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- López-Isac, Elena, et al.
(författare)
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Brief Report : IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies
- 2016
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:9, s. 2338-2344
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome-wide association (meta-GWAS) strategy. Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
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| 2. |
- Lötstedt, Britta, et al.
(författare)
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The impact of gastrointestinal dysmotility on the aerodigestive microbiome of pediatric lung transplant recipients.
- 2020
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Ingår i: The Journal of Heart and Lung Transplantation. - 1053-2498 .- 1557-3117.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Delayed gastric emptying has been associated with increased graft rejection, althoughthe mechanism of this association is not known. This study aims to investigate the interrelationshipbetween delays in gastrointestinal motility and the diversity and composition of gastric, oropharyngeal,and lung microbiomes in pediatric lung transplant recipients.METHODS:We prospectively recruited 23 pediatric lung transplant recipients and 98 pediatric patientswith respiratory symptoms undergoing combined endoscopy and bronchoscopy. Gastric, oropharyn-geal, and bronchoalveolar lavage samples were collected for 16S sequencing. Gastric samples werealso analyzed for bile composition using liquid chromatography.RESULTS:Patients who underwent lung transplantation had significantly reduced alpha diversity in gas-tric and oropharyngeal sites compared with patients with respiratory symptoms. This reduction in alphadiversity was especially evident in gastric samples in patients with delayed gastric emptying defined asabnormal gastric emptying on nuclear scintigraphy or as an elevation in gastric bile concentration (p≤0.05). Whereas monocolonies were seen in the lungs of patients who underwent transplantation, thesewere not the same microbes seen in the stomach; the microbial overlap between lung and gastric sam-ples within patients was low, and data indicated high individual variation between lung transplantrecipients. Other contributors to reduced alpha diversity included antibiotics in combination with pro-ton pump inhibitors, especially in gastric and oropharyngeal samples.CONCLUSIONS:Lung transplant recipients have reduced microbial diversity in gastric fluid (GF) andoropharynx compared with patients who did not undergo lung transplantation. The decreased alphadiversity in GF may be associated with dysmotility.J Heart Lung Transplant 000;000:1−10ÓPublished by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.
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| 3. |
- Lötstedt, Britta, et al.
(författare)
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The impact of gastrointestinal dysmotility on the aerodigestive microbiome of pediatric lung transplant recipients
- 2021
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier Inc.. - 1053-2498 .- 1557-3117. ; 40:3, s. 210-219
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Delayed gastric emptying has been associated with increased graft rejection, although the mechanism of this association is not known. This study aims to investigate the interrelationship between delays in gastrointestinal motility and the diversity and composition of gastric, oropharyngeal, and lung microbiomes in pediatric lung transplant recipients. METHODS: We prospectively recruited 23 pediatric lung transplant recipients and 98 pediatric patients with respiratory symptoms undergoing combined endoscopy and bronchoscopy. Gastric, oropharyngeal, and bronchoalveolar lavage samples were collected for 16S sequencing. Gastric samples were also analyzed for bile composition using liquid chromatography. RESULTS: Patients who underwent lung transplantation had significantly reduced alpha diversity in gastric and oropharyngeal sites compared with patients with respiratory symptoms. This reduction in alpha diversity was especially evident in gastric samples in patients with delayed gastric emptying defined as abnormal gastric emptying on nuclear scintigraphy or as an elevation in gastric bile concentration (p ≤ 0.05). Whereas monocolonies were seen in the lungs of patients who underwent transplantation, these were not the same microbes seen in the stomach; the microbial overlap between lung and gastric samples within patients was low, and data indicated high individual variation between lung transplant recipients. Other contributors to reduced alpha diversity included antibiotics in combination with proton pump inhibitors, especially in gastric and oropharyngeal samples. CONCLUSIONS: Lung transplant recipients have reduced microbial diversity in gastric fluid (GF) and oropharynx compared with patients who did not undergo lung transplantation. The decreased alpha diversity in GF may be associated with dysmotility.
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