title: Biomarkers associated with disease severity in allergic and nonallergic asthma.
abstract: Asthma is a complex, chronic respiratory disease with a wide clinical spectrum. Use of high-throughput technologies has generated a great deal of data that require validation. In this work the objective was to validate molecular biomarkers related to asthmatic disease types in peripheral blood samples and define their relationship with disease severity. With this purpose, ninety-four previously described genes were analyzed by qRT-PCR in 30 healthy control (HC) subjects, 30 patients with nonallergic asthma (NA), 30 with allergic asthma (AA), and 14 patients with allergy (rhinitis) but without asthma (AR). RNA was extracted from peripheral blood mononuclear cells (PBMCs) using the TRIzol method. After data normalization, principal component analysis (PCA) was performed, and multiple approaches were used to test for differential gene expression. Relevance was defined by RQ (relative quantification) and corrected P value (<0.05). Protein levels of IL-8 and MSR1 were determined by ELISA and Western blot, respectively. PCA showed 4 gene expression clusters that correlated with the 4 clinical phenotypes. Analysis of differential gene expression between clinical groups and HCs revealed 26 statistically relevant genes in NA and 69 in AA. Protein interaction analysis revealed IL-8 to be a central protein. Average levels of IL-8 were higher in the asthma patients' sera (NA: 452.28±357.72, AA: 327.46±377pg/ml) than in HCs (286.09±179.10), but without reaching statistical significance. Nine genes, especially MSR1, were strongly associated with severe NA. In conclusion, several molecular biomarkers of asthma have been defined, some of which could be useful for the diagnosis or prognosis of disease severity.
authors.affiliation: Immunology Department, IIS-Jiménez Díaz Foundation, UAM, Madrid, Spain; CIBERES, CIBER of Respiratory Diseases, Spain.
authors.forename: Selene
authors.initials: S
authors.lastname: Baos
authors.affiliation: Immunology Department, IIS-Jiménez Díaz Foundation, UAM, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Calzada
authors.affiliation: Immunology Department, IIS-Jiménez Díaz Foundation, UAM, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Cremades
authors.affiliation: CIBERES, CIBER of Respiratory Diseases, Spain; Allergy Department, Jiménez Díaz Foundation, Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Sastre
authors.affiliation: Allergy Department, Vírgen del Rocío University Hospital, Seville, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Quiralte
authors.affiliation: Allergy Department, San Cecilio University Hospital, Granada, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Florido
authors.affiliation: Immunology Department, IIS-Jiménez Díaz Foundation, UAM, Madrid, Spain; CIBERES, CIBER of Respiratory Diseases, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lahoz
authors.affiliation: Immunology Department, IIS-Jiménez Díaz Foundation, UAM, Madrid, Spain; CIBERES, CIBER of Respiratory Diseases, Spain. Electronic address: bcardaba@fjd.es.
authors.forename: Blanca
authors.initials: B
authors.lastname: Cárdaba
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D015415:Biomarkers
keywords: Allergy; Asthma; Biomarkers; Gene expression; Severity