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Biomedical subjects

F C Breedveld

Publications and source records attributed to F C Breedveld.

At least 451 records · Page 25Linked to original sources
PubMedDate not supplied

An extended HLA-DQ-DR haplotype rather than DRB1 alone contributes to RA predisposition.

In the present study, we tested our hypothesis on the role of a DQ-DR haplotype in rheumatoid arthritis (RA) predisposition. Using two groups of patients and controls, one from The Netherlands and one from Switzerland, we found that DQA1*0301-homozygous and DQA1*0301//DQA1*0101/04-heterozygous individuals are highly predisposed to RA in both populations, while DQA1*0101/04-homozygous are not. The DQA1*0301-DRB1*0403/06/07 and DQA1*0301-DRB1*0901 haplotypes are not associated with RA by themselves but strongly increase the risk of developing disease in DQA1*0301- and DQA1*0101/04-heterozygous. DRB1 alleles carrying the motif DERAA in their third hypervariable region, i.e., *0103, *0402, *1102, *1103, *1301, and *1302, provide a long-lasting protection against RA in DQA1*0101/04- but not in DQA1*0301-positive individuals. These data show that considering both DQ and DR gives a better distinction between patients and controls than the shared epitope hypothesis.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Characterization of the hyporesponsiveness of synovial T-Cells in rheumatoid arthritis: role of chronic oxidative stress.

It is commonly thought that autoreactive T-cells fulfill a central role in the chronic inflammatory response that occurs in the joints of patients with rheumatoid arthritis (RA). However, the accumulated T-cells in the joints of patients with RA are functionally suppressed compared with peripheral blood T-cells. The mechanism that underlies this synovial T-cell hyporesponsiveness and the possible role of this phenomenon in the pathogenesis of RA is the subject of this article.

Journal Article↗
PubMedDate not supplied

The accuracy of diagnosing neuropsychiatric systemic lupus erythematosus in a series of 49 hospitalized patients.

OBJECTIVE: Neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) originate from immune-mediated disease (primary neuropsychiatric SLE) or from other pathogenetic mechanisms indirectly related to SLE (secondary neuropsychiatric SLE). The objective of this study is to describe the clinical practice of diagnosing NP-SLE and to assess how often the diagnosis of primary NP-SLE is changed to secondary NP-SLE and vice versa during the follow-up period in a large series of hospitalized SLE patients. MATERIALS AND METHODS: Data was collected by means of retrospective evaluation of the charts of 191 SLE patients admitted during the period 1986 to 1995. RESULTS: Of 191 admitted SLE patients, 49 had developed neuropsychiatric signs and symptoms. At admission 30 patients were classified as having primary NP-SLE and 19 patients secondary NP-SLE. During follow-up the diagnosis was changed to primary NP-SLE in 2 patients initially diagnosed as suffering from secondary NP-SLE, and in two patients from primary to secondary NP-SLE. Seizures, cognitive deterioration, psychosis and organic brain syndrome were the most frequent manifestations in primary NP-SLE, whereas in secondary NP-SLE headache, seizures, paresis and organic brain syndrome prevailed. 47% of the primary NP-SLE patients were re-admitted to hospital because of recurrent neuropsychiatric manifestations within 4.5 years, while 10% died due to primary NP-SLE. The prognosis of secondary NP-SLE was dependent on the diagnosis. CONCLUSION: In the large majority of patients the initial diagnosis of primary or secondary NP-SLE made upon their admittance to hospital is confirmed during the long-term follow-up.

Adolescent↗
PubMedDate not supplied

The effect of promoter strength in adenoviral vectors in hyperplastic synovium.

OBJECTIVES: To compare the activity of the CytoMegaloVirus promoter (CMV) and the Major Late promoter (MLP) in synoviocytes in vitro and in vivo. To determine the phenotype of infected cells and the induction of inflammation. To investigate the effects of the cytomegalovirus (CMV) or major late (MLP) promoter on adenovirus-mediated reporter gene transduction of synoviocytes in vitro and in vivo. METHODS: After infection with adenoviral vectors harboring CMV- and MLP-driven luciferase and lacZ genes, gene expression was examined in cultured synoviocytes and in the synovium of rhesus monkeys with collagen-induced arthritis. Immunohistochemical staining for the macrophage-marker CD68 and lacZ expression was performed. Inflammation was scored in the synovial membrane of injected and non-injected joints. RESULTS: CMV-driven reporter gene expression was found to be 6 to 10 times higher than MLP-driven gene expression in both cultured synoviocytes and monkey synovium. Both CD68 positive and CD68 negative cells were lacZ positive. Inflammation in joints injected with CMV-driven adenoviral vectors was not higher than that in MLP-driven adenoviral vectors- or non-injected joints. CONCLUSION: These experiments show that the CMV promoter induces higher gene expression in synoviocytes than the MLP promoter. Both fibroblast-like and macrophage-like synoviocytes can be infected with adenoviral vectors. No deleterious effects of the CMV-promoter driven adenoviral vectors were observed.

Adenoviridae↗
PubMedDate not supplied

No therapeutic effect of plasmin antagonist tranexamic acid in rheumatoid arthritis. A double-blind placebo-controlled pilot study.

OBJECTIVE: In the present study, the effects of plasmin antagonist tranexamic acid (TEA) on urinary pyridinoline excretion rates were investigated in rheumatoid arthritis (RA) patients. METHODS: The study was set up as a double-blind placebo-controlled pilot study. Ten patients received tranexamic acid and 9 received placebo for 12 weeks. Urinary excretion rates of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) were used as molecular markers of articular cartilage and bone degradation. In addition, clinical parameters of disease activity were assessed and CRP levels were measured. RESULTS: Treatment with TEA did not reduce pyridinoline excretion, nor was any effect observed on clinical parameters of disease activity or on CRP levels. CONCLUSION: The results of the present pilot study show no beneficial effect of TEA as adjuvant therapy in RA patients with respect to joint destruction or disease activity.

Amino Acids↗
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IgG and IgA autoantibodies to C1q in systemic and renal diseases.

Antibodies to the collagen-like region of C1q have been described in patients with SLE and rheumatoid vasculitis. In this study the prevalence of both IgG and IgA C1qAb was assessed in serum samples of 385 patients with different systemic and renal diseases. The results demonstrate that the prevalence of IgG and IgA C1qAb is not restricted to the diseases in which they were originally described. C1qAb can also be demonstrated in patients with MCTD, Felty's syndrome, ankylosing spondylitis, polyarteritis nodosa, mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, glomerulosclerosis, and patients with anti-glomerular basement membrane nephritis. The widespread occurrence of C1qAb of both immunoglobulin classes in systemic and renal diseases may provide insight into the mechanisms that lead to C1qAb formation.

Arthritis, Rheumatoid↗
PubMedDate not supplied

The Leiden Early Arthritis Clinic.

In 1993 a special Early Arthritis Clinic (EAC) was established at the Department of Rheumatology of the Leiden University Medical Center in order to detect and treat inflammatory disorders early in the disease state, especially early rheumatoid arthritis. Patients with confirmed arthritis of recent onset (less than 2 years) were included by rheumatologists and trained research nurses. Parameters of first and follow-up visits (3, 6 and 9 months and yearly) that were entered in the EAC-database include the medical history, physical-diagnostic examination, laboratory tests, questionnaires, radiographic joint scores and diagnosis. This database enables us to conduct research on arthritis, with an emphasis on rheumatoid arthritis, in many ways. Physicians and basic scientists have studied cellular immunology and genetic, environmental and clinical risk factors in order to determine the pathophysiologic mechanisms of inflammatory arthritis. The present article is a review on reports published from the EAC. Over the past ten years, these reports have been highly relevant for both daily clinical practice and research. Present and planned future studies, as described in this article, reconfirm the importance of an EAC framework to ensure that research continues on this disease in the Leiden EAC area.

Ambulatory Care Facilities↗
PubMedDate not supplied

Undifferentiated arthritis--disease course assessed in several inception cohorts.

The prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Because early aggressive treatment might offer an effective means to slow disease progression in RA, it is important to identify UA patients who will develop RA and treat them as early as possible. At the same time, inappropriate treatment of patients with a more benign disease course should be avoided. Here, an overview is given of the characteristics and numbers of patients with UA who evolve into RA. UA is defined as any arthritis that has the potential for a persistent course, without fulfilling the classification criteria for specific rheumatic disorders. To compare endpoints in the different databases, the 1987 ACR criteria for RA were used. In the nine databases employing a similar definition for undifferentiated arthritis, the proportion of patients with UA that evolved into RA within 1 year varied from 6% to 55%. These differences arise in large part from differences in the inclusion criteria and in the definitions used for UA and RA. The data from the various cohorts support a hypothesis that a considerable proportion of UA patients are actually patients with RA in a very early stage. Controlled intervention studies with early antirheumatic treatment in these patients are mandatory in order to provide further insight into the natural course of UA and to define a treatment strategy that will successfully slow or prevent disease progression.

Antirheumatic Agents↗
PubMedDate not supplied

Aiming at low disease activity in rheumatoid arthritis with initial combination therapy or initial monotherapy strategies: the BeSt study.

AIM: To evaluate the efficacy and safety of four different treatment strategies for patients with early rheumatoid arthritis (RA). METHODS: In the BeSt study, 508 patients with newly diagnosed (< 2 years) active RA were randomised to be treated according to four treatment strategies: 1. sequential monotherapy, 2. step up to combination therapy (both starting with methotrexate), 3. initial combination therapy with methotrexate, sulphasalazine, and a tapered high dose of prednisone, and 4. initial combination therapy with methotrexate and infliximab. Three-monthly therapy adjustments were dictated by calculation of the Disease Activity Score (DAS), with the goal to achieve and maintain a DAS <or= 2.4. Functional ability was measured every 3 months with the Health Assessment Questionnaire. Radiographs of hands and feet were assessed yearly, blinded for patient identity and treatment, and in random order, to measure joint damage progression (Sharp/van der Heijde score). RESULTS: After 2 years of treatment, 80% of all patients achieved the goal of DAS <or= 2.4, and 42% reached clinical remission (DAS < 1.6). Initial combination therapy, either with prednisone (group 3) or with infliximab (group 4), resulted in earlier improvement in functional ability, more continuous clinical remission (DAS < 1.6), and less joint damage progression than initial monotherapy (groups 1 and 2). Patients in groups 1 and 2 needed more therapy adjustments, including introduction of combination therapy with prednisone or infliximab, to achieve a DAS <or= 2.4, whereas many patients in groups 3 and 4 were able to taper their medication to sulphasalazine or methotrexate, respectively, monotherapy. The adverse events profile was comparable in all groups. The presence or absence of rheumatoid factor, HLA DR4, or anti-CCP was not associated with radiologic damage progression. CONCLUSION: In patients with early, active RA, remarkable clinical improvement and suppression of joint damage progression can be achieved with frequent, objectively steered treatment adjustments. The best chance for an early clinical and radiologic response lies with initial combination therapy with either methotrexate, sulphasalazine and prednisone or with methotrexate and infliximab, which can be tapered to DMARD monotherapy once low disease activity is achieved.

Adult↗
PubMedDate not supplied

Characterization of anti-endothelial antibodies in patients with rheumatoid arthritis complicated by vasculitis.

Anti-endothelial antibodies (AEA) have been described in patients with rheumatoid arthritis (RA) complicated by vasculitis. In this study we made use of an ELISA and immunoblot technique (IBT) to further characterize AEA of the IgG class in serum of patients with rheumatoid vasculitis (RV) and to investigate the relationship between the presence of IgG-AEA and vasculitis. IgG-AEA as measured by ELISA or IBT could be detected in the serum from 20 of the 23 (87%) RV patients, in 2 out of 13 (15%) patients with RA and in one of 15 healthy donors. The IBT revealed reactivity of IgG-AEA against a total of 12 bands of endothelial antigens ranging in size from 16 to 68 kD. IgG-AEA as measured by ELISA and IBT in serum samples of patients followed longitudinally were present more frequently and in higher titres in patients with active RV as compared to patients with vasculitis in remission. A significant correlation was found between the presence of clinical signs of vasculitis and serum IgG-AEA reactivity against an endothelial membrane antigen of 44 kD. These data show that the pattern of IgG-AEA reactivity in the serum of RV patients is heterogeneous and suggest that IgG-AEA against one particular antigen is involved in the pathogenesis of RV.

Antibodies↗
PubMedDate not supplied

Subcutaneous fat biopsy in the diagnosis of amyloidosis secondary to chronic arthritis.

Subcutaneous fat biopsy was investigated for its sensitivity in giving a diagnosis in 44 consecutive patients with rheumatoid arthritis or ankylosing spondylitis suspected of systemic amyloidosis. In 26 of these patients amyloidosis could be demonstrated by fat or rectal biopsy or biopsies from organs suspected of amyloid deposition. Fourteen of the 26 (54%) fat biopsy specimens of the patients with amyloidosis were positive after staining with Congo red and 22 (85%) of the rectal biopsy specimens were positive. All 12 kidney biopsy specimens and 4 biopsy specimens from other organs of these 26 patients were positive for amyloidosis. In 2 patients with a negative rectal biopsy specimen, fat biopsy would have obviated the need for a more invasive biopsy. All patients experienced fat biopsy as less demanding compared to other biopsy procedures. These results imply that in patients with chronic arthritis subcutaneous fat biopsy is a useful screening procedure. In this patient group fat biopsy is less sensitive for the diagnosis of amyloidosis compared to rectal biopsy.

Adipose Tissue↗
PubMedDate not supplied

Humoral immunity and composition of immune complexes in patients with rheumatoid arthritis, with special reference to IgE-containing immune complexes.

IgE-containing circulating immune complexes (IgE-CIC) were determined with a 2.5% PEG-precipitation assay in 98 patients with classical or definite rheumatoid arthritis (RA). Of the 45 IgE-CIC positive sera, only 4 had elevated total serum IgE. IgE-CIC positive patients had more active disease than patients without IgE-CIC, as determined by their more swollen joints and higher Ritchie indices (p less than 0.04 and 0.02, respectively). Apart from IgE, other immunoglobulin isotypes, rheumatoid factor (RF) of the IgG-, IgA- and IgM-classes, C3 and antinuclear antibodies could be demonstrated in the IgE-containing PEG-precipitates. IgE-RF could not be demonstrated in serum or in IgE-CIC. Anti-IgE of the IgM-class (IgMaIgE) were frequently found (28/45 patients) in the IgE-positive PEG-precipitates. All 14 patients positive for IgGaIgE in the IgE-CIC were also positive for IgMaIgE in the CIC. As in the serum, there was a good correlation in the CIC between the level of IgGaIgE and the level of IgMaIgE (r = 0.64). The correlation between the respective levels of IgGaIgE and IgMaIgE in serum and in CIC was high (r = 0.93 and 0.79, respectively). On the other hand, only 1 patient was positive for IgAaIgE in the IgE-CIC. We conclude that IgE and aIgE of the IgM- and IgG-classes are frequently present in the immune complex form in RA and that they are correlated with the clinical activity of arthritis.

Adult↗