-
[show abstract]
[hide abstract]
ABSTRACT: Physical activity is important for muscle and bone strength in the growing child and may be impaired in paediatric patients with inflammatory bowel disease (IBD) even during quiescent disease. The SenseWearPro(2) armband allows to measure physical activity under everyday life conditions.
Thirty-nine IBD patients (27 Crohn's disease, 12 ulcerative colitis, 24 boys) in remission (n=26) or with only mild disease activity (n=13) were compared to 39 healthy age and sex-matched controls. Body weight, height, body mass index (BMI), lean body mass as phase angle α (determined by bioelectrical impedance analysis), and dynamometric grip force were expressed as age- and sex-related Z-scores. SenseWearPro(2) armbands were applied for three consecutive days to record number of steps, duration of physical activity and sleeping time. Quality of life was assessed with the German KINDL and IMPACT III questionnaires, energy intake with prospective food protocols. Differences between patients and pair-matched controls were analysed by paired t-test.
Patients showed lower Z-scores for phase angle α (difference -0.72; 95% CI [-1.10; -0.34]) and lower grip strength (-1.02 [-1.58; -0.47]) than controls. They tended towards lesser number of steps per day (-1339 [-2760; 83]) and shorter duration of physical activity (-0.44 h [-0.94; 0.06]), particularly in females and patients with mild disease. Quality of life and energy intake did not differ between patients and controls.
In spite of quiescent disease lean body mass and physical activity were reduced. Interventions to encourage physical activity may be beneficial in this lifelong disease.
Journal of Crohn s and Colitis 01/2012; 6(6):665-73. · 2.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The muscle-bone unit is crucial for normal bone development. As muscle mass is frequently reduced in pediatric patients with inflammatory bowel disease (pIBD), we investigated the impact of muscles on the bone development over time.
Bone and muscle parameters were measured repeatedly in 102 pIBD patients (67 boys; 82 Crohn's disease; 30 newly diagnosed) by peripheral quantitative computed tomography (pQCT) at the forearm. The first and last measurements were included in the evaluation. Results were expressed as sex- and age-specific and partly height-corrected Z-scores for a healthy reference population.
At baseline, patients showed reduced Z-scores for height (median -0.7; range -3.7 to 1.6), trabecular bone mineral density (TrbBMD; -0.6; 3.0-2.8), and for height-corrected cortical cross-sectional area (CSA(height); -0.4; -3.0 to 2.2), cortical thickness (CrtTh(height); -0.7; -3.0 to 1.2), and MuscleCSA(height) (-1.0; -4.9 to 2.0; all P<0.01). Cortical bone mineral density (CrtBMD) and height-corrected TotalCSA(height) Z-scores were elevated (0.57; -4.55 to 2.8, both P<0.01). Over time, TotalCSA(height) (+0.36; -1.5 to 4.5) further increased, CorticalCSA(height) (+0.21; -2.1 to 3.0) and MuscleCSA(height) (+0.64; -2.0 to 3.9, all P<0.01) improved, whereas CrtBMD decreased toward normalization (-0.36; -5.1 to 3.6, P<0.05). The change in MuscleCSA(height) significantly correlated with the changes in TrbBMD (r=0.42), TotalCSA(height) (r=0.35), CorticalCSA(height) (r=0.38), and CrtTh(height) (r=0.24; all P<0.02). The relations became even stronger after adjustment for several confounders.
Bone metabolism and geometry are altered in pIBD patients expressed by low trabecular mineral density, low cortical thickness, and high cortical mineral density. The increased height-corrected cortical CSA might reflect a compensatory effect. In our cohort, treatment increased height-corrected muscle CSA and its changes were closely associated with bone parameters. Therefore, physical activity to enhance muscle mass and bone health should be promoted in pIBD patients.
The American Journal of Gastroenterology 01/2011; 106(5):988-98. · 7.28 Impact Factor
-
Sebastian Schroepf,
Roland Kappler,
Stephan Brand, Christine Prell,
Peter Lohse,
Jürgen Glas,
Eva Hoster,
Johanna Helmbrecht,
Antje Ballauff,
Michael Berger,
Dietrich von Schweinitz,
Sibylle Koletzko,
Martin Lacher
[show abstract]
[hide abstract]
ABSTRACT: Inflammatory bowel disease (IBD) is a polygenetic disorder. Our group previously showed that a variant within the CXCL9 gene is associated with pediatric Crohn's disease. As CXCL9, CXCL10, and CXCL11 are the 3 ligands to the receptor CXCR3, the aim of this study was to investigate the colonic transcriptional activity of the CXCR3 axis and to perform SNP genotyping of a CXCL11 polymorphism in a large pediatric and adult IBD cohort.
mRNA expression of CXCR3, CXCL9, CXCL10, CXCL11, and IL8 was analyzed in colonic biopsies using real-time PCR. CXCL11 rs6817952 nucleotide substitution was determined in 501 German individuals with IBD (336 CD, 165 UC) including 258 children and 243 adults as well as in 231 controls by a TaqMan SNP genotyping assay.
CXCR3 axis genes were significantly overexpressed in inflamed colonic tissue of pediatric CD and UC patients. The prevalence of hetero- and homozygous variants of the rs6817952 genotype was higher in pediatric but not in adult CD patients compared with that in controls (P = 0.04). Moreover, carriers of the hetero- and homozygous genotype variants of rs6817952 were at increased risk for UC in all age groups (P = 0.009).
Our study provides evidence of the significant overexpression of the CXCR3 axis in active IBD, suggesting it has a role in IBD pathogenesis. The rs6817952 A variant is a risk allele for pediatric CD and UC in all age groups. Therapeutic studies will have to show whether the blockade of chemokine receptors such as CXCR3 can modulate intestinal inflammation in a clinical application.
Inflammatory Bowel Diseases 11/2010; 16(11):1882-90. · 4.86 Impact Factor
-
Folke Freudenberg,
Uwe Wintergerst,
Angela Roesen-Wolff,
Michael H Albert, Christine Prell,
Brigitte Strahm,
Sibylle Koletzko,
Stephan Ehl,
Dirk Roos,
Alberto Tommasini,
Alessandro Ventura,
Bernd H Belohradsky,
Reinhard Seger,
Joachim Roesler,
Tayfun Güngör
The Journal of allergy and clinical immunology 04/2010; 125(4):943-946.e1. · 9.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cough is a frequent symptom in children, but the differentiation of asthmatic cough from cough of other origins can be difficult. Chemokines recruit T lymphocytes to inflamed tissues, and the corresponding chemokine receptors are differentially expressed on T H 1 and T H 2 cells.
We sought to determine whether levels of T H 1/T H 2-related chemokines and their receptors differ in bronchoalveolar lavage fluid (BALF) from 12 children with allergic asthma, 15 nonatopic children with chronic cough, and 10 children without airway disease.
The T H 1-related (IFN-gamma-inducible protein of 10 kd [IP-10], IFN-gamma-inducible T cell alpha chemoattractant [ITAC], monokine induced by IFN-gamma [Mig], and IFN-gamma) and T H 2-related (thymus- and activation-regulated chemokine [TARC], macrophage-derived chemokine [MDC], IL-5, and IL-4) chemokines and cytokines were quantified in BALF by ELISA and a particle-based multiplex array. Percentages of pulmonary lymphocytes expressing CXCR3 + and CCR5 + (T H 1) and CCR4 + and CCR3 + (T H 2) chemokine receptors were determined in BALF by flow cytometry.
Pulmonary CCR4 + CD4 + cells and levels of TARC and MDC were significantly increased in asthmatic children versus children with chronic cough or without airway disease. In asthmatic children CCR4 + CD4 + cells correlated positively with levels of TARC, MDC, and serum IgE levels and negatively with FEV 1 . In contrast, CXCR3 + CD8 + cells and levels of ITAC were significantly increased in children with non-atopic chronic cough compared with the other groups. In children with chronic cough, CXCR3 + CD8 + cells correlated with levels of ITAC and IFN-gamma.
Pulmonary CCR4 + CD4 + and CXCR3 + CD8 + cells and their ligands TARC, MDC, and ITAC clearly differentiate asthmatic children from nonatopic children with chronic cough. The analysis of these markers could facilitate the diagnostic discrimination of asthma versus other reasons for chronic cough in children.
Journal of Allergy and Clinical Immunology 05/2005; 115(4):728-36. · 11.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity.
Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry.
CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children.
The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.
Respiratory research 02/2005; 6:93. · 3.36 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Th2 cells play a central role in type I allergies. However, the source of interleukin-4 which may lead to a Th1/Th2 imbalance is unknown. Valpha24+CD161+ Natural killer T (NKT) cells secrete high amounts of interleukin-4 and/or interferon-gamma and are assumed to participate in the initiation of Th1/Th2 immune responses. Their contribution to the development of Th2-dependent type I allergies is controversial. Our objective in this paper was to determine whether Valpha24+CD161+ NKT cells differ in atopic and non-atopic adults. Venous blood was obtained from thirteen atopic and sixteen healthy adult probands. Valpha24+CD161+ NKT cells were determined in CD4+, CD8(bright/dim) and CD4-CD8- lymphocytes by flow cytometry. At the molecular level, the amounts of T cell receptor (TCR) AV24-AJ18 transcripts were quantified with respect to TCRAV24 chain transcripts alone or to all TCR alpha chain transcripts. To detect potential inserted nucleotides in the N-region, a novel real-time PCR-based technology was applied. Both CD4+ and CD4-CD8- NKT cells were present at higher frequencies than CD8+ NKT cells in all probands. CD8(dim) NKT cell levels were lower in healthy individuals, although not statistically significantly different to the patients. Amounts of AV24-AJ18 transcripts in relation to total TCR alpha-chains and to TCRAV24 alone were equal in both proband groups. N-region diversity was detected in four clones from four different individuals, but altered the amino acid sequence in only one clone of an atopic donor. Analysis of Valpha24+CD161+ NKT cell frequencies at both the cellular and molecular levels failed to reveal significant differences in peripheral blood of atopic and non-atopic probands. If NKT cells contribute to development of type I allergies they must do so at earlier times or in other locations.
Immunobiology 02/2003; 208(4):367-80. · 3.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Th2 cells play a central role in type I allergies. However, the source of interleukin-4 which may lead to a Th1/Th2 imbalance is unknown. Vα24+CD161+ Natural killer T (NKT) cells secrete high amounts of interleukin-4 and/or interferon-γ and are assumed to participate in the initiation of Th1/Th2 immune responses. Their contribution to the development of Th2-dependent type I allergies is controversial.
Our objective in this paper was to determine whether Vα24+CD161+ NKT cells differ in atopic and non-atopic adults.
Venous blood was obtained from thirteen atopic and sixteen healthy adult probands. Vα24+CD161+ NKT cells were determined in CD4+, CD8bright/dim and CD4−CD8− lymphocytes by flow cytometry. At the molecular level, the amounts of T cell receptor (TCR) AV24-AJ18 transcripts were quantified with respect to TCRAV24 chain transcripts alone or to all TCR alpha chain transcripts. To detect potential inserted nucleotides in the N-region, a novel real-time PCR-based technology was applied.
Both CD4+ and CD4−CD8− NKT cells were present at higher frequencies than CD8+ NKT cells in all probands. CD8dim NKT cell levels were lower in healthy individuals, although not statistically significantly different to the patients. Amounts of AV24-AJ18 transcripts in relation to total TCR alpha-chains and to TCRAV24 alone were equal in both proband groups. N-region diversity was detected in four clones from four different individuals, but altered the amino acid sequence in only one clone of an atopic donor.
Analysis of Vα24+CD161+ NKT cell frequencies at both the cellular and molecular levels failed to reveal significant differences in peripheral blood of atopic and non-atopic probands. If NKT cells contribute to development of type I allergies they must do so at earlier times or in other locations.
Immunobiology.
-
Susanne Krauss-Etschmann,
Dominik Hartl,
Joachim Heinrich,
Agim Thaqi, Christine Prell,
Christina Campoy,
Francesco S Molina,
Andreas Hector,
Tamas Decsi,
Dolores J Schendel,
Berthold V Koletzko
[show abstract]
[hide abstract]
ABSTRACT: The microbial environment in early infancy or even in utero may modulate the risk to develop allergic disease. Since Toll-like receptors (TLR) recognize microbial products, we hypothesized that maternal allergies may be associated with decreased levels of TLR2, TLR4 and CD14 mRNA in mothers and their offspring. 185 healthy pregnant women from Germany (n = 48), Hungary (n = 50) and Spain (n = 87) were enrolled in a European multicenter study. Levels of TLR2, TLR4 and CD14 mRNA were quantified in maternal peripheral blood samples taken at delivery and placental cord blood samples. Numbers of TLR2+, TLR4+ and CD14+ monocytes were quantified by flow cytometry in 42 cord blood samples obtained from the German participants. Bivariate and multivariate regression analyses were performed. Maternal allergies were associated with significantly lower levels of TLR2/4/CD14 mRNA in maternal blood and cord blood samples. Maternal and fetal TLR2/4/CD14 mRNA levels were significantly correlated with each other (TLR2 r = 0.42; TLR4 r = 0.58; CD14 r = 0.54). The results suggest that maternal allergy status may affect allergic risk in offspring through a decreased expression of fetal TLR2/4/CD14.
Clinical Immunology 118(2-3):292-9. · 4.05 Impact Factor
