Sex hormone-dependent and independent regulation of serum BAFF and TNFα in a cohort of transgender men and women.

Abstract

The risk of inflammatory diseases is sex dependent, but it remains unknown whether this is due to impact of sex hormones or sex chromosomes. Transgender individuals represent a unique cohort for studying relative influence of endocrine and chromosomal factors. Here we compared serum levels of B-cell activating-factor (BAFF) and tumor necrosis factor α (TNFα) in transgender men (TM), transgender women (TW), cisgender women (CW) and cisgender men (CM). BAFF and TNFα were measured in the serum of 26 CW, 30 CM, 27 TM and 16 TW individuals. To determine the responsiveness of immune cells, TNFα was measured in bacterial lipopolysaccharide (LPS) treated peripheral leukocytes. BAFF was higher in CF (998 pg/mL) and TW (973 pg/mL) compared to CM (551 pg/mL) (p<0.0001), and TM (726 pg/mL) (p<0.0001). No difference in BAFF levels was shown between subjects grouped according to the number of X chromosomes. TNFα was higher in CM (174 pg/mL) than TW (2.3 pg/mL) (p=0.027) and TM (27.4 pg/mL) (p=0.028). LPS-induced TNFα was higher in CM (2524 pg/mL) and TM (2078 pg/mL) than in CW (1332 pg/mL) (both p<0.0001) and TW (1602 pg/mL) (both p=0.009). Sex hormones and sex chromosomes have different impact on cytokines involved in sex-dependent inflammatory response. Concentration of BAFF and LPS stimulated TNFα secretion depended on sex hormone levels, whereas basal TNFα was regulated by both sex hormone-dependent and -independent factors.