Peter C. Groot

The experience sampling method as an mHealth tool to support self-monitoring, self-insight, and personalized health care in clinical practice

The experience sampling method (ESM) builds an intensive time series of experiences and contexts in the flow of daily life, typically consisting of around 70 reports, collected at 8–10 random time points per day over a period of up to 10 days.

Cytotoxic T lymphocyte antigen 4 polymorphisms and allergic asthma

Allergic asthma is a complex disease characterized by reversible airway obstruction, elevated levels of IgE, chronic eosinophilic airway inflammation, lung tissue remodelling, and airway hyper-reactivity (AHR) to bronchospasmogenic stimuli. T helper type-2 (Th2) lymphocytes, which produce a distinctive set of cytokines, including IL4, IL5, IL9, IL10, and IL13, play a crucial role in the initiation and progression of allergic asthma. Therefore, knowledge of the activation requirements of T cells and the subsequent differentiation into Th1, Th2, or regulatory T cell subsets is important to understand the aberrant Th2-mediated inflammatory responses to allergens observed in allergic individuals, including those with asthma. Moreover, this knowledge can be used to design novel therapeutic strategies that target the Th2lymphocyte. An area of research that has continued to attract a lot of attention is the role of the CD28/CTLA4:B7-1/B7-2 co-stimulatory pathway that is crucial for the activation of naı̈ve T cells (Fig. 1). Interestingly, several studies have shown linkage of total serum IgE or other allergy phenotypes to chromosome 2q32–q33, a region encoding both CD28 and CTLA4 genes. In this issue of Clinical and Experimental Allergy, Yang et al. [1] report that a polymorphism in CTLA4 is associated in females, but not in males, to elevated serum levels of total IgE and allergic rhinitis.

Mouse genetic model for antigen-induced airway manifestations of asthma

Allergic asthma is a genetically complex disease characterized by allergen-specific immunoglobulin (Ig)E, eosinophilic inflammation of the lungs and airway hyper-responsiveness to bronchospasmogenic stimuli. In this study, we compared 13 recombinant congenic (RC) mouse strains in an ovalbumin model of allergic asthma. Different intensities and types of responses are observed throughout the RC strains. Intensities range from resistance to asthma in CcS05, to a very severe bronchoconstrictive reaction upon methacholine challenge for the parental STS strain. All strains show a ‘modified’ Th2 response except CcS14, which shows a ‘true’ Th2 response. When data from all strains are pooled, airway reactivity shows significant correlations with the serum Ig levels and the levels of interleukin (IL)-4, IL-5 and IL-13 in the broncho-alveolar lavage (BAL), at low dosage of methacholine (below 25 mg/ml), whereas at high dosage airway reactivity only correlates with BAL neutrophil levels. This indicates that at least two different mechanisms are involved in the airway reactivity to methacholine. None of these correlations can be found in every individual strain, which demonstrates that the asthma traits in this mouse model are genetically dissociated and that the loci can be genetically mapped.

Isolation of DNA markers informative in purebred dog families by genomic representational difference analysis (gRDA).

Genomic Representational Difference Analysis (gRDA) is a subtractive DNA method to clone the differences between two related genomes, called tester and driver. We have evaluated this method to obtain polymorphic DNA markers for pedigree dogs. Amplified size-selected genomic restriction fragments (amplicons) of two dog littermates were repeatedly hybridized to each other in order to remove (subtract) those restriction fragments common to both sibs. Already after two rounds of subtractive hybridization, a clear enrichment of presumably tester-specific restriction fragments was observed, which was even more pronounced after the third round of subtraction. A plasmid library of 3000 recombinant clones was constructed of the second round and of the third round difference product. DNA sequence determination of randomly chosen clones of each difference product showed that approximately 1000 unique clones were obtained in the second-round difference product and approximately 500 in the third-round difference product. About half of the clones identified in the second-round difference product were also present in the third-round difference product. Of the second-round difference product, 39 different gRDA fragments could be identified, of which 21 were tester specific. In the third-round difference product, 22 different gRDA fragments were identified, of which 18 were tester specific. There were 13 fragments in common, resulting in a total of 48 different fragments. In order to establish the localization of these markers, we performed mapping using the dog radiation hybrid panel RHDF5000. Of 39 mapped clones, 29 were mapped to 20 existing RH groups, and 10 remained unlinked. It is concluded that gRDA is suitable to generate DNA markers to track disease genes within lines of pedigree dogs.

Identification of the Mhc Region as an Asthma Susceptibility Locus in Recombinant Congenic Mice

Mouse models of allergic asthma are characterized by airway hyperreactivity (AHR), Th2-driven eosinophilic airway inflammation, high allergen-specific IgE (anti-OVA IgE) levels in serum, and airway remodeling. Because asthma susceptibility has a strong genetic component, we aimed to identify new asthma susceptibility genes in the mouse by analyzing the asthma phenotypes of the Leishmania major resistant (lmr) recombinant congenic (RC) strains. The lmr RC strains are derived from C57BL/6 and BALB/c intercrosses and carry congenic loci on chromosome 17 (lmr1) and 9 (lmr2) in both backgrounds. Whereas the lmr2 locus on chromosome 9 contributes to a small background-specific effect on anti-OVA IgE and AHR, the lmr1 locus on chromosome 17 mediates a strong effect on Th2-driven eosinophilic airway inflammation and background-specific effects on anti-OVA IgE and AHR. The lmr1 locus contains almost 600 polymorphic genes. To narrow down this number of candidate genes, we performed genome-wide transcriptional profiling on lung tissue from C.lmr1 RC mice and BALB/c control mice. We identified a small number of differentially expressed genes located within the congenic fragment, including a number of Mhc genes, polymorphic between BALB/c and C57Bl/6. The analysis of asthma phenotypes in the C.B10-H2b RC strain, carrying the C57Bl/6 haplotype of the Mhc locus in a BALB/c genetic background, reveals a strikingly similar asthma phenotype compared with C.lmr1, indicating that the differentially expressed genes located within the C.B10-H2b congenic fragment are the most likely candidate genes to contribute to the reduced asthma phenotypes associated with the C57Bl/6 allele of lmr1.