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Biomedical subjects

Xavier Bossuyt

Publications and source records attributed to Xavier Bossuyt.

At least 37 records · Page 2Linked to original sources
PubMed2005

Serologic markers in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an enduring disease involving mostly young people, with symptoms of bloody diarrhea and abdominal cramps. Several antibodies have been associated with IBD, the 2 most comprehensively studied being autoantibodies to neutrophils (atypical perinuclear anti-neutrophil cytoplasmic antibodies) and anti-Saccharomyces cerevisiae antibodies. This review focuses on the value of these antibodies for diagnosing IBD, differentiating Crohn disease from ulcerative colitis, indeterminate colitis, monitoring disease, defining clinical phenotypes, predicting response to therapy, and as subclinical markers. Pancreatic antibodies and newly identified anti-microbial antibodies (anti-outer membrane porin C, anti-I2, and anti-flagellin) are also reviewed.

Antibodies, Bacterial↗
PubMed2005

Fcgamma-receptor IIA genotype and invasive pneumococcal infection.

Streptococcus pneumoniae is a major cause of pneumonia, bacteraemia, meningitis, and acute otitis media, especially in young children, immunocompromised patients, and elderly. Fcgamma-IIA receptor plays a crucial role in the phagocytosis of IgG2-opsonized bacteria since it is the sole receptor able to interact with IgG2 antibodies. Fcgamma-RIIA exhibits allelic polymorphisms with different capacities for binding IgG2 and phagocytosis. In a prospective study, we genotyped Fcgamma-RIIA in 55 Caucasian patients suffering from invasive pneumococcal disease and in 100 Caucasian controls. In contrast to previous reports, we found no association between Fcgamma-RIIA genotype and invasive pneumococcal disease.

Adolescent↗
PubMed2005

Blockade of CTLA-4 (CD152) enhances the murine antibody response to pneumococcal capsular polysaccharides.

The capsular polysaccharides (caps-PS) of Streptococcus pneumoniae are classified as thymus-independent antigens. Nevertheless, T lymphocytes can modulate the antibody response to caps-PS. In this study, we show that anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) treatment, along with administration of caps-PS to BALB/c mice, resulted in a dose-dependent generation of a strong caps-PS-specific antibody response. Anti-CTLA-4 treatment had no effect on the immunoglobulin G (IgG) antibody production in athymic nu/nu mice. Anti-CTLA-4 treatment stimulated the IgG antibody production in severe combined immunodeficiency (SCID)/SCID mice reconstituted with CTLA-4(-/-) B lymphocytes and wild-type T lymphocytes. This excluded the possibility that anti-CTLA-4 enhanced antibody production by direct interaction with B lymphocytes. Anti-CTLA-4 treatment enhanced the antibody production in SCID/SCID mice reconstituted with B lymphocytes and CD4(+) and CD8(+) T lymphocytes but not in SCID/SCID mice reconstituted with B lymphocytes in the absence of CD4(+) and/or CD8(+) cells. Administration of anti-CTLA-4 in BALB/c mice but not in nu/nu mice resulted in a markedly increased production of interleukin (IL)-2, IL-4, and interferon-gamma. Taken together, these data strongly suggest a role of T lymphocytes and CTLA-4 in the regulation of the antibody response to caps-PS.

Adoptive Transfer↗
PubMed2005

NEMO mutations in 2 unrelated boys with severe infections and conical teeth.

X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency is a developmental and immunologic disorder caused by mutations in nuclear factor-kappaB essential modulator (NEMO), which is essential for nuclear factor-kappaB activation. Early in life, affected boys present a typical appearance, with hypotrichosis or atrichosis, hypohidrosis or anhidrosis, and hypodontia or anodontia with conical incisors. They are also susceptible to various microorganisms, mostly pyogenic bacteria and mycobacteria. Here we report 2 unrelated boys, aged 6 and 11 years, who have novel mutations in NEMO and present conical incisors and hypodontia as their sole and long-unrecognized developmental anomaly. One child had isolated recurrent pneumococcal disease, whereas the other had multiple infections. Our observations indicate that conical incisors should prompt the search for NEMO mutations in boys with unusual infectious diseases.

Anodontia↗
PubMed2005

1alpha,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12.

1alpha,25-Dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] is a steroid hormone that regulates calcium metabolism. Besides, 1alpha,25(OH)(2)D(3 )also has pronounced immunomodulatory effects: it strongly inhibits dendritic cell (DC) maturation and impairs IL-12 production. We studied the effect of 1alpha,25(OH)(2)D(3 )on the antibody response to pneumococcal capsular polysaccharide (caps-PS) serotype 3. 1alpha,25(OH)(2)D(3) inhibited the IgG2a antibody response to caps-PS serotype 3. Besides, 1alpha,25(OH)(2)D(3) also inhibited IL-12 production and maturation of DC. Anti-IL-12 and exogenous IL-12, respectively, inhibited and stimulated the IgG2a antibody response to caps-PS serotype 3. Exogenous IL-12 abrogated the effect of 1alpha,25(OH)(2)D(3) on the IgG2a antibody response to caps-PS serotype 3, indicating that the effect of 1alpha,25(OH)(2)D(3) on the IgG2a antibody response to caps-PS serotype 3 was mediated through IL-12. In conclusion, we demonstrate that 1alpha,25(OH)(2)D(3) has an inhibitory effect on the IgG2a antibody response to caps-PS serotype 3, and that this effect was mediated trough IL-12.

Animals↗
PubMed2004

Detection of anti-SSA antibodies by indirect immunofluorescence.

BACKGROUND: HEp-2 cells that overexpress the human 60-kDa SSA antigen have been used to improve sensitivity and specificity for the detection of anti-SSA antibodies by indirect immunofluorescence. We describe a survey on the detection of anti-SSA antibodies using a commercial substrate that overexpresses SSA. METHODS: The evaluation was done on 18 371 consecutive samples submitted to the laboratory for detection of anti-nuclear antibodies, from which 188 anti-SSA antibody-containing and clinically documented samples were obtained. The presence of anti-SSA antibodies produced a distinct bright speckled pattern with nucleolar staining in 10-20% of interphase cells. The identity of all anti-SSA antibodies was confirmed by dot-blot analysis. RESULTS: Samples containing anti-SSA antibodies were separated into three main groups: group I, distinctive SSA pattern and other nuclear staining (50%); group II, only the distinctive SSA pattern (29%); group III, nuclear staining but without the distinctive SSA pattern (21%). Anti-SSA antibodies with concurrent SSB antibodies were associated with group I, whereas anti-SSA antibodies with concurrent U(1)-RNP antibodies were associated with group III. Group I included mainly patients with Sjogren syndrome and systemic lupus erythematosus (SLE), whereas group III included patients with mixed connective tissue disease and SLE. Diseases not classically associated with the presence of anti-SSA antibodies were found in group II in >50% of the cases. CONCLUSIONS: SSA-positive individuals were identified in a population selected on the basis of HEp-2000 positivity. Our study highlights diseases associated with anti-SSA antibodies and associations between the presence of the distinctive SSA pattern on HEp-2000 and some clinical conditions.

Antibodies, Antinuclear↗
PubMed2004

Diagnostic accuracy of ten second-generation (human) tissue transglutaminase antibody assays in celiac disease.

BACKGROUND: Anti-tissue transglutaminase (tTG) assays that use human tTG as antigen have recently become available. We evaluated commercially available assays with human tTG antigen to estimate their diagnostic accuracies and to determine whether they agree sufficiently to be used interchangeably. METHODS: Ten commercially available second-generation anti-tTG assays were evaluated. The following populations were studied: celiac disease (CD) patients at the time of diagnosis without (n = 70) or with (n = 5) IgA deficiency; diseased controls (n = 70); and CD patients without (n = 28) or with (n = 2) IgA deficiency during follow-up. All individuals included in the study underwent intestinal biopsy. Technical performance (linearity, interference, precision, correlation, and agreement) and diagnostic accuracy (sensitivity and specificity) were compared. Anti-gliadin and anti-endomysium antibodies were also measured. RESULTS: IgA anti-tTG results correlated well overall, but numerical values differed. Diagnostic sensitivity ranged between 91% and 97% and specificity between 96% and 100%. These were higher than the sensitivity and specificity of the IgA endomysium assay and the IgA gliadin assay. Generally, IgG anti-tTG was less sensitive but more specific than IgG anti-gliadin for the diagnosis of CD in the small group of IgA-deficient patients. CONCLUSIONS: Overall diagnostic performance of IgA tTG assays is acceptable and comparable among the different assays, but numerical values differ. Standardization is needed.

Adolescent↗
PubMed2004

Partial loss of presenilins causes seborrheic keratosis and autoimmune disease in mice.

Presenilin (PS1) and (PS2) are the centers of gamma-secretase that release Abeta from APP in Alzheimer's disease (AD). They cleave signaling proteins like Notch and downregulate beta-catenin to modulate Wnt signaling. Inactivation of PS1 or PS1 and PS2 causes a prenatally lethal 'Notch phenotype,' which has hampered investigation of PS function in adulthood seriously. We have thus turned towards PS1+/-PS2-/- mice which carry the most severe reduction of PS alleles compatible with survival, to analyze the consequences of impaired PS function especially in adulthood. In these 'partial deficient' mice, PS1 protein concentration is considerably lowered, functionally reflected by reduced gamma-secretase activity and impaired beta-catenin downregulation. Their phenotype is normal up to approximately 6 months, when the majority of the mice develop an autoimmune disease characterized by dermatitis, glomerulonephritis, keratitis and vasculitis, as seen in human systemic lupus erythematosus. Besides B-cell dominated infiltrates, we observe a hypergammaglobulinemia with immune complex deposits in several tissues, high-titer nuclear autoantibodies and an increased CD4+/CD8+ ratio. The mice further develop a benign skin hyperplasia similar to human seborrheic keratosis as opposed to malignant keratocarcinomata observed in skin-specific PS1 'full' knockouts. A partial reduction of PS function in PS1+/-PS2-/- mice causes a novel phenotype in adulthood unrelated to the developmental defects of full knockouts. As PS1+/-PS2+/- mice remain healthy, this points towards a sharply defined minimum of PS function. Skin and immune system appear to be especially sensitive targets of impaired PS function and may need careful monitoring if gamma-secretase inhibitors are envisaged for treating AD.

Alzheimer Disease↗
PubMed2004

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40-CD40 ligand interaction.

Protection against infections with Streptococcus pneumoniae is mediated by antibodies against the capsular polysaccharides (caps-PS). Here we show that in in vitro experiments CD4+ T lymphocytes stimulate and CD8+ T lymphocytes inhibit the human anti-caps-PS antibody response. Using antagonistic anti-CD40 and antagonistic anti-CD40 ligand (CD40L) monoclonal antibodies, we showed that the CD4+ T lymphocyte-mediated stimulation is dependent on the CD40-CD40L interaction. The role of CD40L was further illustrated by the observation that CD4+ T lymphocytes obtained from a patient with hyper-IgM syndrome were unable to enhance the immune response to caps-PS. Furthermore, CD4+ T lymphocytes from cord blood, which did not express CD40L in response to stimulation with caps-PS, failed to stimulate the antibody response of adult B lymphocytes to caps-PS. These in vitro findings were confirmed by in vivo experiments in which SCID/SCID mice were reconstituted with human mononuclear cells. Furthermore, we showed that caps-PS induce production of IL-4, IL-6, IL-10, and IFN-gamma, and that this enhanced production was inhibited by blocking the CD40-CD40L interaction. This is the first demonstration that the human immune response to caps-PS, which is markedly regulated by T lymphocytes, is dependent on the CD40-CD40L interaction.

Animals↗
PubMed2004

Interferences in clinical capillary zone electrophoresis of serum proteins.

Capillary zone electrophoresis (CZE) of serum proteins has become a well-accepted method for the separation of serum proteins and for the detection of monoclonal proteins in clinical laboratories. As CZE uses ultraviolet detection for direct protein quantification, exogenous ultraviolet-absorbing substances are a novel challenge, not present in conventional gel-based methods in which protein is quantified by dye binding. This minireview gives a survey of interfering substances, including iodinated contrast agents and antibiotics.

Absorption↗
PubMed2004

Conflicting results between electrophoresis methods of serum M-proteins.

The quantification of monoclonal immunoglobulins by protein electrophoresis has been helpful in determining the prognosis for the patient. In a 65-year old man with documented IgG lambda monoclonal gammopathy, a discrepancy in the detection and quantification of this M-protein was found when studied by four different electrophoretic methods. On a high-resolution agarose method with acid violet staining a prominent peak was seen in the fast gamma-region. A lower resolution agarose method using an amido black staining showed a small mid-gamma restriction, and no spike was detected by high-resolution or lower resolution capillary zone electrophoresis. The discrepancy was not attributable to a migration in the beta-region leading to masking by transferrin or C3 peak, incorrect separation on CZE due to a high isoelectric point (pI > 8.5) or pentamerization of IgM M-proteins. Therefore, other causes for discrepancies should be investigated.

Aged↗