathophysiology of RA. This review summarizes arguments for and against the central role played by T cells in the initiation and perpetuation of RA. Although the available data do not exclude a role of any particular inflammatory mechanism, understanding of immunoregulatory functions of various T cell subsets may lead to more targeted and effective interventions.

Arthritis, Rheumatoid↗
PubMed1998

Combination therapy in recent onset rheumatoid arthritis: a randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine.

OBJECTIVE: To investigate whether there is interaction between chloroquine and cyclosporine (CyA) at the level of efficacy and toxicity in patients with recent onset rheumatoid arthritis (RA). METHODS: Eighty-eight patients with recent onset RA, who had shown a suboptimal clinical response on low dose chloroquine monotherapy, were randomly assigned to additional treatment with placebo, CyA 1.25 mg/kg/day, or CyA 2.50 mg/kg/day (fixed doses) for another 24 weeks. The tender joint count was the primary outcome assessment of efficacy and the serum creatinine of toxicity. The 1995 preliminary ACR response criteria for improvement were applied to evaluate individual clinical responses. RESULTS: Two patients in the placebo group (n = 29), 7 patients in the CyA 1.25 mg group (n = 29), and 8 patients in the CyA 2.50 mg group (n = 30) (p = 0.06) discontinued study medication prematurely for inefficacy or adverse events. The intention-to-treat analysis revealed that the tender joint count decreased 2.2 +/- 6.1 (mean +/- SD) joints in the placebo group, 2.2 +/- 6.6 joints in the CyA 1.25 mg group, and 5.0 +/- 5.8 joints in the CyA 2.50 mg group (p = 0.04). The 1995 preliminary ACR response criteria for clinical improvement were met by 8 (28%) patients in the placebo group, 10 (34%) patients in the CyA 1.25 mg group, and 15 (50%) patients in the CyA 2.50 mg group (p = 0.07). The serum creatinine increased 2 +/- 7 micromol/l in the placebo group, decreased 1 +/- 8 micromol/l in the CyA 1.25 mg group, and increased 10 +/- 15 micromol/l in the CyA 2.50 mg group (p < 0.001). CONCLUSION: The addition of low dose CyA is moderately effective in patients with early RA already treated with low dose chloroquine, but results in statistically significant renal function loss.

Adolescent↗
PubMed1998

Functional analysis of a human tumor necrosis factor alpha (TNF-alpha) promoter polymorphism related to joint damage in rheumatoid arthritis.

BACKGROUND: Functional heterogeneity in the tumor necrosis factor alpha (TNF-alpha) gene may be responsible for the TNF-alpha response in infectious and autoimmune diseases. Recently, the TNF-238 promoter polymorphism was observed as being associated with a more destructive disease in rheumatoid arthritis (RA). To determine the relation between TNF-238 and disease progression, the extent of joint destruction in a cohort of 101 RA patients followed for 12 years was analyzed. Furthermore, we have attempted to link this polymorphism to TNF-alpha gene transcription in monocytes and lymphocytes in vitro. PATIENTS, MATERIALS, AND METHODS: The extent of joint destruction determined on X-rays of hands and feet assessed after 0, 3, 6, and 12 years was compared with TNF-238 genotypes. Functional consequences of TNF-alpha gene polymorphisms using reporter gene constructs were analyzed in cells of the monocyte and lymphocyte lineage by means of transient transfection systems. RESULTS: The rate of joint damage in -238GA patients was lower than that in the -238GG patients, independent of HLA-DR4. Damage after 12 years was 76 +/- 30 for the -238GA versus 126 +/- 13 for the -238GG patients as determined by the van der Heijde's modification of Sharp's method. Furthermore, TNF-238A was found to be in linkage disequilibrium with an additional polymorphism at position -376. Functional assays revealed no significant differences in the level of inducible reporter gene expression between the TNF-238/-376 promoter constructs in the cell types tested. CONCLUSION: In a prospective study, we show that the TNF-238GG genotype contributes to progression of joint destruction in RA, independent of the presence of HLA-DR4. However, in vitro transfection assays indicate that TNF-238A by itself or in combination with TNF-376A is not likely to be of direct functional relevance for transcriptional activation. Therefore, these polymorphisms may serve as markers for additional polymorphisms in the TNF/LT locus or neighboring genes that may influence disease severity.

Adult↗
PubMed1997

[High-dose chemotherapy followed by hematopoietic stem cell transplantation as therapy for systemic rheumatic autoimmune diseases].

Remissions of autoimmune diseases can be accomplished in animals by myeloablative chemotherapy followed by allogeneic or autologous bone marrow transplantation. Remissions of autoimmune diseases have been reported in patients with concomitant malignancies for which they were treated with myeloablative chemotherapy followed by stem cell transplantation. Survival of patients with systemic rheumatic autoimmune disease is reduced. Since transplantation related mortality after autologous stem cell transplantation is less than 5%, this treatment becomes a possibility for patients with severe systemic rheumatic autoimmune disease, such as systemic sclerosis.

Adult↗
PubMed1997

Defective TCR-mediated signaling in synovial T cells in rheumatoid arthritis.

In rheumatoid arthritis (RA), the functional status of T cells is incompletely understood. Synovial T cells display phenotypic evidence of former activation, but there is poor production of T cell-derived cytokines in the synovium. In addition, synovial T cell proliferation upon mitogenic and antigenic stimulation was decreased compared with that in peripheral blood T cells. Moreover, previous reports revealed that early Ca2+ rises induced by TCR/CD3 stimulation were decreased in RA T cells compared with those in healthy controls. To investigate the molecular mechanisms of RA synovial T cell hyporesponsiveness, we analyzed the TCR/CD3-mediated protein tyrosine phosphorylation in RA peripheral blood and synovial fluid (SF) T cells. SF T cells exhibited a decreased overall tyrosine phosphorylation pattern upon stimulation. Most notably, the induction of phosphorylation of p38 was virtually absent. Moreover, we found that tyrosine phosphorylation of the TCR zeta-chain, one of the most proximal events in TCR signaling, is clearly diminished in RA SF T cells. The decrease in tyrosine phosphorylation was accompanied by a decrease in detectable levels of zeta-protein within synovial T cells. These results suggest that a defective TCR signaling underlies the hyporesponsiveness of synovial T cells in RA.

Arthritis, Rheumatoid↗
PubMed1997

[A new approach to rheumatoid arthritis].

Slow-acting antirheumatic drugs (SAARDs) are usually prescribed in rheumatoid arthritis only when non-steroid anti-inflammatory drugs can no longer suppress the inflammation or when articular damage is radiologically apparent. It was established recently that articular damage occurs in an early phase of RA. This damage is linked to subsequent disability; to prevent it is the purpose of SAARDs. In view of the short-term reduction of arthritis activity and improvement of function as well as the meanwhile established fact that the side effects of SAARDs are not different from those of other antirheumatic agents, SAARDs should be prescribed in an early phase of RA.

Antirheumatic Agents↗
PubMed1997

[Spondylodiscitis caused by Streptococcus agalactiae].

Two previously healthy adults, a man aged 69 and a woman aged 51 years, presented with spondylitis caused by Streptococcus agalactiae. One patient had fever and acute pain in the neck, the other progressive pain in the lower back. From cultures of blood and bone respectively. S. agalactiae was isolated. Both patients recovered after treatment with benzylpenicillin. S. agalactiae (group B streptococcus) is a wellknown cause of invasive infections in neonates and pregnant adults. Infections in nonpregnant adults are increasingly reported. Chronic conditions such as diabetes mellitus are strongly associated with disease caused by S. agalactiae.

Aged↗
PubMed1997

Evidence for the role of an altered redox state in hyporesponsiveness of synovial T cells in rheumatoid arthritis.

In rheumatoid arthritis (RA), T cells isolated from the synovial fluid (SF) show impaired responses to mitogenic stimulation compared with T cells from the peripheral blood (PB). Here it is reported that hyporesponsiveness of SF T cells correlated with a significant decrease in the levels of the intracellular redox-regulating agent glutathione (GSH). GSH was decreased in both CD4+ (p = 0.0022) and CD8+ (p = 0.0010) SF T cell subsets compared with PB CD4+ and CD8+ T cells in RA patients. Levels of thioredoxin (TRX), another key redox mediator, previously found to be secreted under conditions of oxidative stress, were found to be significantly increased in SF compared with plasma samples of RA patients (p = 0.005). Increased levels of TRX in the SF of inflamed joints was found to be associated with RA when compared with other arthritides (p = 0.007). Restoration of GSH levels in SF T cells with N-acetyl-L-cysteine (NAC), enhanced mitogenic induced proliferative responses and IL-2 production. Collectively, these data impute an important role to an altered redox state in the hyporesponsiveness of joint T cells in patients with RA.

Adult↗
PubMed1997

Increased expression of IL-15 in the synovium of patients with rheumatoid arthritis compared with patients with Yersinia-induced arthritis and osteoarthritis.

Recently, a new player in the cytokine network has been described that is produced by monocytes and can be detected in the rheumatoid synovium: interleukin-15 (IL-15). Since this cytokine may play a role in the accumulation and activation of T-cells, B-cells, and natural killer (NK) cells characteristic of synovial tissue (ST) from patients with rheumatoid arthritis (RA), the expression of IL-15 was studied in ST from RA patients in comparison with ST from patients with reactive arthritis (ReA) and osteoarthritis (OA) and the phenotype of IL-15-positive cells was determined. IL-15 expression was investigated by immunohistochemical analysis of ST from ten patients with RA, ten patients with Yersinia enterocolitica-induced ReA, and nine patients with OA. The immunohistological findings were quantified and the results obtained in the different patient groups were compared. To determine the phenotype of IL-15-expressing cells, double-labelling immunofluorescence was performed. The expression of IL-15 was significantly higher in ST from patients with RA than in ST from patients with ReA or OA. In double-label experiments, co-expression was observed with markers for macrophages, T-cells, and NK cells. The composition of the cellular infiltrate in the synovium of patients with RA might be partly explained by the specific increase in expression of IL-15 in rheumatoid ST. It can be speculated that IL-15 production by inflammatory cells other than macrophages may occur in the rheumatoid synovium.

Adult↗
PubMed1997

Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity.

OBJECTIVE: To define variations in the cellular infiltrate and in the expression of monokines in synovial tissue (ST) from rheumatoid arthritis (RA) patients with different durations of disease and different levels of disease activity. METHODS: The immunohistologic features of synovial biopsy specimens from 31 patients with early RA (< 1 year) and 35 patients with longstanding RA (> 5 years) were compared. The possible associations between these features and local disease activity, as measured by the score for pain in the biopsied knee joint were also evaluated. RESULTS: The immunohistologic features were not dependent on disease duration. We found a positive correlation between the scores for knee pain and the semiquantitative scores for the number of macrophages, as well as the expression of interleukin-6 and tumor necrosis factor alpha, whereas the correlation with the scores for CD4+ T cells was negative. Multivariate analysis showed that these correlations were highly statistically significant (P < 0.003). CONCLUSION: The results do not support the view that inflammatory mechanisms in the synovial tissues of RA patients differ between early and late stages of the disease. The findings presented here are consistent with the concept that early RA is the result of a synovitis process of longer duration and that macrophage-derived cytokines play an important role in maintaining the clinical signs of inflammation.

Adult↗
PubMed1997

Investigation of the association of the CRTM and CRTL1 genes with radiographically evident osteoarthritis in subjects from the Rotterdam study.

OBJECTIVE: To investigate whether radiographically evident osteoarthritis (ROA) in 55-65-year-old men and women is associated with specific alleles or genotypes of the cartilage matrix protein (CRTM) and cartilage link protein (CRTL1) genes. METHODS: Cases were selected from a population-based study on the presence of ROA of the knee or hip. Further radiographic analysis included scoring for spine and hand ROA. Controls, selected from the same population, were free of ROA in all joints. RESULTS: The CRTM locus was significantly associated with hip ROA in men (odds ratio 0.50, 95% confidence interval 0.26-0.95). A significant association between ROA and the CRTL1 gene was not observed. CONCLUSION: These results suggest that the CRTM locus may play a role in the sex- and joint site-specific pattern of ROA development.

Aged↗
PubMed1997

Treatment with a chimeric CD4 monoclonal antibody is associated with a relative loss of CD4+/CD45RA+ cells in patients with rheumatoid arthritis.

This study investigates immunogenicity and in vivo effects on T-cells of long-term CD4 monoclonal antibody treatment of patients with rheumatoid arthritis. Patients were treated with several dosage regimens of a chimeric CD4 monoclonal antibody entitled cM-T412 over the course of 1 year. The circulating CD4+ T-cell count sharply decreased after the first cM-T412 injection and slowly recovered after the last injection. Within the CD4+ subset there was a selective depletion of CD45RA+ T cells, HLA-DR+, and CD25+ cells, providing evidence that activated/memory CD4+ cells resist the effect of CD4 monoclonal antibodies. Studies on cytokine production by peripheral blood mononuclear cells cultures in vitro revealed no differential effect on the production of interleukin-4 compared to interferon-gamma, indicating that a shift from a Th1 to a Th2 lymphokine production profile was not achieved. Human anti-monoclonal antibodies (HAMA) were induced in a minority of the patients predominantly after the first treatment course. All the sera containing HAMA specifically inhibited the binding of cM-T412 to T-cells. However, HAMA formation does not interfere with the biological effect of repeated cM-T412 administration since the degree of CD4 depletion following repeated administration of cM-T412 to patients with and without blocking antibodies was similar. We conclude that the currently available data are of critical importance in the interpretation of the obtained clinical experience and for further development of this therapeutic strategy.

Adult↗