Gender Differences of B Cell Signature in Healthy Subjects Underlie Disparities in Incidence and Course of SLE Related to Estrogen

Abstract

The aim of the present study was to investigate mechanism of the gender differences of B cells. The results showed that 358 differential gene expressions (DEGs) were displayed between healthy females and males. Compared with male, 226 and 132 genes were found to be up- and downregulated in the female. 116 genes displayed possible correlation with estrogen. Moreover, the upregulated DEGs (Cav1, CD200R1, TNFRSF17, and CXCR3) and downregulated DEGs (EIF1AY and DDX3Y) in healthy female may be involved in gender predominance of some immune diseases. Furthermore, signaling pathway analysis for estrogen-relevant DEGs showed that only 26 genes were downregulated in SLE female versus SLE male, of which expressions of 8 genes had significant difference between SLE females and SLE males but are having nonsignificant difference between healthy females and healthy males. Except for the 5 Y-chromosome-related genes or varients, only 3 DEGs (LTF, CAMP, and DEFA4) were selected and qRT-PCR confirmed that the expressions of LTF and CAMP decreased significantly in B cells from female SLE patients. These data indicated that the gender differences were existent in global gene expression of B cells and the difference may be related to estrogen.

17β-estradiol contributes to the accumulation of myeloid-derived suppressor cells in blood by promoting TNF-α secretion

“…Interestingly, our and others' studies have shown that cells of males and females display several different features and behaviors [3][4][5]. For example, women had higher levels of CD4 + and CD8 + T cell activation and inflammation-associated gene expression [5]. Lymphocyte subset enumeration revealed higher B cells in females [6].…”

“…Clinical and experimental researches have demonstrated naturally occurring gender differences in immune responses [1,2]. Interestingly, our and others' studies have shown that cells of males and females display several different features and behaviors [3][4][5]. For example, women had higher levels of CD4 + and CD8 + T cell activation and inflammation-associated gene expression [5].…”

Sexual-dimorphism in human immune system aging

“…For example, a study conducted in a small cohort of young individuals showed that women have more B cells (both percentage and absolute cell counts) in their blood compared to men 8 . In addition, hundreds of genes are differentially expressed between young men and young women in sorted B cells 9 . A recent study more comprehensively described sex-biased transcripts in purified immune cells (n=1,800), the majority of which were autosomal genes 10 .…”

miRNA and mRNA expression analysis reveals potential sex-biased miRNA expression

“…performed a systematic molecular-level analysis (mainly including mRNA, DNA methylation, microRNA (miRNA) and protein expression levels), and suggested to develop sex-specific therapeutic strategies in certain cancer types1. Recent studies suggest that proteomes may differ between males and females23, and sex differences may exist in mRNA4, miRNA expression567 and isomiR (miRNA variants) expression levels89. For example, AT2R can influence vascular responses with sexually dimorphic10, and some genes are influenced by androgens or estrogen1112.…”