title: Gender differences in inflammatory proteins and pathways in seasonal allergic rhinitis.
abstract: In model organisms, thousands of genes differ in expression between females and males. It is not known if differences on a similar scale are found in humans nor how this relates to disease. However, in allergic disease gender differences in the levels of both inflammatory cells and proteins have been shown. In this study, we found lower nasal fluid allergen-specific IgE in women than men with seasonal allergic rhinitis (SAR). This led to genome-wide analyses of gene expression in allergen-challenged CD4(+) cells from patients with SAR before and after treatment with cortisone. Before treatment, 975 genes differed in expression between women and men: 337 were higher in women. After treatment only 428 genes and one pathway differed in expression. The genes that differed in expression between women and men were over-represented in 10 pathways. Five of the pathways regulated chemotaxis. All five were less active in women. One of the pathways was induced by the eosinophilic chemokine CCL4. Analysis of nasal fluid CCL4 protein confirmed lower levels in women with seasonal allergic rhinitis, before and during the pollen season. By contrast, nasal fluid CCL3 levels did not differ between the genders. In summary, this study shows gender differences in specific inflammatory pathways and proteins in patients with seasonal allergic rhinitis. Further studies are warranted to examine if such differences have diagnostic and therapeutic implications in allergic diseases.
authors.affiliation: The Unit for Clinical Systems Biology, Department of Pediatrics, The Queen Silvia Children's Hospital, SE 41685 Göteborg, Sweden. Fredrik.Barrenas@vgregion.se
authors.forename: Fredrik
authors.initials: F
authors.lastname: Barrenäs
authors.forename: Bengt
authors.initials: B
authors.lastname: Andersson
authors.forename: Lars Olaf
authors.initials: LO
authors.lastname: Cardell
authors.forename: Michael
authors.initials: M
authors.lastname: Langston
authors.forename: Reza
authors.initials: R
authors.lastname: Mobini
authors.forename: Andy
authors.initials: A
authors.lastname: Perkins
authors.forename: Juhani
authors.initials: J
authors.lastname: Soini
authors.forename: Arne
authors.initials: A
authors.lastname: Ståhl
authors.forename: Mikael
authors.initials: M
authors.lastname: Benson
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000032:analysis; D054407:Chemokine CCL4 / Q000032:analysis*; D002633:Chemotaxis / Q000276:immunology; D015331:Cohort Studies; D004804:Eosinophils / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000032:analysis*; D018836:Inflammation Mediators / Q000276:immunology; D008297:Male; D017817:Nasal Lavage Fluid; D020411:Oligonucleotide Array Sequence Analysis; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000235:genetics*; D012737:Sex Factors
chemical_list: D000893:Anti-Inflammatory Agents; C515429:CCL3 protein, human; C066507:CCL4 protein, human; D015704:CD4 Antigens; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018836:Inflammation Mediators; D007073:Immunoglobulin E; D006854:Hydrocortisone