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Biomedical subjects

G T Rijkers

Publications and source records attributed to G T Rijkers.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-8 CSF levels predict survival in patients with leptomeningeal metastases.

Median survival of patients with leptomeningeal metastases (LM) is 4 to 6 months, with a few long-term survivors. Current prognostic factors for survival have limited value. The authors measured the CSF levels of nine inflammatory proteins in 57 patients with LM and determined their prognostic value. High interleukin (IL)-8 CSF levels predicted short-term survival independently. The data indicate that IL-8 CSF levels may serve as a prognosticator in patients with LM, but prospective validation is needed.

Adult↗
PubMed2006

Association of CD14 promoter polymorphism with otitis media and pneumococcal vaccine responses.

Innate immunity is of particular importance for protection against infection during early life, when adaptive immune responses are immature. CD14 plays key roles in innate immunity, including in defense against pathogens associated with otitis media, a major pediatric health care issue. The T allele of the CD14 C-159T polymorphism has been associated with increased serum CD14 levels. Our objective was to investigate the hypothesis that the CD14 C-159T allele is protective against recurrent acute otitis media in children. The association between the CD14 promoter genotype and the number of acute otitis media episodes was evaluated both retrospectively and prospectively in a cohort of 300 children. Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal vaccinations were examined according to CD14 genotype to compare immune responsiveness across genotypes. An age-dependent association was found: compared with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had fewer episodes of acute otitis media (79 versus 41%, respectively; P = 0.004); this relationship was absent in older children. Additionally, TT homozygotes showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data suggest that genetic variation in CD14, a molecule at the interface of innate and adaptive immune responses, plays a key role in the defense against middle ear disease in childhood and in pneumococcal vaccine responsiveness. These findings are likely to be important to these and other immune-mediated outcomes in early life.

Age Factors↗
PubMed2005

[Increase in the number of invasive Haemophilus influenzae type b infections].

OBJECTIVE: To describe the increase of invasive Haemophilus influenzae type b (Hib) infections in The Netherlands before and after the introduction of Hib vaccination in 1993, and to hypothesise about possible explanations. DESIGN: Descriptive. METHOD: Data on the prevalence of invasive Hib infections, such as meningitis and epiglottitis, during 1990-2004 were obtained from The Netherlands Reference Laboratory for Bacterial Meningitis, which collects Hib isolates from spinal fluid and blood from across the country. RESULTS: The incidence of invasive Hib infections decreased substantially for a few years after 1993. The total number of isolates was at a minimum in 1999 (n = 12) and increased to 49 in 2004. The annual number of patients with vaccine failure was 5 or less during 1995-2001, but was between 10 and 15 from 2002 onwards. A definite explanation for the increase in the incidence of invasive Hib infections cannot be given. Improbable causes are a surveillance artefact, an impaired response to the vaccine due to vaccination-scheme changes or interaction with other vaccines, or selection of Hib variants that are less sensitive to the vaccine-induced immunity. It most likely involves secondary vaccine failure: Hib carriership is decreased by mass vaccination, whereupon natural boosting occurs less frequently later in life. Subsequently, immunity decreases and susceptibility to invasive infection increases. Careful surveillance of invasive Hib infections in The Netherlands remains important.

Bacterial Capsules↗
PubMed2005

Pneumococcal conjugate vaccination does not induce a persisting mucosal IgA response in children with recurrent acute otitis media.

AIM: In a prospective controlled study in young children with a history of recurrent acute otitis media, we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine (PCV) given once or twice, followed by a 23-valent polysaccharide booster vaccination. METHODS: Salivary IgA and IgG antibody concentrations to vaccine serotype 6B, 14, 18C and 19F were measured by enzyme immunoassay in 38 samples of children vaccinated with PCV and 45 control samples. In the PCV group, 12 samples were taken prior to vaccination, 12 samples 4 weeks after the polysaccharide booster (8 months after the first conjugate vaccination) and 14 samples 7 months after the last vaccination (14 months after the first conjugate vaccination). In the control group 15 children were sampled at each of these three time points. RESULTS: We observed an increase in salivary IgG antibody concentrations against serotype 6B, 14, and 18C 14 months after the primary vaccination in children vaccinated with PCV twice, although this was significant for serotype 14 only. There was no increase in salivary IgG antibody in children vaccinate with PCV once nor in control children. IgA antibody titers increased significantly after 8 and after 14 months in both the pneumococcal vaccine recipients and the controls. However, the observed increase in mean antibody titers was significantly higher in control children compared to the PCV group. CONCLUSION: We suggest that repeated pneumococcal conjugate vaccination is necessary to induce an increase in salivary IgG antibodies and effectuate clearance of S. pneumoniae from the nasopharyngeal mucosa of children with recurrent acute otitis media. We hypothesize that the increase in salivary IgA is caused by the local boosting of the mucosal immune response by carriage and recurrent infections, which occurs less often in the PCV group compared to the control children.

Child↗
PubMed2005

The role of airway epithelium and blood neutrophils in the inflammatory response in cystic fibrosis.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which accounts for the cAMP-modulated chloride conductance of airway epithelial cells. CFTR also regulates other membrane proteins like the negative regulation of the amiloride-sensitive epithelial sodium channel (ENaC). Mutations in the CFTR gene lead to hyperabsorption of sodium chloride and a reduction in the periciliary salt and water content which leads to impaired mucociliary clearance. It seems that a lack of functional CFTR leads to abnormal function of the NF-kappaB pathway in submucosal gland cells, causing an increased production of pro-inflammatory cytokines and the chemokine IL-8, and a pro-inflammatory environment. CFTR is also expressed in neutrophils and several neutrophil functions like cytokine production, migration, phagocytosis and apoptosis seem altered in CF. In this review we describe the role of airway epithelium and blood neutrophils in the viscious circle of inflammation and infection seen in CF.

Animals↗
PubMed2005

Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines.

BACKGROUND: Decreased exposure to microbial stimuli has been proposed to be involved in the increased prevalence of atopic disease. Such a relationship was indicated by enhanced presence of typical probiotic bacteria in the intestinal flora correlating with reduced prevalence of atopic disease. Recent clinical trials suggested that probiotic bacteria may decrease and prevent allergic symptoms, but which (different) species or strains may contribute is poorly understood. OBJECTIVE: We sought to select probiotic bacteria by their ability to modulate in vitro production of cytokines by peripheral blood mononuclear cells (PBMCs), to make a rational choice from available strains. METHODS: PBMCs, purified monocytes, and lymphocytes from healthy donors were co-cultured with 13 different strains of probiotic bacteria. The effect of lactic acid bacteria (LAB) on different cell populations and effects on cytokine production induced by the polyclonal T cell stimulator phytohaemagglutinin (PHA) was evaluated by measuring T helper type 1, T helper type 2 (Th2), and regulatory cell cytokines in culture supernatants by multiplex assay. RESULTS: PBMCs cultured with different strains produced large amounts of IL-10 and low levels of IL-12p70, IL-5, and IL-13. In PHA-stimulated PBMC cultures, the tested strains decreased the production of Th2 cytokines. Neutralizing IL-10 production resulted in partial to full restoration of Th2 cytokine production and concurred with an increase in pro-inflammatory cytokines such as IL-12p70 and TNF-alpha. Within the PBMCs, the CD14(+) cell fraction was the main source of IL-10 production upon interaction with LAB. CONCLUSION: Our results indicate that certain strains of lactobacilli and bifidobacteria modulate the production of cytokines by monocytes and lymphocytes, and may divert the immune system in a regulatory or tolerant mode. These specific strains may be favorable to use in prevention or treatment of atopic disease.

Adult↗
PubMed2005

Complement dependency of splenic localization of pneumococcal polysaccharide and conjugate vaccines.

The immune response to polysaccharides is initiated when polysaccharides bind complement factor C3d, and these polysaccharide-C3d complexes subsequently localize on splenic marginal zone B cells strongly expressing CD21 (complement receptor 2). Infants and children under the age of 2 years have low or absent expression of CD21 on their marginal zone B cells, and consequently do not adequately respond to polysaccharides. In contrast, polysaccharide-protein conjugate vaccines are able to induce antibodies at this young age. Conjugate vaccines apparently overcome the necessity for CD21-C3d interaction for an antipolysaccharide immune response. We demonstrate in a rat model that localization of pneumococcal polysaccharides on splenic marginal zone B cells indeed is complement dependent. We also show that pneumococcal conjugates do not specifically localize on splenic marginal zone B cells and that splenic localization of polysaccharide conjugates is independent of the presence of complement. Thus, the induction of antipolysaccharide antibodies by conjugate vaccines apparently can occur independently of CD21-C3d interaction. These basic findings may explain the effectiveness of conjugated vaccines in young children and may open the way for their application in other patient groups.

Animals↗
PubMed2005

Molecular epidemiology of pneumococcal colonization in response to pneumococcal conjugate vaccination in children with recurrent acute otitis media.

A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotype distribution was clearly observed (R. Veenhoven et al., Lancet 361:2189-2195, 2003). We investigated the molecular epidemiology of 921 pneumococcal isolates retrieved from both the pneumococcal vaccine (PV) and control vaccine (CV) groups during the vaccination study. Within individuals a high turnover rate of pneumococcal restriction fragment end labeling genotypes, which was unaffected by vaccination, was observed. Comparison of the genetic structures before and after completion of the vaccination scheme revealed that, despite a shift in serotypes, there was clustering of 70% of the pneumococcal populations. The remaining isolates (30%) were equally observed in the PV and CV groups. In addition, the degree of genetic clustering was unaffected by vaccination. However, within the population genetic structure, nonvaccine serotype clusters with the serotypes 11, 15, and 23B became predominant over vaccine-type clusters after vaccination. Finally, overall pneumococcal resistance was low (14%), and, albeit not significant, a reduction in pneumococcal resistance as a result of pneumococcal vaccination was observed. Molecular surveillance of colonization in Dutch children shows no effect of pneumococcal conjugate vaccination on the degree of genetic clustering and the genetic structure of the pneumococcal population. However, within the genetic pneumococcal population structure, a clear shift toward nonvaccine serotype clusters was observed.

Acute Disease↗
PubMed2005

Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology.

As a defective anti-polysaccharide response can exist in the absence of an immunoglobulin deficiency, a series of 26 patients with bronchiectasis of unknown aetiology was vaccinated with a 23-valent pneumococcal polysaccharide vaccine. All patients suffered from recurrent respiratory tract infections. When measuring total antibody levels to pneumococcal serotypes 3, 4 and 9, a normal polysaccharide antibody response was found in 22 patients. However, only 11 of these subjects showed a normal pneumococcal antibody response within the IgA and/or IgG2 subclass, and thus could be classified as true responders, while 15 patients did not respond in either the IgA class or in the IgG2 subclass. When analysing differences between the responder (n = 11) and nonresponder (n = 15) groups, the latter demonstrated higher frequencies of respiratory tract infections and more severe lung pathology, as revealed by the presence of more bronchi visualised in the peripheral third of the lung by high-resolution computed tomography scanning. Moreover, nonresponders needed extensive lung surgery more often in order to control their disease (number of resected segments eight versus five). In conclusion, an important fraction of patients presenting with idiopathic bronchiectasis is associated with a selective anti-polysaccharide response deficiency and this subgroup appears to represent a more severe clinical phenotype. Therefore, it can be regarded as a separate clinical entity with possible therapeutic targets. In order to identify IgA and IgG2 anti-polysaccharide nonresponders, all patients presenting with bronchiectasis of unknown aetiology should be immunised with a pneumococcal polysaccharide vaccine, and IgA and IgG2 isotype responses should be evaluated as well as the total antibody response.

Bronchiectasis↗
PubMed2003

The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat-shock protein 60 capable of producing the regulatory cytokine interleukin-10.

OBJECTIVE: To test the hypothesis that T cell reactivity to self heat-shock protein 60 (Hsp60) in patients with remitting juvenile idiopathic arthritis (JIA) is part of an antiinflammatory, regulatory mechanism. METHODS: Using peripheral blood-derived mononuclear cells (PBMCs) and synovial fluid-derived mononuclear cells (SFMCs) obtained from patients with JIA, we analyzed the expression of CD30 and the induction of regulatory cytokines in response to human and mycobacterial Hsp60. RESULTS: In oligoarticular JIA patients, in vitro activation of PBMCs and SFMCs with Hsp60 induced a high expression of CD30 on CD4+, activated (HLA-DR-positive), memory (CD45RO+) T cells. The expression of CD30 induced by human Hsp60 was much higher than that induced by mycobacterial Hsp60. In oligoarticular JIA patients with active disease, the expression of CD30 in response to human Hsp60 was paralleled by a high interleukin-10 (IL-10):interferon-gamma (IFNgamma) ratio. In addition, restimulated human Hsp60-specific T cell lines from oligoarticular JIA patients showed a high production of IL-10 and a low production of IFNgamma. In contrast, PBMCs and SFMCs from polyarticular JIA patients responded to human Hsp60 with virtually no expression of CD30 and a low IL-10:IFNgamma ratio. CONCLUSION: The results show that T cells responding to human Hsp60 in oligoarticular JIA patients express CD30, and during active phases of the disease, these T cells have a cytokine profile with a high IL-10:IFNgamma ratio. These findings suggest that in oligoarticular JIA patients, human Hsp60-specific CD4+ cells have a regulatory function and contribute to disease remission.

Arthritis, Juvenile↗
PubMed2003

Nonlethal transfusion associated graft-versus-host disease in a severe combined immunodeficient patient.

An X-linked severe combined immunodeficient (SCID) patient received a nonirradiated erythrocyte transfusion and developed transfusion-associated graft-versus-host disease (TAGVHD), which was controllable with high-dose corticosteroids. Haplo-identical SCT was performed, after a myeloablative conditioning regimen. At day +26, he developed GVHD. Chimerism studies revealed DNA of the erythrocyte transfusion donor (ETD) and recipient only. Because of early nonengraftment and the presence of alloreactive T cells of ETD origin, the patient was treated with an immunosuppressive conditioning regimen followed by a second SCT from the same donor. While tapering immunosuppression, he again developed mild GVHD, and DNA of ETD and bone marrow donor origin were both present. On cyclosporin, the ETD-DNA signal finally disappeared. High-resolution HLA typing revealed haplo-identity between BMD, ETD and the patient, which might have contributed to the relative mild course of the TAGVHD.

Adrenal Cortex Hormones↗
PubMed2003

After chemotherapy, functional humoral response capacity is restored before complete restoration of lymphoid compartments.

Chemotherapy has, besides the beneficial effects, several adverse effects. Suppression of the immune system is one of the most important problems. Infections caused by encapsulated bacteria like Streptococcus pneumoniae are responsible for a major part of infectious problems during and after treatment. The splenic marginal zone is essential in the initiation of an immune response to encapsulated bacteria. In this study, we analysed the effects of three different cytostatic agents on humoral immune responses. We found a reduced, but detectable immune response capacity at two days after treatment although the marginal zone B cell population is severely reduced at this time point. Twenty-four days after cessation of treatment, the immune response capacity was largely restored although lymphoid compartments were still not completely restored at that time point. Apparently, the presence of only few marginal zone B cells is sufficient to evoke a rise in antibody titres and although antibody titre increases are low, even small rises are most likely clinically relevant.

Animals↗
PubMed2003

Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation.

OBJECTIVES: Familial haemophagocytic lymphohistiocytosis (FHL) is a disorder characterized by deficient cytotoxic T-cell function and activated macrophages, owing to a defect in the perforin gene and absent perforin expression. Because symptoms of patients with systemic juvenile idiopathic arthritis (sJIA) are sometimes clinically very similar to those with FHL, we studied whether perforin expression in sJIA patients would be reduced also. METHODS: We determined the perforin expression levels on two subsets of CD8(+) cells (CD8(+)CD28(-)CD45RA(-) and CD8(+)CD28(-)CD45RA(+)) and natural killer (NK) cells from patients with sJIA under conventional treatment as well as before and after autologous stem-cell transplantation (ASCT). RESULTS: CD45RA(-) cytotoxic effector cells of sJIA patients (n=13) express significantly lower levels of perforin than polyarticular juvenile idiopathic arthritis (pJIA, n=9) patients [sJIA mean fluorescence intensity (MFI) 34.6; pJIA MFI 98.0] or control donors (MFI 124.6, n=5). A similar pattern was seen in the CD45RA(+) subset. Also NK cells from sJIA patients expressed significantly less intracellular perforin (sJIA MFI 398.4; controls MFI 972.4). In four patients with sJIA who were treated with ASCT, a clear increase in perforin expression was found at 12 months after ASCT in both cytotoxic effector cell subsets (CD45RA(-) subset before ASCT MFI 13.2; 12 months after ASCT MFI 172.3). CONCLUSION: We conclude that perforin expression can be severely reduced in sJIA. This finding may implicate defective cytotoxicity and haemophagocytosis and could thus explain why sJIA may be complicated by macrophage activation syndrome. ASCT leads to a reconstitution of the (T cell) immune system with a normal expression of perforin.

Adolescent↗
PubMed2002

Therapeutic improvement of Eustachian tube function: a review.

An impaired Eustachian tube is assumed to be an important factor in the pathogenesis of different middle ear diseases. Therefore, several investigators have studied different treatment strategies to improve Eustachian tube function. The aim of this review is to provide a comprehensive summary of the results of these studies on improvement of tubal function. The English language literature was searched systematically to identify all articles that described the effect of different interventions on Eustachian tube function. Although the results were not uniform throughout the different studies and despite several restrictions of the reviewed studies, the results of this review indicate that the function may be improved by medical intervention. However, it seems premature to recommend any of the interventions reviewed in this paper to improve function in humans. More studies, preferably randomized, placebo-controlled trials, should be conducted to assess the efficacy of different interventions.

Adenoidectomy↗
PubMed2001

Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants.

Infant vaccination with conjugated Haemophilus influenzae type b (Hib) vaccine is highly effective in protecting against invasive Hib infections, but vaccine failures do occur. Twenty-one vaccine failures are reported since the introduction of the Hib conjugate vaccine in The Netherlands. Of the 14 evaluable patients, 6 children showed no antibody response to Hib polysaccharide in convalescent-phase serum (immunoglobulin [Ig] G anti-Hib level <1.0 microg/mL), including 1 child with hypogammaglobulinemia and 1 child with IgG2 deficiency. After revaccination, almost all children developed anti-Hib antibodies. In case of Hib vaccine failure, case investigation should be performed, including measurement of serum Ig concentrations as well as specific anti-Hib antibodies. Invasive Hib disease after infant conjugate Hib vaccination may be the presentation of an underlying immunodeficiency, but more often, only a decreased antibody response to Hib is found; revaccination with conjugated Hib vaccine is advised.

Adolescent↗
PubMed2001

Antibody responses to pneumococcal and haemophilus vaccinations in patients with B-cell chronic lymphocytic leukaemia.

Although vaccination against Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae type b (Hib) is recommended for immunocompromised patients, such as patients with B-cell chronic lymphocytic leukaemia (B-CLL), its protective effect is questionable. We studied antibody responses to pneumococcal polysaccharide vaccine (Pneumovax-23) and to conjugated H. influenzae type b-vaccine (Act-Hib) in 25 patients with B-CLL. After vaccination, the number of patients with antibody levels in the protective range against pneumococcal serotypes and H. influenzae b increased from 9 (38%) to 12 (50%) of 24 patients and from 8 (35%) to 11 (48%) of 23 patients, respectively. The patients with adequate antibody response to Pneumovax-23 and Act-Hib had significantly less advanced stages of B-CLL, higher gammaglobulin levels, total IgG-levels and IgG-subclasses 2 and 4 levels, and lower levels of soluble CD23. Consequently, vaccination with these vaccines should be given as soon as the diagnosis of B-CLL is made, early in the course of the disease with determination of post-vaccination antibody levels.

Aged↗