Endocrine Abstracts

Cis-gender females are known to mount stronger humoral immune responses than cis-gender males. Little is known about the immunophenotypes of transgender individuals on gender-affirming hormonal treatment, despite growing evidence that hormones influence the immune system.Via the process of class-switch recombination (CSR), B-cell immunoglobulin isotype ‘switches’ from early IgM/IgD classes to IgG/IgA/IgE. Whilst important in infection/vaccine responses; switched isotypes play a significant role in autoimmunity. T-follicular helper cells (Tfh) aid B-cells in CSR. This study investigates the impact of sex-chromosomal complement and hormonal milieu on B-cell CSR, using samples from healthy cis- and trans-gendered individuals to create an in vivo, age-adjusted model of these effects. Peripheral blood samples were collected with informed consent from cis-gender male (n = 35) and female (n = 53) post-pubertal volunteers (14-28y), and trans-gender male (on testosterone and/or GnRH-analogue; n = 25) and female (on oestradiol and/or GnRHa; n = 19) volunteers (16-19y). In-depth phenotyping of peripheral blood mononuclear cells was performed using multiparameter flow cytometry. GraphPad Prism was used for statistical testing appropriate to the data distribution/number of groups (unpaired t-test/Mann-Whitney U, one-way ANOVA/Kruskal-Wallis). Cis-females had greater percentages of class-switched B-cells than cis-males. In trans-males, GnRHa monotreatment was sufficient to also significantly decrease the levels of class-switched B-cells, and additional testosterone treatment saw no further decrease. GnRHa treatment, with or without oestradiol in trans-females, however, was not associated with the increase seen in cis-females. Indeed, trans-females had the lowest percentages of class-switched B-cells of all groups. Cis-females and -males had similar levels of Tfh cells. Both trans-females and trans-males however, trended toward lower levels of Tfh cells, with little distinction between GnRHa-only and gender-affirming hormones. Sex hormones may differentially affect humoral immune responses of those assigned female at birth vs those assigned male. Whilst trans-males followed the same decreased class-switching pattern as cis-males, a surprising and significant decrease was seen in trans-females, that did not mirror the immune phenotype of cis-females. These data support the need for further research into the interactions between hormones and chromosomal sex, as immunological outcomes in trans-gender people may differ from those in cis-gendered individuals.