Sex hormone-dependent and -independent regulation of serum BAFF and TNF in cohorts of transgender and cisgender men and women

Background: The risk of inflammatory diseases is sex-dependent, but it rema ins unknown whether this is due to the impact of sex hormones or sex chromo somes. Transgender individuals represent a unique cohort for studying the relative influence of endocrine and chromosomal factors. Here we compared serum levels of B-cel l activating-factor (BAFF) and tumor necrosis factor (TNF) in transgender men (TM), transgender women (TW), cisgender women (CW) and cisgender men (CM). Methods: BAFF and TNF were measured in the serum of 26 CW, 30 CM, 27 TM and 16 TW individuals. To determine the responsiveness of immune cells, T NF was measured in bacterial lipopolysaccharide (LPS)-treated peripheral leukocytes. Results: 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 chr omosomes. TNF 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 TNF 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). Discussion: Sex hormones and sex chromosomes have different impacts on cyto kines involved in the sex-dependent inflammatory response. The concent ration of BAFF and LPS-stimulated TNF secretion depended on sex hormone levels, wh ereas basal TNF was regulated by both sex hormone-dependent and -independent factors.