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Biomedical subjects

Xavier Bossuyt

Publications and source records attributed to Xavier Bossuyt.

At least 19 recordsLinked to original sources
PubMed2007

Contribution of genetic and environmental factors in the pathogenesis of Crohn's disease in a large family with multiple cases.

BACKGROUND: A large family of Moroccan immigrants was investigated. In this family the father developed Crohn's disease (CD) after moving from Morocco to Belgium and successively 4 of his 8 children subsequently developed CD. There was no previous history of familial CD. METHODS: The family was interviewed at their home and an elaborated questionnaire was completed. The food and sanitation characteristics of the family were investigated. Moreover, serological markers were tested in all family members, including ASCA, ASCAg, ALCA, ACCA, Omp, and ANCA, using enzyme-linked immunosorbent assay and indirect immunofluorescence. Genetic variants in CARD15, TLR4, NOD1, CARD8, and DLG5 associated with CD were tested as well. The complete medical history of all patients was reviewed. RESULTS: There were no known genetic variants associated with CD in this family. None of the serological antibodies could discriminate between patients and unaffected family members, although the antibody titers were higher in diseased family members as compared with the healthy family members. CONCLUSION: The occurrence of 5 new cases of CD within 1 Moroccan family after immigration to Belgium cannot be explained by the known genetic susceptibility factors, and thus suggests a major environmental factor probably not related to sanitation in childhood.

Adolescent↗
PubMed2006

Toll-like receptor 2 and Toll-like receptor 4 polymorphisms in invasive pneumococcal disease.

BACKGROUND: Toll-like receptors (TLRs) recognize distinct pathogen-associated molecular patterns and trigger anti-microbial host defense responses. Several in vitro and in vivo studies in mice indicate that TLR2 and TLR4 are involved in the defense against Streptococcus pneumoniae. Studies have revealed associations between polymorphisms in TLRs and human diseases. The effect of polymorphisms in TLR2 and TLR4 in the human defense to S. pneumoniae has not been studied. METHODS: We genotyped 99 Caucasian patients with invasive pneumococcal disease and 178 Caucasian controls for the known R579H, P631H and R753Q polymorphisms in TLR2 and the D299G polymorphism in TLR4 with PCR-RFLP methods. RESULTS: The distribution of the TLR2 R579H, P631H and R753Q and TLR4 D299G variants was not significantly different between the patients and the controls. After stratification of the patient population by age, sex, diagnosis, and mortality no significant differences for the TLR2 R753Q genotype and TLR4 D299G genotype were found between various patient subgroups and between patient subgroups and the control population. It should be mentioned that for the TLR2 polymorphisms neither the control group nor the patient group contains homozygous mutant individuals. CONCLUSION: We found no association between TLR2 and TLR4 polymorphisms and invasive pneumococcal infection.

Adolescent↗
PubMed2006

Coexistence of (partial) immune defects and risk of recurrent respiratory infections.

BACKGROUND: Respiratory infections are major causes of morbidity and mortality, but determinants of susceptibility are poorly defined. We studied whether and to what extent immunologic and genetic factors are associated with increased susceptibility to respiratory infections. METHODS: We evaluated the prevalence of IgA, IgM, IgG, and IgG subclass deficiencies, impairment in the antibody response against pneumococcal polysaccharides, G2m(n) allotypes, Fc gamma RIIa polymorphisms, partial C2 and partial C4 deficiency, promoter polymorphisms in MBL2, and lymphocyte subset deficiencies in a control population and in consecutive children with recurrent respiratory infections. RESULTS: IgA and/or IgG subclass deficiency was found in 27 of 55 patients (49%) and 6 of 43 controls (14%) (P = 0.0006). An impaired antibody response to polysaccharides was found in 7 patients (19%) and in 0 of 37 controls (P = 0.002). The Gm(n)marker was absent in 25 of 55 patients (45%) and 6 of 42 controls (14%) (P = 0.009). The MBL2 variants O/O, A/O, and A/A occurred in 9, 14, and 32 of the 55 patients, respectively, and in 1, 19, and 23 of the 43 controls, respectively (P = 0.05). There was no increase in the prevalence of partial C4 deficiency, C2 deficiency, lymphocyte subset deficiency, or Fc gamma RIIa polymorphism in the patients compared to the controls. A combination of at least 2 immune defects was found in 31 of 55 patients (56%) and in 4 of 42 controls (11.6%) (P <0.0001). CONCLUSION: Specific antipolysaccharide antibody deficiency, IgA and/or IgG subclass deficiency, Gm(n) allotype, and MBL2 genotype are susceptibility factors for recurrent respiratory infections, and coexistence of several immune defects is the strongest risk factor in this study.

Adolescent↗
PubMed2006

IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease.

BACKGROUND: About 2% of childhood episodes of invasive pneumococcal disease (IPD) are recurrent, and most remain unexplained. OBJECTIVE: To report two cases of otherwise healthy, unrelated children with recurrent IPD as the only clinical infectious manifestation of an inherited disorder in nuclear factor-kappaB(NF-kappaB)-dependent immunity. RESULTS: One child carried two germline mutations in IRAK4, and had impaired cellular responses to interleukin (IL)1 receptor and toll-like receptor (TLR) stimulation. The other child carried a hemizygous mutation in NEMO, associated with a broader impairment of NF-kappaB activation, with an impaired cellular response to IL-1R, TLR and tumour necrosis factor receptor stimulation. The two patients shared a narrow clinical phenotype, associated with two related but different genotypes. CONCLUSIONS: Otherwise healthy children with recurrent IPD should be explored for underlying primary immunodeficiencies affecting the IRAK4-dependent and NEMO-dependent signalling pathways.

Anti-Bacterial Agents↗
PubMed2006

Quantification of IgG antibodies to Aspergillus fumigatus and pigeon antigens by ImmunoCAP technology: an alternative to the precipitation technique?

BACKGROUND: We evaluated the ImmunoCAP technique for measurement of IgG specific to Aspergillus fumigatus and pigeon antigens. METHODS: We used ImmunoCAP and precipitation technique to measure concentrations of IgG to A. fumigatus or pigeon antigens in sera from 265 patients and 42 controls. We also evaluated linearity, interference, imprecision, concordance, and diagnostic accuracy of the measuring techniques. RESULTS: The precipitation and ImmunoCAP technique showed moderate concordance (kappa, 0.46 for both A. fumigatus and pigeon antibodies). Specific IgG results for A. fumigatus and pigeon were linear (r = 0.98 and 0.97, respectively), with interrun reproducibility rates of 23% and 14% and maximal interference of 36.5% and 8% by lipid and 24% and 21% by hemolysis, respectively. A. fumigatus antibody concentrations were higher in patients with aspergillosis and allergic bronchopulmonary aspergillosis (ABPA) (median, 103 and 70.1 mgA/L, respectively) than in patients with other pulmonary diseases (median, 18.15-33.40 mgA/L). Antibodies to pigeon antigens were high in patients with hypersensitivity pneumonitis (median, 1024 mgA/L) but also in patients with other pulmonary diseases (median, 445 mgA/L). Antibody titers were substantially higher in patients with other pulmonary diseases and contact with pigeons (median, 1060 mgA/L) than in patients without antigen contact (median, 27.35 mgA/L) (P <0.004). CONCLUSIONS: Agreement between the precipitation and ImmunoCAP technique was 86% for A. fumigatus and 70% for pigeon antigens. Highest concentrations of specific IgG to A. fumigatus were found in patients with aspergillosis and ABPA. Our results suggest that antigen contact was the most important variable affecting the presence of antibodies to pigeon antigen.

Adolescent↗
PubMed2006

Towards zero prevalence of chronic Pseudomonas aeruginosa infection in children with cystic fibrosis.

BACKGROUND: Data from the Belgian Cystic Fibrosis Registry consistently show that in one of the seven reference centres, the prevalence of Pseudomonas aeruginosa is half that observed at the national level. OBJECTIVES: To report the characteristics of non-transplanted patients in this clinic at the end of 2003, with special focus on paediatric patients. To describe and discuss our policy of inhaled antibiotic therapy. FINDINGS: The prevalence of P. aeruginosa among 116 patients is 20.7%. The chronic colonization rate is 19.8% but only 2.8% in patients aged under 18 (n=72). Serologic data strongly support these results. Most paediatric patients (95%) are prescribed inhaled antibiotics, at least on an intermittent basis but the mean number of days of intravenous antibiotic treatment is four times lower than in other CF children in Belgium. 70% of children have an FEV1> or =90% predicted. DISCUSSION: We have reported a distinctly low rate of chronic colonization by P. aeruginosa in a cohort of CF children and suspect that a strategy of early, often < > use of inhaled antibiotics, progressively implemented for over 15 years has substantially contributed to these results. Given the major impact of chronic P. aeruginosa colonization on prognosis in CF, it is suggested that a large prospective study of this approach is warranted.

Administration, Inhalation↗
PubMed2006

Successful allogeneic hemopoietic stem cell transplantation in a child who had anhidrotic ectodermal dysplasia with immunodeficiency.

Anhidrotic ectodermal dysplasia with immunodeficiency is associated with multiple infections and a poor clinical outcome. Hypomorphic mutations in nuclear factor kappaB essential modulator (NEMO)/IkappaB kinase complex and a hypermorphic mutation in inhibitor alpha of nuclear factor kappaB (IkappaBalpha) both result in impaired nuclear factor kappaB activation and are associated with X-recessive and autosomal-dominant forms of anhidrotic ectodermal dysplasia with immunodeficiency, respectively. Autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency is also associated with a severe T-cell phenotype. It is not known whether hematopoietic stem cell transplantation can cure immune deficiency in children with anhidrotic ectodermal dysplasia with immunodeficiency. A boy with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency and a severe T-cell immunodeficiency underwent transplantation at 1 year of age with haploidentical T-cell-depleted bone marrow after myeloablative conditioning. Engraftment occurred, with full hematopoietic chimerism. Seven years after transplantation, clinical outcome is favorable, with normal T-cell development. As expected, the developmental features of the anhidrotic ectodermal dysplasia syndrome have appeared and persisted. This is the first report of successful hematopoietic stem cell transplantation in a child with anhidrotic ectodermal dysplasia with immunodeficiency. Hematopoietic stem cell transplantation is well tolerated and efficiently cures the profound immunodeficiency associated with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency.

Chimerism↗
PubMed2006

Mannose-binding lectin genotype and invasive pneumococcal infection.

Invasive pneumococcal disease is a serious infection that primarily affects young children and elderly or immunocompromised persons, but it also can affect healthy persons. Mannose-binding lectin (MBL) is a mediator of innate host immunity that activates the complement pathway and directly opsonizes pathogens. Variant structural codon and promoter MBL alleles have been associated with susceptibility to infections. Sixty-three Belgian patients with invasive pneumococcal disease and 162 healthy Belgian controls were genotyped for MBL alleles. We found a nonsignificant increased risk between the MBL structural codon variants (52, 54, and 57) and invasive pneumococcal disease. Combining our data with similar data from Kronberg et al. (J Infect Dis 2002;185:1517-20) indicated that MBL structural variants contributed to a small but significant increased risk of invasive pneumococcal disease. On the other hand, the -221 and -550 promoter allele distribution and the prevalence of the combined MBL structural and promoter -221 variant alleles were not significantly different between the patient group and the control group.

Adolescent↗
PubMed2006

CD4+ T lymphocytes expressing CD40 ligand help the IgM antibody response to soluble pneumococcal polysaccharides via an intermediate cell type.

Streptococcus pneumoniae causes serious infections in children, the elderly, and immunocompromised patients. Protection against infections with S. pneumoniae is mediated through Abs against the capsular polysaccharides (caps-PS). We previously showed that the murine Ab response to caps-PS is dependent on CD40-CD40L interaction. In the present paper, we addressed the question of whether the CD40-CD40L-mediated modulation of the anti-caps-PS immune reaction is the result of a direct interaction between B lymphocytes and T lymphocytes or of an indirect interaction. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice did not mount anti-caps-PS Abs. SCID/SCID mice reconstituted with B lymphocytes from wild-type mice and CD4+ T lymphocytes from wild-type mice but not CD4+ T lymphocytes from CD40L knockout mice stimulated the anti-caps-PS Ab response. This indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in a CD40L-dependent manner. SCID/SCID mice reconstituted with B lymphocytes from CD40 knockout mice and CD4+ T lymphocytes from wild-type mice generated an anti-caps-PS Ab response that could be inhibited by MR1, a blocking anti-CD40L Ab. These data indicated that CD4+ T lymphocytes stimulated the anti-caps-PS Ab response in an indirect way. Finally, lethally irradiated CD40 knockout mice reconstituted with bone marrow from wild-type mice mounted an anti-caps-PS Ab response that was comparable to the Ab response in wild-type mice, revealing that the required CD40 was on hemopoietic cells. In conclusion, we provide evidence that CD4+ T lymphocytes expressing CD40L stimulate the Ab response to soluble caps-PS by interacting with CD40-expressing non-B cells.

Animals↗
PubMed2006

Extremely elevated C-reactive protein.

BACKGROUND: C-reactive protein (CRP) is a widely used inflammatory marker. Yet, the clinical significance and outcome of extremely elevated CRP levels are poorly characterized. METHODS: We collected all patients seen at a university hospital in 2004 with at least one CRP level above 500 mg/l and retrospectively analyzed their electronic files, focusing on patient characteristics, clinical diagnosis, microbiology and vital outcome. RESULTS: CRP was above 500 mg/l in 130 patients with a median age of 62 years. Patient characteristics, settings, etiologies of inflammation, comorbidities and microbiology varied widely. Infections, mainly bacterial, accounted for 88% of episodes. Outcome was fatal in 36% of all patients and in 61% of patients with active malignancies. CONCLUSION: A wide variety of infections, especially bacterial, that are generally readily identified account for the majority of instances of extreme CRP elevation. Mortality is high, certainly in oncological patients.

Journal Article↗
PubMed2006

Advances in serum protein electrophoresis.

A major advance in serum protein electrophoresis in the last decade has been the introduction of capillary zone electrophoresis (CZE). Two dedicated automated multichannel instruments for serum protein separation by CZE in clinical laboratories are available, the Paragon CZE 2000 (Beckman Coulter, CA) and the Capillarys (Sebia, France). This chapter focuses on the performance of these commercial multichannel CZE systems. Following topics are addressed: precision, comparison of CZE with gel-based methods, dysproteinemia analysis by CZE, detection and identification of monoclonal proteins by CZE, quality control, and interferences. Examples of electrophoretic patterns are given.

Blood Proteins↗