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Article ; Online: Breathing New Life into Interstitial Lung Disease in Rheumatoid Arthritis.

Gregersen, Peter K / Gravallese, Ellen M

2018 Volume 379, Issue 23, Page(s) 2265–2266

MeSH term(s)	Arthritis, Rheumatoid ; Humans ; Lung Diseases, Interstitial ; Mucin-5B ; Respiration
Chemical Substances	MUC5B protein, human ; Mucin-5B
Language	English
Publishing date	2018-10-20
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe1811767
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Article ; Online: Genetics. A genomic road map for complex human disease.

Gregersen, Peter K

Science (New York, N.Y.)

2014 Volume 343, Issue 6175, Page(s) 1087–1088

MeSH term(s)	Crohn Disease/genetics ; Dendritic Cells/immunology ; Female ; Gene Expression Regulation/immunology ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Host-Pathogen Interactions/genetics ; Humans ; Immunity, Innate/genetics ; Interferon Regulatory Factor-7/genetics ; Male ; Monocytes/immunology ; STAT Transcription Factors/genetics
Chemical Substances	IRF7 protein, human ; Interferon Regulatory Factor-7 ; STAT Transcription Factors
Language	English
Publishing date	2014-03-07
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1251426
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Societal costs and survival of patients with biopsy-verified non-alcoholic steatohepatitis: Danish nationwide register-based study.

Rudolfsen, Jan Håkon / Gluud, Lise Lotte / Grønbæk, Henning / Jensen, Majken K / Vyberg, Mogens / Olsen, Jens / Bo Poulsen, Peter / Hovelsø, Nanna / Gregersen, Nikolaj Ture / Thomsen, Anne Bloch / Jepsen, Peter

Annals of hepatology

2024 Volume 29, Issue 3, Page(s) 101285

Abstract: Introduction and objectives: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups.: Materials and ... ...

Abstract	Introduction and objectives: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups. Materials and methods: Nationwide Danish healthcare registers were used to include all patients (≥18 years) diagnosed with biopsy-verified NAFLD (1997-2021). Patients were classified as having simple steatosis or non-alcoholic steatohepatitis (NASH) with or without cirrhosis, and all matched with liver-disease free reference groups. Healthcare costs and labour market outcomes were compared from 5 years before to 11 years after diagnosis. Patients were followed for 25 years to analyse risk of disability insurance and death. Results: 3,712 patients with biopsy-verified NASH (n = 1,030), simple steatosis (n = 1,540) or cirrhosis (n = 1,142) were identified. The average total costs in the year leading up to diagnosis was 4.1-fold higher for NASH patients than the reference group (EUR 6,318), 6.2-fold higher for cirrhosis patients and 3.1-fold higher for simple steatosis patients. In NASH, outpatient hospital contacts were responsible for 49 % of the excess costs (EUR 3,121). NASH patients had statistically significantly lower income than their reference group as early as five years before diagnosis until nine years after diagnosis, and markedly higher risk of becoming disability insurance recipients (HR: 4.37; 95 % CI: 3.17-6.02) and of death (HR: 2.42; 95 % CI: 1.80-3.25). Conclusions: NASH, simple steatosis and cirrhosis are all associated with substantial costs for the individual and the society with excess healthcare costs and poorer labour market outcomes.
MeSH term(s)	Humans ; Non-alcoholic Fatty Liver Disease/economics ; Non-alcoholic Fatty Liver Disease/mortality ; Non-alcoholic Fatty Liver Disease/epidemiology ; Denmark/epidemiology ; Female ; Male ; Registries ; Middle Aged ; Adult ; Health Care Costs ; Biopsy/economics ; Cost of Illness ; Liver Cirrhosis/economics ; Liver Cirrhosis/mortality ; Liver Cirrhosis/epidemiology ; Aged ; Insurance, Disability/economics ; Insurance, Disability/statistics & numerical data
Language	English
Publishing date	2024-01-23
Publishing country	Mexico
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2188733-0
ISSN	1665-2681
ISSN	1665-2681
DOI	10.1016/j.aohep.2024.101285
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Article: Increased plasma lipopolysaccharide-binding protein and altered inflammatory mediators in overweight women suggest a state of subclinical endotoxemia.

Metz, Christine N / Xue, Xiangying / Chatterjee, Prodyot K / Adelson, Robert P / Brines, Michael / Tracey, Kevin J / Gregersen, Peter K / Pavlov, Valentin A

Research square

2023

Abstract: Chronic low-grade inflammation has been recognized as an underlying event linking obesity to cardiovascular disease (CVD). However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we determined the ... ...

Abstract	Chronic low-grade inflammation has been recognized as an underlying event linking obesity to cardiovascular disease (CVD). However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we determined the levels of key circulating biomarkers of endotoxemia and inflammation, including lipopolysaccharide-binding protein (LBP), CRP, IL-6, leptin, and adiponectin in adult female subjects (n = 20) who were lean or overweight and had high cholesterol and/or high blood pressure - two important conventional risk factors for CVD. Plasma levels of LBP (a recognized marker of metabolic endotoxemia in obesity) were significantly higher in the overweight group compared with the lean group (P = 0.005). The levels of CRP, a general marker of inflammation, were also significantly higher in overweight subjects (P = 0.01), as were IL-6 (P = 0.02) and leptin (P = 0.002), pro-inflammatory mediators associated with cardiovascular risk. Levels of adiponectin, an adipokine with anti-inflammatory and anti-atherogenic functions, were significantly lower in the overweight group (P = 0.002). The leptin/adiponectin ratio, a preferential atherogenic marker was significantly increased in women who are overweight (P = 0.02). LBP, CRP, leptin, and adiponectin levels significantly correlated with BMI, but not with age. These results reveal the presence of subclinical endotoxemia and a pro-inflammatory state in overweight women and are of interest for further studies with the goal for improved understanding of women's cardiovascular health.
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3356683/v1
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Article ; Online: Cell type-specific eQTLs in the human immune system.

Gregersen, Peter K

Nature genetics

2012 Volume 44, Issue 5, Page(s) 478–480

Abstract: A new study reports the mapping of gene expression in primary immune cell subsets, showing the presence of cell type-specific cis and trans expression quantitative trait loci (eQTLs). The identification of cell type-specific trans-regulated networks can ... ...

Abstract	A new study reports the mapping of gene expression in primary immune cell subsets, showing the presence of cell type-specific cis and trans expression quantitative trait loci (eQTLs). The identification of cell type-specific trans-regulated networks can inform functional studies of susceptibility loci identified from genome-wide association studies for human complex diseases.
MeSH term(s)	B-Lymphocytes/metabolism ; Genetic Markers/genetics ; Genetic Predisposition to Disease ; HLA Antigens/genetics ; Humans ; Monocytes/metabolism ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics
Chemical Substances	Genetic Markers ; HLA Antigens
Language	English
Publishing date	2012-04-26
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng.2258
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

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Article ; Online: Proteomic and Single-Cell Transcriptomic Dissection of Human Plasmacytoid Dendritic Cell Response to Influenza Virus.

Ghanem, Mustafa H / Shih, Andrew J / Khalili, Houman / Werth, Emily G / Chakrabarty, Jayanta K / Brown, Lewis M / Simpfendorfer, Kim R / Gregersen, Peter K

Frontiers in immunology

2022 Volume 13, Page(s) 814627

Abstract: Plasmacytoid dendritic cells [pDCs] represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons. This function of pDCs is critical for effective antiviral defenses and has been implicated ... ...

Abstract	Plasmacytoid dendritic cells [pDCs] represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons. This function of pDCs is critical for effective antiviral defenses and has been implicated in autoimmunity. While IFN-I and select cytokines have been recognized as pDC secreted products, a comprehensive agnostic profiling of the pDC secretome in response to a physiologic stimulus has not been reported. We applied LC-MS/MS to catalogue the repertoire of proteins secreted by pDCs in the unperturbed condition and in response to challenge with influenza H1N1. We report the identification of a baseline pDC secretome, and the repertoire of virus-induced proteins including most type-I interferons, various cytokines, chemokines and granzyme B. Additionally, using single-cell RNA-seq [scRNA-seq], we perform multidimensional analyses of pDC transcriptional diversity immediately
MeSH term(s)	Chromatography, Liquid ; Cytokines/metabolism ; Dendritic Cells ; Humans ; Influenza A Virus, H1N1 Subtype/metabolism ; Interferon Type I/metabolism ; Proteomics ; Tandem Mass Spectrometry ; Transcriptome
Chemical Substances	Cytokines ; Interferon Type I
Language	English
Publishing date	2022-03-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.814627
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Article ; Online: T helper 17 axis and endometrial macrophage disruption in menstrual effluent provides potential insights into the pathogenesis of endometriosis.

Miller, Jessica E / Lingegowda, Harshavardhan / Sisnett, Danielle J / Metz, Christine N / Gregersen, Peter K / Koti, Madhuri / Tayade, Chandrakant

F&S science

2022 Volume 3, Issue 3, Page(s) 279–287

Abstract: Objective: To identify immune cells, cytokines, and immune cell transcriptome in the menstrual effluent (ME) of women with endometriosis compared with that of healthy donors.: Design: Live immune cells were isolated from human ME samples and were ... ...

Abstract	Objective: To identify immune cells, cytokines, and immune cell transcriptome in the menstrual effluent (ME) of women with endometriosis compared with that of healthy donors. Design: Live immune cells were isolated from human ME samples and were analyzed by flow cytometry to identify various immune cell populations. Selected cytokines from the same patients were evaluated using multiplex cytokine analyses. The transcriptome of the immune cell population was subsequently profiled using NanoString nCounter's PanCancer Immune panel. Setting: Academic institution. Patient(s): Surgically confirmed endometriosis patients (n = 14) and healthy fertile donors (n = 19). Intervention(s): None. Main outcome measure(s): In-depth immune cell profiling of ME obtained from women with endometriosis compared with that of healthy donors. Result(s): ME analysis revealed that the number of T helper 17 (T Conclusion(s): We demonstrate for the first time that the levels of T
MeSH term(s)	Cytokines/immunology ; Endometriosis/pathology ; Endometrium ; Female ; Humans ; Macrophages/immunology ; Th17 Cells/immunology ; Transforming Growth Factor alpha/immunology
Chemical Substances	Cytokines ; Transforming Growth Factor alpha
Language	English
Publishing date	2022-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-335X
ISSN (online)	2666-335X
DOI	10.1016/j.xfss.2022.04.007
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Article ; Online: Untargeted metabolomics reveals that multiple reproductive toxicants are present at the endometrium.

Silva, Emily L / Walker, Douglas I / Coates Fuentes, Zoe / Pinto-Pacheco, Brismar / Metz, Christine N / Gregersen, Peter K / Mahalingaiah, Shruthi

The Science of the total environment

2022 Volume 843, Page(s) 157005

Abstract: Background: Recent epidemiologic research shows many environmental chemicals exhibit endocrine disrupting effects on the female reproductive system. Few studies have examined exposure at reproductive organs. Our aim was to perform a preliminary ... ...

Abstract	Background: Recent epidemiologic research shows many environmental chemicals exhibit endocrine disrupting effects on the female reproductive system. Few studies have examined exposure at reproductive organs. Our aim was to perform a preliminary untargeted metabolomic characterization of menstrual blood, a novel biofluid, to identify environmental toxins present in the endometrium and evaluate the suitability of this sample type for exposome research. Methods: Whole blood menstrual samples were collected from four women using a menstrual cup. Samples were analyzed for small molecules that include both environmental chemicals and endogenous metabolites using untargeted liquid chromatography with high-resolution mass spectrometry (LC-HRMS). Principal component analysis (PCA) and ANOVA was used to identify differences within and between individuals' menstrual blood metabolomic profiles, and the influence of the sample processing method. To assess the presence of environmental exposures, LC-HRMS chemical profiles were matched to the ToxCast chemical database, which includes 4557 commonly used commercial chemicals. Select compounds were confirmed by comparison to reference standards. Results: PCA of metabolome profiles showed analysis of menstrual blood samples were highly reproducible, with high variability in detected metabolites between participants and low variability between analytical replicates of an individual's sample. Endogenous metabolites detected in menstrual blood samples achieved good coverage of the human blood metabolome. We found 1748 annotations for environmental chemicals, including suspected reproductive toxicants such as phenols, parabens, phthalates, and organochlorines. Storage temperature for the first 24 h did not significantly influence global metabolomic profiles. Conclusion: Our results show chemical exposures linked to reproductive toxicity and endocrine disruption are present in menstrual blood, a sampling medium for the endometrium.
MeSH term(s)	Chromatography, Liquid/methods ; Endometrium ; Female ; Hazardous Substances ; Humans ; Mass Spectrometry/methods ; Metabolome ; Metabolomics/methods
Chemical Substances	Hazardous Substances
Language	English
Publishing date	2022-06-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2022.157005
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Article: A Genomic Road Map for Complex Human Disease

Gregersen, Peter K

Science. 2014 Mar. 7, v. 343, no. 6175

2014

Abstract: Despite the successes of genome-wide association studies (GWAS) in identifying genetic connections with human disease, it has become clear that interpreting these data requires a clear understanding of how these new risk genes are regulated. On pages ... ...

Abstract	Despite the successes of genome-wide association studies (GWAS) in identifying genetic connections with human disease, it has become clear that interpreting these data requires a clear understanding of how these new risk genes are regulated. On pages 1118 and 1119 of this issue, Fairfax et al. (1) and Lee et al. (2), respectively, elucidate networks of genetic regulation in the context of the human innate immune system and show how this information can be directly applied to understanding the genetics of autoimmune disorders.
Keywords	genes ; genetics ; genome-wide association study ; human diseases ; humans ; innate immunity ; risk
Language	English
Dates of publication	2014-0307
Size	p. 1087-1088.
Publishing place	American Association for the Advancement of Science
Document type	Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1251426
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Article: Increased plasma lipopolysaccharide-binding protein and altered inflammatory mediators in overweight women suggest a state of subclinical endotoxemia.

Metz, Christine N / Xue, Xiangying / Chatterjee, Prodyot K / Adelson, Robert P / Roth, Jesse / Brines, Michael / Tracey, Kevin J / Gregersen, Peter K / Pavlov, Valentin A

bioRxiv : the preprint server for biology

2023

Abstract	Chronic low-grade inflammation has been recognized as an underlying event linking obesity to cardiovascular disease (CVD). However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we determined the levels of key circulating biomarkers of endotoxemia and inflammation, including lipopolysaccharide-binding protein (LBP), CRP, IL-6, leptin, and adiponectin in adult female subjects (n=40) who were lean or overweight and had high cholesterol and/or high blood pressure - two important conventional risk factors for CVD. Plasma levels of LBP were significantly higher in the overweight group compared with the lean group (P=0.005). The levels of CRP were also significantly higher in overweight subjects (P=0.01), as were IL-6 (P=0.02) and leptin (P=0.002), pro-inflammatory mediators associated with cardiovascular risk. Levels of adiponectin, an adipokine with anti-inflammatory and anti-atherogenic functions, were significantly lower in the overweight group (P=0.002). The leptin/adiponectin ratio, a preferential atherogenic marker was significantly increased in women who are overweight (P=0.02). LBP, CRP, leptin, and adiponectin levels significantly correlated with BMI, but not with age and there was a significant correlation between LBP and IL-6 levels. These results reveal the presence of subclinical endotoxemia and a pro-inflammatory state in overweight women and are of interest for further studies with the goal for improved understanding of cardiovascular health risks in women.
Language	English
Publishing date	2023-11-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.18.540879
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