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Publication Detail
B-cell class switching in trans- and cis-gendered healthy young people is differentially influenced by sex hormones
  • Publication Type:
    Conference presentation
  • Publication Sub Type:
  • Authors:
    Peckham H, Rosser EC, Radziszewska A, Robinson G, Martin L, De Gruijter N, Jury E, Butler G, Ciurtin C
  • Name of Conference:
    48th Meeting of the British Society for Paediatric Endocrinology and Diabetes
  • Conference place:
  • Conference start date:
  • Conference finish date:
  • Keywords:
    Hormones, Endocrinology, Immunology
  • Addresses:
    Hannah Peckham
    Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCLH and GOSH
    Division of Medicine
    5 University Street
    WC1E 6JF
    United Kingdom
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. 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 GnRHa-only and gender-affirming hormones. Sex hormones may differentially affect 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.
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