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Biomedical subjects

F De Keyser

Publications and source records attributed to F De Keyser.

At least 73 records · Page 4Linked to original sources
PubMed1999

Polyarteritis nodosa mimicking polymyalgia rheumatica.

We report a case of polyarteritis nodosa with a clinical presentation mimicking polymyalgia rheumatica, as well as pathological findings of non-giant-cell arteritis on temporal artery biopsy with symptoms of jaw claudication. Although certain clinical syndromes have been attributed to specific types of systemic vasculitis, considerable overlap occurs. Obtaining tissue biopsy in cases of vasculitis is mandatory for diagnosis and classification.

Aged↗
PubMed1999

Needle arthroscopy of the knee with synovial biopsy sampling: technical experience in 150 patients.

Needle arthroscopy is an office-based technique allowing direct visualisation of the knee cavity and selective sampling of the synovial membrane. We performed needle arthroscopy in 150 patients with synovitis of the knee (1) to evaluate the diagnostic potential in early arthritis, (2) to perform therapeutic lavage in persistent inflammatory synovitis and (3) to assess the balance between technical feasibility, safety and patient comfort on the one hand, and the relevance of the obtained macro- and microscopic information for diagnosis and research purposes on the other. After disinfection of the leg and local anaesthesia of the skin and joint, a 1.8-2.7 mm needle arthroscope was introduced into the knee. Synovial fluid was aspirated and lavage of the joint cavity was performed to allow macroscopic evaluation of hyperaemia and hypertrophy of the synovial membrane. Biopsies were taken at inflamed sites, followed by another lavage to remove blood and debris. Needle arthroscopy of the knee is a simple and easy to perform technique made particularly attractive by the local anaesthesia and the ambulatory setting. It allows good macroscopic evaluation of synovial inflammation and selective sampling of the synovial membrane. Biopsies are suitable for RNA and DNA extraction, bacterial or lymphocyte culture, and cell isolation. Because samples were sometimes too small for representative histology, we switched from a 1.8 mm to a 2.7 mm biopsy forceps with good results. In nearly all cases the arthroscopy was well tolerated. Moreover, some patients reported relief of symptoms and even improvement of mobility after lavage of the inflamed joint. No major complications were noted. It was concluded that needle arthroscopy of the knee is a simple, safe and well-tolerated technique, with promising perspectives as a diagnostic, scientific and possibly therapeutic tool in rheumatic diseases.

Adolescent↗
PubMed1998

Bowel inflammation and the spondyloarthropathies.

The concept of spondyloarthropathies gathers together a group of chronic diseases in which not only the locomotor system is involved but also other organs, especially the gastrointestinal tract. In humans, ileocolonoscopic studies demonstrated the presence of inflammatory gut lesions in all the diseases in the spondyloarthropathy group; their presence varied in the different diseases between 20% and 70%. The inflammation could be related to specific disease features in the spondyloarthropathies. Further research supports the hypothesis of subclinical inflammatory bowel disease in some patients with spondyloarthropathy, in which the locomotor inflammation was the only clinical manifestation. The link between gut inflammation and arthropathy has also been demonstrated in animal models, notably the human leukocyte antigen B27 transgenic rats. The temporal relationship between activity and severity of colonic involvement and flares of peripheral arthritis directs treatment of choice. For all forms of enterogenic arthropathies, nonsteroidal anti-inflammatory drugs remain the acute treatment form. Caution is in order, however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation.

Animals↗
PubMed1998

Review article: bone and joint diseases in inflammatory bowel disease.

The intestinal and articular systems are closely linked in inflammatory bowel disease. Clinical and immunological studies support an important aetio-pathogenetic link between intestinal and articular inflammation. There is increasing evidence for a negative link between bone mass density and intestinal inflammation. This paper will focus on the prevalence, aetio-pathogenesis and treatment of arthritis (peripheral, sacroiliitis and spondylitis) and osteoporosis in inflammatory bowel disease.

Animals↗
PubMed1998

Distinctive activated cellular subsets in colon from patients with Crohn's disease and ulcerative colitis.

BACKGROUND: Activated lymphocytes are considered to play a pathogenic role in Crohn's disease (CD) and ulcerative colitis (UC), although only a limited fraction of the gut-residing lymphocytes in these diseases may be pathogenetically involved, due to active recruitment from the peripheral circulation. Our aim was to characterize in situ preactivated lymphocytes in inflammatory bowel disease mucosa by expansion with interleukin-2. METHODS: Flow cytometry was performed on T cells expanded from the colon of patients with CD (7), UC (16), and controls (20), with special reference to T-cell activation markers and adhesion molecules. RESULTS: In CD a decrease in alpha4beta7 integrin expression was associated with an increase in alphaEbeta7. In UC a similar increase in alphaEbeta7 was observed. Moreover, L-selectin and CD30 were overexpressed on T helper cells in UC versus CD. CONCLUSION: These findings indicate different immunopathogenic pathways for CD and UC.

Biomarkers↗
PubMed1998

A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers.

OBJECTIVES: (1) To analyse the in situ expression of adhesion molecules in rheumatoid nodules. (2) To compare the endothelial expression of adhesion molecules in synovial tissue and subcutaneous nodules obtained from the same patients. (3) To compare the expression of adhesion molecules and activation markers on T cell lines from nodules and synovium. METHODS: (1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n = 7) and synovium (n = 7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of alpha E beta 7, alpha 4 beta 7, CD44, L selectin, LFA-1a, PECAM-1, and CD30. RESULTS: (1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium. CONCLUSION: These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.

Adult↗
PubMed1998

Enrichment of T cells carrying beta7 integrins in inflamed synovial tissue from patients with early spondyloarthropathy, compared to rheumatoid arthritis.

OBJECTIVE: To compare the expression of adhesion molecules on synovial T cells from patients with early spondyloarthropathy (SpA) and rheumatoid arthritis (RA), with special reference to the beta7 integrins alpha4beta7 and alphaEbeta7 in view of their intimate association with intestinal tissue. METHODS: Twenty-five synovial cell lines were generated by interleukin 2 (IL-2) expansion from synovial biopsies of patients with early SpA and RA, obtained from macroscopically inflamed synovial tissue by needle arthroscopy, and subsequently characterized by flow cytometry for CD3, CD4, CD8, L-selectin, CD11a, CD31, CD44, and alpha4beta7 and alphaEbeta7 integrin. RESULTS: In SpA, the beta7 integrin expression was increased, compared to RA. Furthermore, an inverse relation between alpha4beta7 and alphaEbeta7 was present in SpA (r = -0.75, p < 0.02), as on many mucosal T cells. In contrast, an opposite correlation was noted in RA (r = +0.84, p < 0.01), as similarly described on a subset of circulating T cells. CONCLUSION: Increased expression of beta7 integrins was noted on synovial T cell lines from SpA compared to RA, with discriminative correlations between alpha4beta7 and alphaEbeta7. This suggests a different origin of the synovial T cells in these diseases.

Adolescent↗
PubMed1997

Dominant T cell receptor rearrangements in interleukin 2 expanded lymphocytes from rheumatoid nodules suggest antigen driven T cell activation in situ.

OBJECTIVE: To study at a molecular level the clonality of interleukin 2 (IL-2) expanded T cell lines derived from rheumatoid nodules. Such cell lines were reported in earlier studies with flow cytometry and antiidiotypic monoclonal antibodies (MAb) to be obligoclonal. METHODS: T cell lines were derived from rheumatoid nodules in 2 patients with rheumatoid arthritis (RA) and expanded in medium containing IL-2. Clonality was assessed by flow cytometry and T cell receptor (TCR) idiotype specific Mab and by polymerase chain reaction with primers for V alpha and V beta gene families. Sequence analysis was performed in selected cell lines. RESULTS: In one patient, one cell line was identified with marked overexpression of V alpha 2 cells. Eleven V alpha 2 CDR3 sequences were derived from this cell line: 8 of these clones had an identical CDR3 sequence and one other clone showed a related sequence. Five cell lines derived from a second patient displayed a marked clonal bias to V beta 8 cells. One cell line with strong V beta 8 expression was chosen for further sequence analysis. Twelve V beta 8 sequences were obtained; 11 showed identical CDR3 sequences. CONCLUSION: Molecular analysis of TCR rearrangements in IL-2 expanded T cell lines from rheumatoid nodules strongly suggests that in situ T cell activation is related to classical antigen induced immune activation.

Aged↗
PubMed1996

Polyarteritis nodosa and the antiphospholipid syndrome.

We report a case of biopsy-proven polyarteritis nodosa (classic type in association with the antiphospholipid syndrome. Medium-sized arteriopathy was confirmed on visceral angiography. Elevated anticardiolipin antibodies were detected before initiating therapy with methylprednisolone and IV pulse cyclophosphamide. Rapid subsidence of symptoms correlated with a gradual normalisation of the erythrocyte sedimentation rate. After 6 months of therapy anticardiolipin antibodies were within normal limits. Only one similar case has been reported so far.

Angiography↗
PubMed1996

The gut associated addressins: lymphocyte homing in the gut.

The process of lymphocyte trafficking is mainly regulated by receptors that belong to a group of molecules referred to as adhesion molecules. These molecules can be divided, according to their molecular structure, into three broad families: the integrins; the selectins; and the immunoglobulin superfamily members. The alpha 4 beta 7 integrin is expressed on some lymphocytes with hallmarks of gut tropism. alpha 4 beta 7, among others, serves as a ligand for the mucosal vascular addressin MadCAM-1, which is selectively expressed on mucosal lymphoid organ high endothelial venules and on gut lamina propria venules. It is tempting to believe that related integrin receptors play a crucial role in the recirculation of activated lymphocytes between the gut mucosa and the synovial membrane.

Animals↗
PubMed1995

The role of T cells in rheumatoid arthritis.

The most striking arguments in favor of a T cell dependent nature of RA are the strong association of the disease with selected class II HLA haplotypes (the "shared epitope" hypothesis) and the fact that, in experimental animal models such as adjuvant arthritis, the disease can be transferred by isolated T cell lines. It is true that T cell activation at the site of inflammation is not excessive. However, there is now unequivocal evidence for focal synthesis of IL-2 and IFN-gamma in the RA synovial membrane and one may realise that a limited but specific T cell activation may be sufficient to induce or perpetuate the immune process. This same argument may explain the lack of clear TCR restriction at the sites of inflammation. Until now, no antigen has been demonstrated to initiate and/or perpetuate RA. Different antigens though have been incriminated in the pathogenesis of RA, including cartilage antigens (collagen, proteoglycans, chondrocyte antigens), heat shock proteins or exogenous (viral/bacterial) antigens. Unless one can pick up the right antigen and clone the relevant T cells, it will be very hard to directly prove a T cell-dependent nature of the disease.

Animals↗
PubMed1994

An optimized method for routine HLA-B27 screening using flow cytometry.

Flow cytometry and monoclonal antibodies are promising tools for HLA-antigen detection. Previous approaches have been hampered by the lack of a carefully standardized system for calibration and sample analysis. A new system for HLA-B27 screening was developed using a FACScan flow cytometer, software for automated calibration and analysis, calibration beads, and the anti-HLA-B27-FITC/anti-Leu4-PE (CD3) monoclonal antibodies. The median fluorescence channel result for the HLA-B27-FITC signal of CD3+ T lymphocytes is compared to a decision marker. Values lower than this threshold are read as HLA-B27 negative and those above are recommended for retesting with the classic microcytotoxicity assay on the presumption of HLA-B27 positivity. The anti-HLA-B27 antibody reacts with all six HLA-B27 subtypes and shows a weaker binding to HLA-B7. The screening test results were compared with those from the microcytotoxicity assay for HLA-typing in studies involving several European centers. The observed sensitivity was 100% (95% Cl:98.6-100) and the specificity was 97.4% (95% Cl: 96.4-98.3). Other performance studies verified the reproducibility and reliability of results obtained with the screening system.

Anticoagulants↗
PubMed1993

T cell receptor V beta usage in rheumatoid nodules: marked oligoclonality among IL-2 expanded lymphocytes.

Rheumatoid arthritis is an autoimmune disease which is characterized by chronic polyarthritis and joint destruction as well as by extra-articular manifestations, typically including the appearance of rheumatoid nodules. Although the pathogenesis of the disease is unknown, substantial evidence suggests that it is T cell-mediated. In contrast to experimental models, the disease-mediating T cells in the human situation have never been isolated or identified. We expanded T lymphocytes from human rheumatoid nodules by IL-2 stimulation and observed a marked oligoclonality among these expanded lymphocytes. This tendency towards oligoclonality was not seen in IL-2-expanded lymphocytes from peripheral blood. We hypothesize that this oligoclonal expansion reflects a clonally restricted in situ preactivation of lymphocytes and that precisely these preactivated cells are involved in the pathogenesis of the rheumatic process.

Aged↗
PubMed1992

Cross-reactivity of the B/B' subunit of the Sm ribonucleoprotein autoantigen with proline-rich polypeptides.

Using recombinant fusion proteins representing different regions of the human Sm B/B' polypeptide, the 4B4 monoclonal anti-Sm antibody was found to bind a C-terminus epitope that is proline-rich. 4B4 cross-reacted with the p24 gag protein of HIV-1 and with other polypeptides rich in proline residues, including collagen. BALB/c mice immunized with human collagen not only produced antibodies to the immunizing antigen but also antibodies to Sm. This immune mouse serum also recognized C-terminus B/B' fusion proteins. These data suggest that the Sm B/B' antigen contains a poly-Pro epitope that is shared by several autoantigens and retroviral proteins. These sites may be important in the induction of autoantibodies through molecular mimicry.

Animals↗