PubMed Health⌕ Search

Biomedical subjects

C F Franssen

Publications and source records attributed to C F Franssen.

15 recordsLinked to original sources
PubMed2000

In vitro T lymphocyte responses to proteinase 3 (PR3) and linear peptides of PR3 in patients with Wegener's granulomatosis (WG).

T cell-mediated immunity is thought to play an important role in the pathogenesis of WG. In previous studies a minority of WG patients as well as some healthy controls showed in vitro proliferation of their peripheral blood mononuclear cells (PBMC) to PR3, the main autoantigen in WG. The relevant peptides responsible for this in vitro proliferation have not been identified. In order to define immunogenic peptides, PBMC of 13 WG patients in remission and 10 healthy controls were tested for proliferation to linear peptides of PR3 and to whole PR3. Fifty overlapping peptides spanning the whole PR3 sequence were synthesized. Peptides were tested in pools of five peptides and as single peptide. PBMC of two WG patients and one healthy control proliferated to whole PR3 and to peptide pools. In addition, 10 WG patients and eight healthy controls that did not proliferate to whole PR3 did proliferate to pools of PR3 peptides. Although more WG patients tended to react to particular peptide pools, no significant difference was seen between lymphocyte proliferation to PR3 peptides of WG patients and that of healthy controls. The pools of peptides recognized were mainly located at the N- and C-terminus of PR3. No correlation was observed between HLA type and proliferation on particular peptide pools. No proliferation of PBMC was observed to single peptides. In conclusion, T cells of WG patients proliferate in vitro more frequently to PR3 peptides than to the whole PR3 protein. Peptides derived from the signal sequence, the propeptide or peptides located at the C-terminus of PR3 induce highest levels of proliferation. No specific PR3 sequence could be identified that was preferentially recognized by PBMC of WG patients compared with controls.

Adult↗
PubMed2000

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis.

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Wegener's granulomatosis, microscopic polyangiitis, and idiopathic pauci-immune necrotizing crescentic glomerulonephritis (NCGN) are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against either proteinase 3 (anti-PR3) or myeloperoxidase (anti-MPO). This has led some investigators to prefer combining these diseases under the common heading of ANCA-associated vasculitides. However, it is increasingly recognized that there are characteristic differences between patients with anti-PR3 and those with anti-MPO-associated vasculitis. This review focuses on the clinical, histopathologic, and possibly pathophysiologic differences between anti-PR3- and anti-MPO-associated vasculitis. Although there is considerable overlap, the anti-PR3- and anti-MPO-associated vasculitides are each characterized by particular clinical and histopathological findings. Extrarenal organ manifestations and respiratory tract granulomas occur more frequently in patients with anti-PR3 than in those with anti-MPO. Anti-PR3-positive patients with NCGN generally have a more dramatic deterioration of their renal function compared with anti-MPO-positive patients. The term "ANCA-associated vasculitis" is considered as a useful concept in the presence of systemic vasculitis. Likewise, in the presence of vasculitis, the terms "anti-PR3-associated vasculitis" and "anti-MPO-associated vasculitis" are useful concepts.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Hemolytic uremic syndrome due to Capnocytophaga canimorsus bacteremia after a dog bite.

The hemolytic uremic syndrome (HUS) is known to have several causes, including infectious diseases, drugs, pregnancy, and malignant disease. We report a patient who developed acute renal failure attributable to HUS in the course of Capnocytophaga canimorsus bacteremia. Acute tubular necrosis as well as HUS should be considered as a cause of acute renal failure in the setting of Capnocytophaga canimorsus bacteremia.

Animals↗
PubMed1999

In vitro neutrophil activation by antibodies to proteinase 3 and myeloperoxidase from patients with crescentic glomerulonephritis.

Previously, it was found that patients with necrotizing crescentic glomerulonephritis (NCGN) and anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against proteinase 3 (anti-PR3) had a faster deterioration of renal function and more active renal vasculitic lesions than patients with ANCA directed against myeloperoxidase (anti-MPO). Because ANCA-mediated neutrophil activation is thought to play an important role in the pathophysiology of this form of glomerulonephritis, this study was conducted to determine whether anti-PR3 are capable of inducing a more pronounced activation of neutrophils in vitro than anti-MPO. To test this hypothesis, the release of reactive oxygen radicals, as assessed by ferricytochrome c reduction and by dihydrorhodamine 123 oxidation, and the release of granule constituents from healthy donor neutrophils upon stimulation with IgG fractions were measured from 17 anti-PR3- and 14 anti-MPO-positive patients with active NCGN. Patients with anti-PR3 had a higher renal activity index (P < 0.05) compared with patients with anti-MPO. IgG fractions from anti-PR3-positive patients induced more oxygen radical release from tumor necrosis factor-alpha-primed neutrophils compared with IgG fractions from anti-MPO-positive patients, as assessed by ferricytochrome c reduction (P < 0.05) and dihydrorhodamine 123 oxidation (P < 0.01). In addition, IgG fractions from anti-PR3-positive patients generated more neutrophil degranulation of beta-glucuronidase (P < 0.01) than IgG fractions from anti-MPO-positive patients. In conclusion, IgG fractions from anti-PR3-positive patients with NCGN are more potent activators of the respiratory burst and degranulation in vitro than IgG fractions from anti-MPO-positive patients. These observations may be relevant in view of the clinical differences between anti-PR3- and anti-MPO-positive patients with NCGN.

Adult↗
PubMed1998

Determinants of renal outcome in anti-myeloperoxidase-associated necrotizing crescentic glomerulonephritis.

Patients with anti-myeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN) may develop chronic renal failure (CRF) leading to end-stage renal disease despite an initially favorable response to treatment. The aim of this study was to determine the prognostic value of clinical, laboratory, and histopathologic features at the time of presentation and during follow-up for the development of CRF in 21 consecutive anti-MPO-positive patients with NCGN. Renal function did not recover in two of five patients who were dialysis-dependent at presentation. The remaining 19 patients all went into remission and were off dialysis at 3 mo after diagnosis. At long-term follow-up, nine of these patients had stable renal function and did not relapse (group A), five patients developed CRF without signs of relapse (group B), and five patients relapsed (group C). At diagnosis, serum creatinine, C-reactive protein, and anti-MPO levels did not differ between groups A, B, and C. Microscopic erythrocyturia resolved in all patients within 4 mo of treatment. BP at presentation and during follow-up did not differ between groups A, B, and C. Proteinuria at diagnosis and in the first 6 mo after diagnosis was higher in patients who developed CRF than in patients with a stable renal function. Anti-MPO levels at 3 mo had decreased compared with anti-MPO levels at diagnosis in groups A and C, whereas anti-MPO levels did not fall significantly in patients who developed CRF. The predictive value of a renal biopsy at diagnosis on long-term renal outcome was limited. In conclusion, a higher degree of proteinuria at diagnosis and during follow-up as well as persistently elevated anti-MPO levels after induction of remission are associated with the development of CRF and are predictive of poor renal outcome in anti-MPO-associated NCGN.

Adrenal Cortex Hormones↗
PubMed1996

Hydralazine-induced constrictive pericarditis.

A 59-year-old man was diagnosed as having constrictive pericarditis 17 months after a typical hydralazine-induced autoimmune syndrome. This late complication of hydralazine has been reported only once. Ten years later the patient was found to have anti-neutrophil cytoplasmic antibodies directed against myeloperoxidase.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Respiratory failure in ANCA-associated vasculitis.

OBJECTIVE: To assess the prevalence, clinical manifestations, and course of respiratory failure in all patients who tested positive for antineutrophil cytoplasmic autoantibodies (ANCA) in our clinics in the period between January 1985 and January 1993. DESIGN: Case-series analysis. SETTING: Three teaching hospitals in the Netherlands. PATIENTS: Two hundred twenty consecutive patients suspected of having vasculitis and/or glomerulonephritis who tested positive for ANCA by indirect immunofluorescence and enzyme-linked immunosorbent assay. RESULTS: Sixty-two patients had pulmonary involvement. Acute respiratory failure developed in nine. Respiratory failure was related to infections in two of them and to ANCA-associated vasculitis in seven. These seven patients uniformly presented with pulmonary hemorrhage and diffuse pulmonary infiltrates. The diagnosis of systemic vasculitis was supported by the presence of a pulmonary-renal syndrome in all patients, and by detection of antibodies to the proteinase 3 or myeloperoxidase antigen in all but one patient. Antiglomerular basement membrane antibodies were absent. The mortality was high due to hypoxic respiratory failure, pulmonary superinfections, and concomitant renal failure. CONCLUSIONS: Acute respiratory failure due to vasculitis developed in one of every nine patients with ANCA-associated pulmonary disease. Patients usually present with pulmonary infiltrates and hemoptysis. A diagnosis of vasculitis may be further supported by analysis of the urinary sediment and determination of the ANCA target antigen. It remains to be proved that early detection of ANCA favorably affects the outcome.

Adult↗
PubMed1995

Differences between anti-myeloperoxidase- and anti-proteinase 3-associated renal disease.

We performed a retrospective study of the clinical features, the pattern of the pre-treatment renal function loss, the renal morphology and the outcome in 92 patients with anti-neutrophil cytoplasmic autoantibodies directed against proteinase 3 (aPR3; N = 46) or myeloperoxidase (aMPO; N = 46). Patients with aMPO had a higher median age than patients with a PR3 (63 and 56 years; P < 0.05). The mean (+/- SD) number of affected organs in the aPR3 group exceeded that of the aMPO group (3.9 +/- 1.4 and 2.2 +/- 1.1; P < 0.01). The prevalence of renal involvement did not differ between patients with aPR3 and aMPO (83% and 67%, respectively; NS). Pre-treatment renal function deteriorated significantly faster in aPR3- than in aMPO-associated renal disease. The kidney biopsies from patients with aPR3 showed a higher activity index (10.2 +/- 3.8 and 7.3 +/- 3.2; P < 0.03) and a lower chronicity index (4.5 +/- 2.6 and 7.0 +/- 3.1; P < 0.02) than biopsies from patients with aMPO. The kidney survival at two years was 73% in patients with aPR3- and 61% in patients with aMPO-associated renal disease (NS). We conclude that renal function generally deteriorates faster in aPR3- than in aMPO-associated renal disease. This goes together with more active renal lesions in patients with aPR3 and more chronic renal lesions in patients with aMPO. Despite these differences, there is no difference in outcomes between both antibody groups.

Adult↗
PubMedDate not supplied

In vitro up-regulation of E-selectin and induction of interleukin-6 in endothelial cells by autoantibodies in Wegener's granulomatosis and microscopic polyangiitis.

OBJECTIVE: In patients with Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA) autoantibodies to myeloid granule proteins (ANCA), particularly proteinase 3 (Pr3) and myeloperoxidase (MPO), and to endothelial cells (AECA) are frequently detected. The role of these autoantibodies in the development of vascular injury is incompletely understood. Since the expression of E-selectin and the production of interleukin 6 by endothelial cells is an early step in the sequence of events leading to vascular injury, we examined the capacity of IgG fractions from patients with WG and/or MPA to activate endothelial cells to the expression of E-selectin and the production of IL-6. We related those findings to the presence of ANCA and AECA in the IgG preparations. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with immunoglobulin (IgG) preparations from 28 patients (17 positive for anti-Pr3, 10 for anti-MPO, and one for anti-Pr3/MPO) with active vasculitis and from 10 healthy volunteers. The final IgG concentration in the activation assay was 2 mg/ml. TNF alpha (10 ng/ml) and LPS (10 ng/ml) were used as positive controls for HUVEC activation. The extent of HUVEC activation was assessed by the measurement of E-selectin expression by flow cytometry (after 4 hours of incubation) and the production of interleukin 6 by ELISA (after 24 hours). RESULTS: We found that 11 of the 28 ANCA positive IgG samples were capable of activating endothelial cells: six samples induced IL-6 production alone, one sample upregulated E-selectin expression alone, and four samples induced both IL-6 production and E-selectin upregulation. Five of 17 anti-Pr3 positive samples (one of which was also positive for AECA) and 6 of 10 anti-MPO positive samples (all simultaneously positive for AECA) induced endothelial cell activation. AECA positive samples that induced endothelial cell activation (n = 7) had higher AECA titres than samples that did not induce endothelial cell activation (n = 6). CONCLUSION: Our data suggest that the activation of endothelial cells in patients with WG and MPA can be induced by circulating autoantibodies. Both ANCA and AECA can be responsible for this effect.

Adolescent↗