Biomedical subjects

F J Van Der Woude

Publications and source records attributed to F J Van Der Woude.

13 recordsLinked to original sources

PubMed2005

Altered CD46-mediated T cell co-stimulation in haemodialysis patients.

While most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28-CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD (n = 9), peritoneal dialysis (PD) (n = 10) and predialysis patients (n = 8) compared to healthy controls (HC) (n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4(+)T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4(+)T cells was found (64% +/- 21%versus 23% +/- 18%, P < 0.001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after co-stimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4(+)T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity.

Aged↗

PubMed2005

Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis.

In patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4(+) CD25(+) T-regulatory-cells (T(reg)) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in T(reg) cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4(+) cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). In addition, T cell proliferation and cytokine secretion after stimulation with anti-CD3 and anti-CD28 and intracellular cytokine production after stimulation with phorbol myristate acetate (PMA)-ionomycin was determined. Controls were non-vasculitic renal transplant patients (n = 9) and healthy controls (HC) (n = 13). In AAV the total number of lymphocytes, CD4(+) lymphocytes and the percentage of naive T cells are lower than in HC and RTX. An increased percentage of CD25(+) cells was found in AAV and AAV/RTX, irrespective of disease activity, but not in HC or RTX. This was confined to the naive (CD4(+) CD45RB(high)) population only. FOXP3 mRNA expression in CD4(+) T cells did not differ between AAV patients and healthy controls. In vitro T cell proliferation was enhanced in AAV patients compared to HC (P < 0.01). PBMC of AAV patients produced significantly less interleukin (IL)-10 and interferon (IFN)-gamma after anti-CD3/CD28 stimulation. The percentage of IL-10 and IL-12, but not IFN-gamma, IL-4 or tumour necrosis factor (TNF)-alpha-producing cells was significantly higher in patients compared to HC. These findings were confined to the memory population of CD4(+) cells. We conclude that AAV patients are lymphopenic and have low numbers of CD4(+) T cells, which seem to be in a persistent state of activation.

Adult↗

PubMed2003

[Rapidly progressive glomerulonephritis:classification, pathogenesis and clinical management].

Rapidly progressive glomerulonephritides (RPGN) belong to a heterogeneous group of inflammatory kidney diseases which are commonly associated with systemic vasculitic syndromes. Renal histology is characterized by necrotizing lesions within the glomerual tuft and extracapillary proliferation, in most cases leading rapidly to renal failure. The etiology and pathogenesis are only partly elucidated. Since irreversible renal scaring develops within days to weeks, RPGN represent a nephrological emergency necessitating urgent diagnostic evaluation and rapid institution of effective therapy. New onset nephritic sediment combined with concomitantly deteriorating excretory renal function should lead to immediate nephrological consultation. Autoimmune serology and particularly renal biopsy are of the utmost importance for rapid diagnosis. Most forms of RPGN are treated with immunosuppressive regimens which generally consist of high dose steroids in combination with the alkylating agent cyclophosphamide. Some forms also require the use of plasma exchange therapy. Rapid diagnosis and early therapy improves both renal and overall outcome in the affected patients.

Diagnosis, Differential↗

PubMed2003

Effects of anti-neutrophil cytoplasm autoantibodies on tissue factor activity by HL-60 cells in vitro.

The effects of cytoplasmic anti-neutrophil cytoplasm autoantibodies (C-ANCA) and perinuclear ANCA (P-ANCA) immunoglobulin G (IgG) on tissue factor (TF) activity using HL-60 cells in vitro were compared with those of medium, lipopolysaccharide (LPS) and control IgG. Cells were also incubated with both ANCA IgG and control IgG in the presence of a submaximal concentration of LPS capable of upregulating TF procoagulant activity (TF-PCA) measured in arbitrary units of TF equivalent (AU-TFEq). The purpose was to search for an additive effect between LPS and ANCA IgG. All IgG preparations increased HL-60 cell TF-PCA in comparison with the medium. When cells were incubated with P-ANCA IgG and LPS (1 micro g/ml), a larger increase was seen (151.23 +/- 31.6 SEM (standard error of the mean) AU-TFEq) than when incubated with control IgG plus LPS (91.01 +/- 18.4 SEM AU-TFEq; P < 0.005), P-ANCA IgG alone (73.68 +/- 12.7 SEM AU-TFEq; P < 0.005) or LPS (1 micro g/ml) (58.11 +/- 7.9 SEM AU-TFEq; P < 0.005). There was concordance between PCA and TF total antigen content by enzyme-linked immunosorbent assay (ELISA). The fact that P-ANCA IgGs upregulate the function of TF in HL-60 cells in combination with LPS adds to information regarding the possible role of ANCAs in the enhancement of TF by different cells, although it does not support the fact that ANCAs alone play a role in mononuclear cell TF upregulation. The additive effects of LPS underline the possible role of pro-inflammatory stimuli in the pathogenesis of ANCA-associated diseases.

Adult↗

PubMed2000

Dopamine induces the expression of heme oxygenase-1 by human endothelial cells in vitro.

BACKGROUND: In a retrospective study of the kidney transplantations performed at our institution, we found that the administration of dopamine (DA) to the organ donors resulted in a significant improvement of long-term organ survival of the retrieved kidneys. To study the mechanisms underlying the organ protection associated with the administration of DA prior to transplantation, we questioned whether DA induces the antioxidative enzyme heme oxygenase-1 (HO-1) in cultured endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) in culture were incubated with varying concentrations of DA for different time periods. Cells were subsequently assessed for the expression of HO-1 by Western blot and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The presence of DA resulted in a dose- and time-dependent up-regulation of HO-1 both on RNA and protein level, whereas HO-1 was barely detectable under basal conditions. RT-PCR indicated the increased presence of HO-1 messenger RNA after 2 hours of incubation with DA, which peaked after 24 hours. The induction of HO-1 antigen was detectable after eight hours, as visualized by Western blot analysis. The addition of the antioxidant agents ascorbic acid and N-acetyl-cysteine both lead to dose-dependent inhibition of DA-mediated HO-1 induction. DA-mediated up-regulation of HO-1 was not influenced by the addition of either the D2-receptor antagonist haloperidol or the D1-receptor antagonist SCH 23390. CONCLUSION: We conclude that DA induces the expression of the protective enzyme HO-1 in cultured endothelial cells by an oxidative mechanism. These findings may explain the beneficial effect of DA administration to kidney donors and indicate the potential role of DA in organ preconditioning.

Antioxidants↗

PubMed1999

Release of CXC-chemokines by human lung microvascular endothelial cells (LMVEC) compared with macrovascular umbilical vein endothelial cells.

In the present study, the sensitivity of LMVEC and human umbilical vein endothelial cells (HUVEC) to lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was compared. To this end, the production of the CC- (MCP-1), CXC- (IL-8, ENA-78, Groalpha, NAP-2, GCP-2) and CX3C (fractalkine) chemokines was studied. A low basal production of these chemokines was observed in both cell types. TNF-alpha, IL-1 and LPS up-regulated all chemokines tested. IFN-gamma however was only able to up-regulate MCP-1 production. LMVEC were more sensitive to IL-1 and LPS compared with HUVEC, since LMVEC produced significantly more MCP-1, ENA-78 and Groalpha (P < 0. 01) under these conditions. Maximal production of MCP-1 in LMVEC was achieved with TNF-alpha (28.4 ng/ml, P < 0.01), whereas IL-1 was the most potent stimulator of ENA-78 (2.78 ng/ml, P < 0.001) and Groalpha (29.2 ng/ml, P < 0.001). IL-8 production in LMVEC cells was maximal after LPS stimulation (28.4 ng/ml), but lower than on HUVEC (P < 0.01). LPS, TNF-alpha and IL-1 stimulation strongly up-regulated all chemokine mRNA. No quantitative differences in mRNA expression between LMVEC and HUVEC were detected for MCP-1 and Groalpha after LPS stimulation. mRNA expression of ENA-78, GCP-2, CX3C and NAP-2 was however higher in LMVEC under LPS stimulation. In contrast, IL-8 mRNA was slightly more expressed in HUVEC under these conditions. These results further support the hypothesis that the microvascular lung endothelium plays an active role in the induction and perpetuation of acute lung injury.

Cells, Cultured↗

PubMed1999

Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation.

BACKGROUND: Epidemiological data implicate that renal transplants from living unrelated donors result in superior survival rates as compared with cadaveric grafts, despite a higher degree of human lymphocyte antigen (HLA) mismatching. We undertook a center-based case control study to identify donor-specific determinants affecting early outcome in cadaveric transplantation. METHODS: The study database consisted of 152 consecutive cadaveric renal transplants performed at our center between June 1989 and September 1998. Of these, 24 patients received a retransplant. Donor kidneys were allocated on the basis of prospective HLA matching according to the Eurotransplant rules of organ sharing. Immunosuppressive therapy consisted of a cyclosporine-based triple-drug regimen. In 67 recipients, at least one acute rejection episode occurred during the first month after transplantation. They were taken as cases, and the remaining 85 patients were the controls. Stepwise logistic regression was done on donor-specific explanatory variables obtained from standardized Eurotransplant Necrokidney reports. In a secondary evaluation, the impact on graft survival in long-term follow-up was further measured by applying a Cox regression model. The mean follow-up of all transplant recipients was 3.8 years (SD 2.7 years). RESULTS: Donor age [odds ratio (OR) 1.05; 95% CI, 1.02 to 1.08], traumatic brain injury as cause of death (OR 2.75; 95% CI, 1.16 to 6. 52), and mismatch on HLA-DR (OR 3.0; 95% CI, 1.47 to 6.12) were associated with an increased risk of acute rejection, whereas donor use of dopamine (OR 0.22; 95% CI, 0.09 to 0.51) and/or noradrenaline (OR 0.24; 95% CI, 0.10 to 0.60) independently resulted in a significant beneficial effect. In the multivariate Cox regression analysis, both donor treatment with dopamine (HR 0.44; 95% CI, 0.22 to 0.84) and noradrenaline (HR 0.30; 95% CI, 0.10 to 0.87) remained a significant predictor of superior graft survival in long-term follow-up. CONCLUSIONS: Our data strongly suggest that the use of catecholamines in postmortal organ donors during intensive care results in immunomodulating effects and improves graft survival in long-term follow-up. These findings may at least partially be explained by down-regulating effects of adrenergic substances on the expression of adhesion molecules (VCAM, E-selectin) in the vessel walls of the graft.

Acute Disease↗

PubMed1999

Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis.

BACKGROUND: In kidney biopsies of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis, a variety of histopathological lesions occur, and their relationship to renal outcome is virtually unknown. This multicenter European study reports a clinicopathological analysis of biopsies from 157 patients with systemic vasculitis. METHODS: The biopsies were evaluated according to a previously standardized scoring protocol. Serum creatinine values were measured at the time of biopsy and one year later. In addition, the lowest creatinine level during follow-up was taken into account as the optimum level of renal function recovery. The clinical prognostic value of the histopathological parameters was analyzed with the Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U-test. RESULTS: The percentage of normal glomeruli correlated most significantly with renal outcome at all points of measurement (all P < 0.001). Other lesions predicting for renal function were glomerular sclerosis (P < 0.0005 at one year after the biopsy), diffuse interstitial infiltrates (P < 0.0001 at entry, P < 0.0003 at one year), tubular necrosis (P < 0.0025 at entry), and tubular atrophy (P < 0.002 at entry, P < 0.0002 at one year). CONCLUSION: Traditionally, attention is focused on the extent of active lesions in the renal biopsy in order to determine the severity of renal disease and its implication for renal outcome. Because of their significant impact on renal function, combined with their easy recognition, we recommend the use of the percentage of normal glomeruli in an adequate biopsy in predicting renal function of patients with systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1998

Impact of renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up.

Despite a superior quality of life and a favorable cost effectiveness, it has not been well established thus far whether renal cadaveric transplantation contributes to superior survival probability of end-stage renal disease patients in Europe, because the mortality rate on dialysis is lower compared with the United States. This analysis was undertaken to compare the mortality of wait-listed patients and transplant recipients during long-term follow-up, including the possibility of a retransplant in a single-center study. The study cohort included 309 consecutive patients, ages 17 to 72 yr, being registered on the waiting list of the Renal Transplantation Center of Mannheim since the initiation of the transplantation program on June 3, 1989. Follow-up was terminated on September 30, 1997, with a mean of 4.15 yr. A total of 144 renal cadaveric transplants (four retransplants) was performed during the follow-up period. A Cox regression model considering the time-dependent exposure to the different therapy modalities was applied for statistical analysis. Patients being removed from the waiting list or coming back to dialysis after transplantation were censored at time of withdrawal or graft failure. Transplantation resulted in a lower hazard ratio, which was 0.36 (95% confidence interval, 0.15 to 0.87) when the hazard of the wait-listed group was taken as 1.00. The underlying incidence rate of death was 0.026 per patient-year (0.032 on dialysis versus 0.016 with functioning graft). Performing the evaluation on an intention-to-treat basis without censoring the lower risk of the transplanted group was still pronounced according to a hazard ratio of 0.44 (95% confidence interval, 0.22 to 0.89). Thus, patients receiving a renal cadaveric transplantation have a substantial survival advantage over corresponding end-stage renal disease patients on the waiting list even in the setting of a single transplantation center where mortality on regular dialysis therapy was comparatively low.

Adolescent↗

PubMed1998

Synergistic effect of IL-1alpha, IFN-gamma, and TNF-alpha on RANTES production by human renal tubular epithelial cells in vitro.

Interstitial rejection of renal allografts is associated with infiltrating mononuclear cells. Mechanisms leading to this mononuclear cell influx are still not fully resolved. The chemokine RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) is chemotactic for monocytes and T cells. In renal allograft biopsies of patients undergoing rejection, RANTES is found in infiltrating monocytes and T cells, as well as in the tubular epithelium. This study analyzes the production of RANTES in vitro by proximal tubular epithelial cells (PTEC) after stimulation with the inflammatory cytokines interleukin-1alpha, (IL-1alpha), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). Unstimulated PTEC or PTEC stimulated with the cytokines IL-1alpha, IFN-gamma, and TNF-alpha alone did not produce detectable amounts of RANTES. However, a combination of IFN-gamma and either IL-1alpha or TNF-alpha resulted in strong induction of RANTES production up to 2046 +/- 817 pg/ml or 2595 +/- 525 pg/ml per 1 x 10(5) PTEC, respectively. After stimulation with IL-1alpha and TNF-alpha, RANTES production was less prominent than the combination of IFN-gamma with either IL-1alpha or TNF-alpha, and only detectable in 5 of 7 PTEC lines tested. The production of RANTES was both dose- and time-dependent and was inhibited by cycloheximide, indicating that de novo protein synthesis is required. Because the production of RANTES by PTEC is more pronounced in the presence of T cell-derived IFN-gamma (in combination with either IL-1alpha or TNF-alpha), it was hypothesized that RANTES produced by PTEC presumably plays a prominent role in the amplification phase of the immune response rather than in the initiation phase.

Antibodies↗

PubMed1996

The risk of skin cancer in renal transplant recipients in Queensland, Australia. A follow-up study.

A long-term retrospective follow-up study was performed to evaluate the risk of skin cancer in 1098 renal transplant recipients in Queensland, Australia. In a subgroup, we also assessed the influence of immunosuppressive therapy on the risk of developing skin cancer: cyclosporine alone or in combination with prednisolone; azathioprine alone or in combination with prednisolone; or the combination of cyclosporine and azathioprine with or without prednisolone. The cumulative incidence of developing skin cancer, calculated by life table analysis, increased progressively from 7% after 1 year of immunosuppression to 45% after 11 years and to 70% after 20 years of immunosuppression. Multivariate analysis in a subgroup comparing the risk of developing skin cancer in patients on either long-term cyclosporine or azathioprine (each with or without prednisolone) and in patients on the combination of cyclosporine and azathioprine (with or with- out prednisolone) showed no differences between the groups. We conclude that it is likely that the increased risk of skin cancer associated with immunosuppression is independent of the agent(s) used and is a result of the immunosuppression per se.

Adolescent↗

PubMed1996

1,25-dihydroxycholecalciferol enhances the expression of MHC class II antigens and intercellular adhesion molecule-1 by human renal tubular epithelial cells.

PURPOSE: Beside its role in calcium and phosphorus metabolism, 1,25-dihydroxycholecalciferol (1,25-D3) exerts multiple effects on cytokine and major histocompatibility complex (MHC) class II expression in monocytes and lymphocytes. In different renal diseases tubular epithelial cells express MHC class II molecules and cell adhesion molecules,, such as intracellular adhesion molecule-1 (ICAM-1). Therefore, modulation of MHC class II and ICAM-1 expression in renal tubular epithelial cells by 1,25-D3 may be relevant to lymphocyte adhesion to tubular epithelial cells and immune mediated renal injury. However, the expression of MHC class II antigens and cellular adhesion molecules by renal tubular epithelial cells in response to 1,25-D3 has not been investigated. MATERIALS AND METHODS: We generated human renal tubular epithelial cells and SV40 transfected tubular epithelial cells to investigate immune modulation of 1,25 on renal epithelial cells. Major histocompatibility complex class II molecules and ICAM-1 were detected by a specific enzyme linked immunoassay. RESULTS: We found a dose-dependent increase of both constitutive and induced MHC class II and ICAM-1 expression in tubular epithelial cells stimulated with 1,25-D3. Dose-dependent stimulation of MHC class II and ICAM-1 expression was not restricted to primary human renal tubular epithelial cells but was also detected in SV40 transfected cells. CONCLUSIONS: Expression of MHC class II and ICAM-1 is crucial for antigen presentation by and lymphocyte adhesion to renal tubular epithelial cells. Modulatory effects of 1,25-D3 on immune accessory function of renal tubular epithelial cells may be of clinical significance in renal diseases.

Calcitriol↗

PubMed1991

On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients.

Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens.

Alleles↗