Erika Bongen
Graduate Student
BMIR, Stanford University

Thursday, April 13, 2017, 12:00pm to 1:00 pm
MSOB Conference Room X-275

ABSTRACT:
Sex and gender biases in the incidence of autoimmunity and infectious disease imply that women have stronger immune responses. Women are at higher risk of autoimmune diseases, while men are more likely to die of infectious disease. Molecular factors driving this phenomenon may be detectable in the transcriptome, as it reflects immune activation, hormonal regulation, and chromosome status. We performed an immunologically focused investigation of robust transcriptional sex differences across global populations. First, we performed an integrated multi-cohort analysis of 6 cohorts consisting of 458 individuals to identify a 178-gene signature, called the Immune Sex Expression Signature (iSEXS), which is differentially expressed between healthy male and female human adults in the blood across populations. We validated iSEXS in 3 additional cohorts of 128 samples. Second, we examined sex differences in immune cell frequencies to determine whether iSEXS was driven by cell frequencies or phenotype. Using deconvolution, a method of predicting cell frequencies from bulk gene expression, we performed a meta-analysis of sex differences in cell frequencies across populations. We validated our results in an independent mass cytometry dataset and found that males had higher levels of monocytes. Third, we examined the role of sex hormones and chromosomes in the regulation of iSEXS. We observed that 25% of iSEXS is located on the sex chromosomes. Importantly, in a cohort of disorders of sexual development, XY-individuals with normal female genitalia expressed the iSEXS at similar levels as XY-males, indicating that the iSEXS is primarily driven by chromosomal differences. As a robust gene signature across populations, iSEXS has applications in understanding why women and men have differential risks of autoimmunity and infection.