Search PubMed⌕ Search

Biomedical subjects

J W Tervaert

Publications and source records attributed to J W Tervaert.

At least 73 records · Page 4Linked to original sources
PubMed1994

Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis.

OBJECTIVE: To examine possible risk factors for relapse, including chronic nasal carriage of Staphylococcus aureus and serial antineutrophil cytoplasmic antibody (ANCA) determinations in patients with Wegener granulomatosis. DESIGN: Observational cohort study. SETTING: Outpatient clinic at a university-affiliated hospital. PATIENTS: Consecutive patients (n = 71) with biopsy-proven Wegener granulomatosis who were seen during follow-up at the outpatient clinic from January 1988 to July 1991. Fourteen patients were ineligible or dropped out; 57 patients were analyzed. MEASUREMENTS: Serial ANCA determinations and swab cultures of both anterior nares for S. aureus taken at each visit every 4 to 6 weeks. Occurrence of infections and relapses of Wegener granulomatosis were identified according to strict, predefined criteria. RESULTS: Thirty-six of the 57 patients (63%; 95% CI, 49% to 76%) were found to be chronic nasal carriers of S. aureus (> or = 75% of nasal cultures positive for S. aureus). Proportional-hazards regression analysis identified chronic nasal carriage of S. aureus (adjusted relative risk, 7.16; CI, 1.63 to 31.50), creatinine clearance above 60 mL.min-1 (adjusted relative risk, 2.94; CI, 1.27 to 6.67), and a history of previous relapses of Wegener granulomatosis (adjusted relative risk, 1.33; CI, 0.98 to 1.78) as independent risk factors for relapse. Twenty-two of 33 patients persistently or intermittently positive for ANCA had a relapse as opposed to only 1 of 21 persistently negative patients. Relapses of Wegener granulomatosis were not related to diagnosed infections. CONCLUSION: Chronic nasal carriage of S. aureus identifies a subgroup of patients with Wegener granulomatosis who are more prone to relapses of the disease, suggesting a role for S. aureus in its pathophysiology and a possible clue for treatment.

Adult↗
PubMed1994

Serum levels of soluble adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin in patients with Wegener's granulomatosis. Relationship to disease activity and relevance during followup.

OBJECTIVE: To assess the value of measuring serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAMP-1), and soluble E-selectin for monitoring disease activity in Wegener's granulomatosis (WG). METHODS: A sandwich enzyme-linked immunosorbent assay was used to measure levels of soluble adhesion molecules at the time of diagnosis in 22 consecutive patients with WG, in 12 WG patients studied serially prior to disease relapse, at the time of upper airways infection in 18 patients with inactive WG, and in 57 controls. Disease activity was assessed by disease activity score and C-reactive protein levels. RESULTS: At diagnosis of WG, sICAM-1 and sVCAM-1 levels were significantly elevated and correlated with disease activity. At the time of relapse, a significant increase in all 3 soluble adhesion molecules was found compared with levels at 6 months prior to relapse, but only sVCAM-1 levels were significantly elevated compared with those in controls. Levels of soluble adhesion molecules at the time of relapse did not differ from those measured during an upper airways infection without disease activity. CONCLUSION: Elevated serum levels of sICAM-1 and sVCAM-1 can be found in active WG and correlate with disease activity. However, their clinical relevance for followup is limited due to lack of sensitivity and specificity for WG disease activity.

Adolescent↗
PubMed1994

Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with inflammatory bowel disease (IBD). Relation to disease pattern and disease activity.

Anti-neutrophil cytoplasmic antibodies producing a perinuclear fluorescence pattern on ethanol-fixed granulocytes (p-ANCA) were found in 33 of 67 patients (49%) with ulcerative colitis (UC) but also in 14 of 35 patients (40%) with Crohn's disease (CD). In the latter condition p-ANCA were equally present in subgroups with colonic, ileocolonic, or ileal involvement only. Titers of p-ANCA were higher in patients with UC compared to CD patients, in particular when comparing patients with active disease. In contrast to findings in CD, patients with active UC had higher titers of p-ANCA than patients with inactive UC. Although p-ANCA were incidentally directed to lactoferrin, both in UC and CD, and to proteinase-3 and myeloperoxidase in UC only, the antigenic nature of p-ANCA could not be identified in most of the cases. We conclude that, within the spectrum of inflammatory bowel disease, the presence of p-ANCA is not specific for UC. When titers of p-ANCA are taken into account, the presence of high-titered p-ANCA, however, suggests active UC.

Adolescent↗
PubMed1994

Neutrophil activation in vitro and in vivo in Wegener's granulomatosis.

The mechanisms underlying glomerular capillary wall injury in Wegener's granulomatosis (WG) are not well understood. Anti-neutrophil cytoplasmic antibodies (ANCA), present in sera from patients with WG, are known to stimulate respiratory burst and degranulation of primed polymorphonuclear neutrophils (PMN) in vitro. Experimental studies have shown that oxygen radical production and lysosomal enzymes are important mediators of glomerular capillary wall injury. In the present study we investigated the presence of activated PMN and the extracellular localization of lysosomal enzymes in 28 consecutive renal biopsies from patients with WG. The presence of activated PMN within the renal biopsies was compared with the capacity of ANCA, isolated from simultaneously drawn serum samples, to activate primed PMN obtained from a normal donor. Both parameters were also related to renal function. Renal biopsies were obtained from newly diagnosed WG patients before therapy had started. Activation of PMN in the biopsies was assessed by measuring hydrogen peroxide production in situ. The number of activated PMN in the biopsy correlated with the extent of impairment of renal function. Proteinase 3, myeloperoxidase, and elastase, all targets of ANCA, were localized extracellularly in renal tissue and were also found within tubular epithelial cells. All ANCA positive samples were capable of activating primed PMN. The amount of activation correlated with the ANCA titer in those samples. No correlation, however, was found between the in vitro capacity of ANCA-positive IgG fractions to activate primed PMN and the number of activated PMN present in the renal biopsy. We conclude that activated PMN producing toxic oxygen metabolites and releasing lysosomal enzymes, are present in renal biopsies from patients with WG. The amount of activated PMN present within the kidney, and not the capacity of the corresponding ANCA to activate PMN, correlates with renal tissue damage as assessed by serum creatinine levels.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Anti-neutrophil cytoplasmic antibodies: a new class of autoantibodies in glomerulonephritis, vasculitis and other inflammatory disorders.

Anti-neutrophil cytoplasmic antibodies (ANCA) constitute a new group of antibodies that are directed against myeloid proteins. Several antigens recognized by ANCA have been described. Antibodies directed to proteinase 3, myeloperoxidase and/or elastase are closely associated with necrotizing systemic vasculitis and/or necrotizing and crescentic glomerulonephritis. Changes in levels of anti-proteinase 3 in generally reflect disease activity in Wegener's granulomatosis. The diagnostic significance of other or still unknown specificities has not yet been definitely established. Recent data from in vitro and in vivo models suggest a role for ANCA in the pathogenesis of systemic vasculitides and/or necrotising and crescentic glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model.

To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO, to the glomerular basement membrane (GBM). Upon immunization rats developed antibodies and positive skin tests to MPO. After unilateral perfusion of the left kidney with the lysosomal enzyme extract and H2O2, MPO and immunoglobulin (Ig)G localized transiently along the GMB. At the time of maximal inflammation, at 4 and 10 d after perfusion, MPO, IgG, and C3 could not be detected anymore. MPO-immunized rats perfused with the lysosomal enzyme extract and H2O2, in contrast to control-immunized and/or control-perfused rats, developed a proliferative GN characterized by intra- and extracapillary cell proliferation, ruptured Bowman's capsule, periglomerular granulomatous inflammation, and formation of giant cells. Monocytes, polymorphonuclear leukocytes (PMN), and to a far lesser extent T cells were found in the glomeruli. Interstitial infiltrates consisted of monocytes, PMN, and T cells. Granulomatous vasculitis of small vessels was found at 10 d after perfusion. The proliferative NCGN in this rat model closely resembles human anti-MPO-associated pauci-immune NCGN, and enables the study of the pathophysiology of anti-MPO-associated NCGN.

Animals↗
PubMed1993

Induction of an humoral and cellular (auto) immune response to human and rat myeloperoxidase(MPO) in Brown-Norway(BN), Lewis and Wistar Kyoto(WKY) rat strains.

Anti-MPO and anti-proteinase 3 antibodies are strongly associated with certain forms of vasculitis and glomerulonephritis and a pathophysiological role for the antibodies has been hypothesized (Kallenberg et al. 1991). To test this hypothesis WKY, Lewis and BN rats were immunized with human MPO. BN rats developed a strong humoral response, cross reacting with autologous MPO, and Lewis rats a strong cellular response to human MPO.

Animals↗
PubMed1993

Anti-neutrophil cytoplasmic antibodies in giant cell arteritis and polymyalgia rheumatica.

Antineutrophil cytoplasmic antibodies (ANCA) were demonstrated in all sera from 11 patients with active giant cell arteritis (GCA) using indirect immunofluorescence on 9% paraformaldehyde(PF)-fixed neutrophils according to Pryzwanski (median titer 1:256, range 1:64 to 1:512). After treatment during inactive disease titers decreased in all sera. Eight out of 9 sera from patients with active polymyalgia rheumatica (PMR) produced a cytoplasmic staining on Pryzwanski-fixed neutrophils in low titers (median titer 1:16, range 0 to 1:32), as did 8 out of 25 sera from healthy blood donors. None of the sera were positive for antibodies to defined antigens, i.e. proteinase-3, human leucocyte elastase, myeloperoxidase and lactoferrin as detected by ELISA. GCA seems to be associated with ANCA of as yet unknown specificity.

Aged↗
PubMed1993

Serum markers of T-cell activation in relapses of Wegener's granulomatosis.

Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T-cell activation in serial serum samples drawn monthly from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1162 U/ml (median, 95% CI 843 to 1814 U/ml) at three months before the relapse to 1684 U/ml (95% CI 1254 to 2202 U/ml) at the time of relapse for the whole group (P = 0.10). The 8 major relapses showed a profound rise in sIL-2R levels (P < 0.01). The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.547, P < 0.05) and with the disease activity score (r = 0.814, P < 0.001). There were no significant changes in levels of sCD4 or sCD8.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Serum markers of T cell activation in relapses of Wegener's granulomatosis.

Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P = 0.10). The eight major relapses showed a profound rise in sIL-2R levels, from 1008 U/ml (median, range 686-1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469-3404 U/ml) at the moment of relapse (P < 0.01). The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (P < 0.05). Minor relapses were not accompanied by a significant rise in sIL-2R levels. Titres of antineutrophil cytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titre and an at least 25% increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month. The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.488, P < 0.05) and with the disease activity score (r = 0.824, P < 0.002). There were no significant changes in levels of sCD4 or sCD8, although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis are accompanied by systemic T cell activation. T cell activation, however, does not appear to precede the rise in ANCA titre.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Occurrence of autoantibodies to human leucocyte elastase in Wegener's granulomatosis and other inflammatory disorders.

Antineutrophil cytoplasmic antibodies (ANCAs) constitute a new class of autoantibodies that seem to recognise myeloid lysosomal enzymes. The occurrence of ANCAs with specificity for human leucocyte elastase (HLE) was assessed in serum samples that were routinely submitted for ANCA determination. During a study period of more than six years anti-HLE was found in only six out of 1102 serum samples that produced a perinuclear or an atypical cytoplasmic staining pattern on ethanol fixed granulocytes. These six serum samples were from four patients with a clinical diagnosis of Wegener's granulomatosis but without a definite histological diagnosis, one patient with systemic vasculitis, and one patient with Cogan's syndrome. To further evaluate the prevalence of anti-HLE we tested 315 serum samples from patients with different forms of vasculitis and related disorders. Anti-HLE was detected in two patients only. Thus autoantibodies to HLE are rarely found in serum samples from patients with vasculitic or related disorders.

Aged↗