title: The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex.
abstract: BACKGROUND
  The relationships between total serum IgE levels and gene expression patterns in peripheral blood CD4+ T cells (in all subjects and within each sex specifically) are not known.
  
  
  METHODS
  Peripheral blood CD4+ T cells from 223 participants from the Childhood Asthma Management Program (CAMP) with simultaneous measurement of IgE. Total RNA was isolated, and expression profiles were generated with Illumina HumanRef8 v2 BeadChip arrays. Modeling of the relationship between genome-wide gene transcript levels and IgE levels was performed in all subjects, and stratified by sex.
  
  
  RESULTS
  Among all subjects, significant evidence for association between gene transcript abundance and IgE was identified for a single gene, the interleukin 17 receptor B (IL17RB), explaining 12% of the variance (r2) in IgE measurement (p value = 7 × 10(-7), 9 × 10(-3) after adjustment for multiple testing). Sex stratified analyses revealed that the correlation between IL17RB and IgE was restricted to males only (r2 = 0.19, p value = 8 × 10(-8); test for sex-interaction p < 0.05). Significant correlation between gene transcript abundance and IgE level was not found in females. Additionally we demonstrated substantial sex-specific differences in IgE when considering multi-gene models, and in canonical pathway analyses of IgE level.
  
  
  CONCLUSIONS
  Our results indicate that IL17RB may be the only gene expressed in CD4+ T cells whose transcript measurement is correlated with the variation in IgE level in asthmatics. These results provide further evidence sex may play a role in the genomic regulation of IgE.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ghunninghake@partners.org
authors.forename: Gary M
authors.initials: GM
authors.lastname: Hunninghake
authors.forename: Jen-hwa
authors.initials: JH
authors.lastname: Chu
authors.forename: Sunita S
authors.initials: SS
authors.lastname: Sharma
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Himes
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Rogers
authors.forename: Amy
authors.initials: A
authors.lastname: Murphy
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Raby
mesh_terms: D001249:Asthma / Q000097:blood / Q000235:genetics* / Q000276:immunology; D001985:Bronchial Provocation Tests; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D053722:Receptors, Interleukin-17 / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013147:Spirometry; D055815:Young Adult
chemical_list: D053722:Receptors, Interleukin-17; D007073:Immunoglobulin E