title: Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma.
abstract: Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital.|Center for Inflammatory Diseases, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Hamsten
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Häggmark
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital.
authors.forename: J
authors.initials: J
authors.lastname: Grundström
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Mikus
authors.affiliation: SciLifeLab, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Lindskog
authors.affiliation: Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.|Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J R
authors.initials: JR
authors.lastname: Konradsen
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Eklund
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Pershagen
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.|Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Wickman
authors.affiliation: Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Grunewald
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.|Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Melén
authors.affiliation: Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.|Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Hedlin
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital.
authors.forename: M
authors.initials: M
authors.lastname: van Hage
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007535:Isomerases / Q000097:blood* / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D043562:Receptors, G-Protein-Coupled / Q000097:blood* / Q000378:metabolism; D012129:Respiratory Function Tests
chemical_list: D015415:Biomarkers; D018946:Chemokine CCL5; C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; D007535:Isomerases
keywords: asthma; biomarker; childhood; plasma; protein