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D Elewaut

Publications and source records attributed to D Elewaut.

48 records · Page 3Linked to original sources
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↗
PubMed1995

Gut inflammation in psoriatic arthritis: a prospective ileocolonoscopic study.

OBJECTIVE: Some forms of psoriatic arthritis (PsA) are classified as spondylarthropathy, and subclinical gut inflammation is found in spondylarthropathies. Our study was designed to determine if inflammatory gut lesions were also present in PsA, and if the prevalence of subclinical gut involvement was different in the subgroups of this disease. The relationship with HLA subtypes was also determined. METHODS: Ileocolonoscopy was performed on 64 patients with PsA (37 men, 27 women). RESULTS: Inflammatory gut lesions were found in 10 of the 64 patients (16%): in 3 of the 15 patients (20%) with oligoarthritis and in 7 of the 23 patients (30%) with axial involvement. None of the 26 patients with polyarthritis showed these lesions. The prevalence of HLA-B27, Bw62, and B17 was significantly raised in our total group of patients with PsA. HLA-B27 and Bw62 were significantly more prevalent in patients with gut inflammation, 60 and 50%, respectively. CONCLUSION: Gut inflammation is only present in PsA subgroups that belong to the spondylarthropathy concept. This suggests that the gut plays a role in the pathogenesis of locomotor inflammation in these subgroups. The prevalence of gut inflammation in psoriatic spondylarthropathy is significantly lower than in nonpsoriatic spondylarthropathies. Consequently, not only the gut but also the skin may be a portal of entry for causative antigens in PsA.

Adolescent↗
PubMed1995

The evolution of spondyloarthropathies in relation to gut histology. I. Clinical aspects.

OBJECTIVE: To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) (excluding inflammatory bowel disease, IBD): reactive arthritis, undifferentiated SpA, and ankylosing spondylitis (AS). METHODS: Ileocolonoscopy was performed on 217 patients with SpA (149 men, 68 women). They also underwent clinical, laboratory, and radiological examinations. Two to 9 years later, 123 patients (84 men, 39 women) who had been regularly monitored were reviewed and given the same examinations. For the remaining 94 patients clinical data were obtained by telephone. RESULTS: At the time of clinical review, 53 (43%) of the regularly monitored patients were in clinical remission. The remission rate was higher in patients with non-ankylosing spondylitis SpA (non-As-SpA) than in patients with AS (19%). Fourteen patients with non-AS-SpA had developed AS; 4 of them also had IBD. IBD was also found in 4 patients with AS and in 3 patients from the telephone group. The prevalence of HLA-B27 was significantly higher in all SpA subgroups, while HLA-BW62 was elevated in the undifferentiated SpA. At review, HLA-B27 was significantly more prevalent in patients with persistent locomotor inflammation compared to patients in clinical remission, while HLA-BW62 was predominant in the latter group. CONCLUSION: Patients with SpA, especially those with non-AS-SpA, have a good longterm prognosis. However, patients with non-AS-SpA may develop AS. Six percent of the patients with SpA in whom manifestations of IBD are absent will develop this disease. This confirms the hypothesis that some of these patients with SpA initially have a form of subclinical Crohn's disease, of which locomotor inflammation is the only clinical expression. HLA-B27 positivity predisposes to a more severe course of locomotor inflammation, while HLA-BW62 has a protective effect but is associated with gut inflammation.

Adolescent↗
PubMed1995

The evolution of spondyloarthropathies in relation to gut histology. II. Histological aspects.

OBJECTIVE: To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) in relation to the type of gut histology in ileocolonoscopic biopsy specimens. METHODS: Ileocolonoscopy was performed in 217 patients with SpA (149 men, 68 women). Three types of gut histology (normal gut histology and acute and chronic inflammatory gut lesions) were found. Clinical, laboratory, and radiological examinations were performed at start and 2 to 9 years later in 123 patients who were regularly monitored. For the remaining 94 patients clinical data were obtained by telephone. RESULTS: Of the 123 patients monitored regularly, 40 (32%) had normal gut histology, and 28 (23%) had acute and 55 (45%) chronic inflammatory gut lesions. Acute lesions were preferentially found in patients with non-ankylosing spondylitis SpA (non-AS-SpA). In the groups with normal gut histology and with chronic gut inflammation, patients with ankylosing spondylitis (AS) and non-AS-SpA were present in equal numbers. At review, clinical evolution was identical in the 3 histological subgroups. Eight patients developed idiopathic inflammatory bowel disease (IBD), one with initially acute gut inflammation, 7 with initially chronic gut inflammation. All had active AS at review. Fourteen patients with non-AS-SpA developed AS; 13 of them had initially presented inflammatory gut lesions. Three patients in the telephone group also developed IBD; all had active AS at review and initially presented chronic inflammatory gut lesions. Persistently high inflammatory serum variables, HLA-B27 negativity in the presence of sacroiliitis or AS, and inflammatory gut lesions at the first ileocolonoscopy indicate patients with SpA are at risk for developing IBD. CONCLUSION: Gut inflammation, mainly subclinical, could be demonstrated in 68% of patients with SpA. Acute gut inflammation was predominant in patients with reactive arthritis (ReA). The evolution to clinical remission was not influenced by the presence or the type of gut inflammation at start. Patients with non-AS-SpA with inflammatory gut lesions have greater risk of developing AS. One patient with Yersinia induced ReA developed AS and IBD. In total, 11 patients (66%) developed IBD, all initially presenting inflammatory gut lesions. Ten had chronic gut lesions, suggesting this type of gut inflammation is related to the inflammation of Crohn's disease. This type of gut inflammation, the persistence of high inflammatory serum variables, and the absence of HLA-B27 in patients with AS are risk factors for developing IBD.

Adolescent↗
PubMed1995

The evolution of spondyloarthropathies in relation to gut histology. III. Relation between gut and joint.

OBJECTIVE: To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) in relation to the evolution of gut histology in consecutive ileocolonoscopic biopsy specimens. METHODS: Ileocolonoscopy was performed in 49 patients with SpA (34 men, 15 women). They also underwent clinical, laboratory, and radiological examinations. Two to 9 years later, a 2nd and sometimes a 3rd or 4th ileocolonoscopy was performed, and the other examinations were repeated. RESULTS: At first ileocolonoscopy, 34 patients (69%) showed inflammatory gut lesions. At the 2nd ileocolonoscopy, 16 patients (32%) were in clinical remission; none were found to have inflammatory gut lesions. Of the 33 patients with persistent locomotor inflammation, 14 had persistent inflammatory gut lesions, predominantly the chronic type. Of these 14 patients, 6 had developed inflammatory bowel disease (IBD). None of the 15 patients with an initially normal gut histology had gut inflammation at 2nd examination. Of the 9 with initially acute lesions, 3 developed chronic lesions (1 Crohn's disease). Initial chronic lesions in 25 patients persisted in 9, of whom 5 had developed IBD. Seven of the 19 patients with non-SpA ankylosing spondylitis (non-AS-SpA) developed ankylosing spondylitis (AS); all had initially presented inflammatory gut lesions, which persisted at 2nd examination. In the 11 patients with more than 2 consecutive ileocolonoscopies, clinical remission was always associated with normal gut histology, and flares of the joint disease were related temporally to the reappearance of gut inflammation. CONCLUSION: This study demonstrates the close relationship between gut and locomotor inflammation in SpA. Clinical remission was always associated with normal gut histology, whereas active locomotor inflammation was usually associated with the presence of gut inflammation. Absence of gut inflammation in the SpA is a good prognostic indicator, since gut inflammation or IBD never develops in these patients. Evolution of non-AS-SpA to full blown AS or of uncomplicated SpA to a form of IBD was always associated with gut inflammation at disease onset.

Adolescent↗
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↗
PubMedDate not supplied

Immune-mediated pathology following hepatitis B vaccination. Two cases of polyarteritis nodosa and one case of pityriasis rosea-like drug eruption.

The association of hepatitis B virus infection and vasculitis or other immune-mediated manifestations is well documented. Reports on such manifestations in relation to hepatitis B vaccination are scarce, however. We report 2 patients who developed polyarteritis nodosa following vaccination against hepatitis B. In one patient this resulted in an ischemic and necrotic digital ulcus, necessitating surgical amputation. The other patient presented with typical cutaneous polyarteritis nodosa which responded well to corticosteroid treatment. A third patient developed a severe pityrias rosea-like eruption. He was treated with topical steroids with healing of the lesions, leaving only post-inflammatory hyperpigmentation. The literature on these associations is reviewed.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Broadening of the T cell receptor spectrum among rheumatoid arthritis synovial cell-lines in relation to disease duration.

OBJECTIVE: The aim of the study was to evaluate the T cell receptor (TCR) family usage in T cell-lines from subcutaneous nodules and synovium from patients with rheumatoid arthritis (RA), with specific reference to the duration of symptoms. In vitro adherence characteristics of nodular T cells was studied as well. METHODS: Monoclonal antibodies were used to determine the distribution of TCR families in T cell-lines from synovium of patients with early and long-standing RA, from rheumatoid nodules and control tissues. An in vitro binding assay with T cell-lines from 2 rheumatoid nodules was performed. RESULTS: In early RA synovium, a restricted TCR family usage was observed in 5 out of 8 patients, contrary to long-standing disease, peripheral blood, ileum and colon. In RA nodules, a similar degree of restriction was noted. Moreover, the same TCR family was overexpressed by T cell-lines from different nodules derived from the same patient. T cell-lines from rheumatoid nodules demonstrated a preferential in vitro adherence to rheumatoid synovium and rheumatoid nodules, while no binding was observed on skin or tonsil. CONCLUSION: The TCR spectrum among RA synovial cell-lines broadens in relation to the disease duration. The overexpression of the same TCR family in different rheumatoid nodules from the same patients, and the in vitro adherence of T cell-lines from rheumatoid nodules may be indicative for recirculation between the different disease manifestations in RA.

Adult↗
PubMedDate not supplied

Gut mucosal T cell lines from ankylosing spondylitis patients are enriched with alphaEbeta7 integrin.

OBJECTIVE: An intriguing link between gut and synovial inflammation exists in patients with spondyloarthropathy (SpA), illustrated by the high frequency of microscopically inflammatory gut lesions observed in these patients. We hypothesise that aberrant homing of mucosal T cells might play a role in the induction/perpetuation of arthritis in SpA. Here, we analyse the expression of the homing molecules alpha4beta7 and alphaEbeta7 on mucosal T cells from patients with ankylosing spondylitis (AS) and controls, in view of the critical role of these receptors in the homing of mucosal lymphocytes. METHODS: Colonic biopsy specimens were obtained from patients with AS (n = 23) and controls (n = 30). Biopsy specimens were immunostained, treated for extraction of intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) or cultured in the presence of IL-2. The expression of the beta7 integrins was investigated. RESULTS: In situ no differences were observed in alphaEbeta7 and alpha4beta7 integrin expression in isolated IEL and LPL, whether determined by flow cytometry or by immunohistochemical staining. In gut mucosal T cell lines, alphaEbeta7 expression was significantly higher in the mucosa of patients with AS compared with controls. Alpha4beta7 was highly expressed on T cells in both groups studied. Mucosal T cells either expressed only the alpha4beta7 integrin or co-expressed the alpha4beta7 and alphaEbeta7 integrins. Almost none of them expressed only the alphaEbeta7 integrin. CONCLUSION: In gut mucosal T cell lines from patients with AS an increased expression of alphaEbeta7 was observed.

Adolescent↗
PubMedDate not supplied

Altered expression of alpha E beta 7 integrin on intra-epithelial and lamina propria lymphocytes in patients with Crohn's disease.

OBJECTIVE: To compare the expression of adhesion molecules on intestinal intra-epithelial (IEL) and lamina propria T cells (LPL) from ileum and colon, in patients with Crohn's disease (CD) versus healthy controls, with special reference for the alpha E beta 7 integrin. METHODS: IEL and LPL were obtained from 18 CD patients and 20 controls by enzymatic extraction, and subsequently characterized by flow cytometry for CD3, CD4, CD8, CD25, LFA-1 alpha (CD11a), CD44, alpha 4 and alpha E beta 7 integrin. RESULTS: In LPL of controls, a decreased CD4/CD8 ratio was noted in ileum compared to colon. This regional difference was accompanied by a higher expression of alpha E beta 7 integrin in ileum versus colon. In LPL from left hemicolon of CD patients, a decreased CD4/CD8 ratio was noted versus controls. alpha E beta 7 expression on T cells of LPL did not discriminate CD from controls. However, an overexpression of this beta 7 integrin member was observed on CD25+ T cell subsets from lamina propria of left hemicolon, in CD versus controls. Moreover, in IEL, profound alterations in alpha E beta 7 integrin were observed in CD, compared to controls. A decreased expression of alpha E beta 7 was noted in IEL of ileum of CD patients. This was also apparent in non-inflamed mucosa. CONCLUSION: The observed changes of alpha E beta 7 integrin expression in CD patients versus controls are of pathogenic relevance, especially the decreased expression of alpha E beta 7 in IEL of non-inflamed CD mucosa. This may be one of the earliest events in the pathogenesis of this disease.

Adolescent↗