Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma

Resztak, Justyna; Choe, Jane; Nirmalan, Shreya; Wei, Jian; Bruinsma, Julian; Houpt, R.; Alazizi, Adnan; Mair-Meijers, Henriette; Wen, Xiaoquan; Slatcher, Richard B.; Zilioli, Samuele; Piqué-Regi, Roger; Luca, Francesca

doi:10.1038/s41467-022-35742-z

Cited by 5 publications

(4 citation statements)

References 108 publications

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“…Cough sensitivity in children is instead influenced by airway caliber (forced expiratory volume in 1 s, FEV1) and age [37]. Recent data in children with asthma have shown that changes in gene expression differ between pre-and post-menarcheal females i.e., that there is a shift from a predominantly innate to an adaptive immunity [57]. Authors demonstrating this evidence have suggested that "gene expression changes associated with asthma and may explain sex differences in prevalence" [57].…”

Section: Other Major Differences Between Children and Adults With Res...mentioning

confidence: 99%

“…Recent data in children with asthma have shown that changes in gene expression differ between pre-and post-menarcheal females i.e., that there is a shift from a predominantly innate to an adaptive immunity [57]. Authors demonstrating this evidence have suggested that "gene expression changes associated with asthma and may explain sex differences in prevalence" [57]. It is likely but remains unknown if similar changes related to cough sensitivity are also present.…”

Section: Other Major Differences Between Children and Adults With Res...mentioning

confidence: 99%

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Cough Hypersensitivity Syndrome: Why Its Use Is Inappropriate in Children

Chang

Irwin

O’Farrell

et al. 2023

JCM

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In children and adults, chronic cough is a common symptom presenting to health professionals worldwide. It is internationally accepted that children with chronic cough should be managed with pediatric specific management guidelines. The newly proposed clinical entity of ‘cough hypersensitivity syndrome’ has gained significant attention in adult literature. Given the significant differences between childhood and adult chronic cough, including in respiratory physiology and anatomy, and cough sensitivity, we address the suitability of the use of cough hypersensitivity syndrome in children. We explore these differences between childhood and adult chronic cough, explain what cough hypersensitivity is and highlight why the term cough hypersensitivity syndrome should not be used in children.

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Section: Other Major Differences Between Children and Adults With Res...mentioning

confidence: 99%

Section: Other Major Differences Between Children and Adults With Res...mentioning

confidence: 99%

Cough Hypersensitivity Syndrome: Why Its Use Is Inappropriate in Children

Chang

Irwin

O’Farrell

et al. 2023

JCM

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“…Of the 30 gene-PBMC cell type-trait triplets with PIP > 0.5, 25 involved a trait locus that had no confidently fine-mapped gene-tissue pair (no TGFM PIP > 0.5 in GTEx-only analysis corresponding to Figures 3-6). For the 18 representative traits, TGFM identified 12 gene-PBMC cell type pairs at PIP > 0.5 for autoimmune diseases and blood cell traits (Figure 7a) vs. 5 gene-PBMC cell type pairs at PIP > 0.5 for non-blood-related traits (Figure 7b; includes 2 gene-PBMC cell type pairs for Menarche age, which we conservatively labeled as non-blood-related even though it has been reported to be partially immune-mediated 88,89 ), increasing to 23 vs. 7 for all 45 traits; this validates the importance of gene expression in blood cell types for blood-related traits.…”

Section: Tgfm Pinpoints Disease Genes and Fine-grained Cell-types In ...mentioning

confidence: 99%

Fine-mapping causal tissues and genes at disease-associated loci

Strober,

Zhang,

Amariuta

et al. 2023

Preprint

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Heritable diseases often manifest in a highly tissue-specific manner, with different disease loci mediated by genes in distinct tissues or cell types. We propose Tissue-Gene Fine-Mapping (TGFM), a fine-mapping method that infers the posterior probability (PIP) for each gene-tissue pair to mediate a disease locus by analyzing GWAS summary statistics (and in-sample LD) and leveraging eQTL data from diverse tissues to build cis-predicted expression models; TGFM also assigns PIPs to causal variants that are not mediated by gene expression in assayed genes and tissues. TGFM accounts for both co-regulation across genes and tissues and LD between SNPs (generalizing existing fine-mapping methods), and incorporates genome-wide estimates of each tissue’s contribution to disease as tissue-level priors. TGFM was well-calibrated and moderately well-powered in simulations; unlike previous methods, TGFM was able to attain correct calibration by modeling uncertainty in cis-predicted expression models. We applied TGFM to 45 UK Biobank diseases/traits (averageN= 316K) using eQTL data from 38 GTEx tissues. TGFM identified an average of 147 PIP > 0.5 causal genetic elements per disease/trait, of which 11% were gene-tissue pairs. Implicated gene-tissue pairs were concentrated in known disease-critical tissues, and causal genes were strongly enriched in disease-relevant gene sets. Causal gene-tissue pairs identified by TGFM recapitulated known biology (e.g.,TPO-thyroid for Hypothyroidism), but also included biologically plausible novel findings (e.g.,SLC20A2-artery aorta for Diastolic blood pressure). Further application of TGFM to single-cell eQTL data from 9 cell types in peripheral blood mononuclear cells (PBMC), analyzed jointly with GTEx tissues, identified 30 additional causal gene-PBMC cell type pairs at PIP > 0.5—primarily for autoimmune disease and blood cell traits, including the well-established role ofCTLA4in CD8+T cells for All autoimmune disease. In conclusion, TGFM is a robust and powerful method for fine-mapping causal tissues and genes at disease-associated loci.

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“…However, in females, changes in gene expression related to puberty demonstrate a positive correlation with asthma symptoms and an inverse correlation with pulmonary function. With a notable shift in the immune response from a predominantly innate to a more adaptive pattern in females ( Resztak et al, 2023 ).…”

Section: Adolescence Why Does Everything Change?mentioning

confidence: 99%

Winds of change a tale of: asthma and microbiome

Galeana-Cadena,

Gómez-García,

Lopez-Salinas

et al. 2023

Front. Microbiol.

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The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome’s role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus, and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches.

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Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma

Cited by 5 publications

References 108 publications

Cough Hypersensitivity Syndrome: Why Its Use Is Inappropriate in Children

Cough Hypersensitivity Syndrome: Why Its Use Is Inappropriate in Children

Fine-mapping causal tissues and genes at disease-associated loci

Winds of change a tale of: asthma and microbiome

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