ESPE Abstracts

Background: Cis-gender females are known to mount stronger immune responses to invading pathogens or vaccines than cis-gender males. However, this is also associated with increased risk of autoimmunity. 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 or vaccine responses; switched isotypes play a significant role in autoimmunity pathogenesis. T-follicular helper cells (Tfh) provide vital assistance to B-cells in CSR. This study sought to investigate the impact of a person’s chromosomal complement and hormonal milieu on B-cell CSR. In testing samples from healthy cis- and trans-gendered individuals, an in vivo, age-adjusted model of these effects was created.

Methods: Peripheral blood samples were collected with informed consent from cis-gender male (n = 35) and female (n = 53) post-pubertal volunteers (14-28 years), and trans-gender male (on testosterone and/or GnRH-analogue; n = 25) and female (on oestradiol and/or GnRHa; n = 19) volunteers (16-19 years). 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 and number of groups (unpaired t-test/Mann-Whitney U, one-way ANOVA/Kruskal-Wallis).

Results: Cis-females had greater percentages of class-switched B-cells than cis-males. In trans-males, just treatment with GnRHa was sufficient to also significantly decrease the levels of class-switched B-cells, and the addition of testosterone treatment saw no further decrease. Treatment with GnRHa with or without oestradiol in trans-females, however, was not associated with the increase seen in cis-females. Indeed, trans-females had the lowest percentage of class-switched B-cells of all groups. These patterns were replicated when B-cells were stained specifically for IgG/A/M/D. 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 those on GnRHa versus gender-affirming-hormones.

Conclusions: Sex hormones may differentially affect the humoral immune responses of those assigned female at birth versus 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.