ESPEYB25 6. DSD and Gender Incongruence Gender Incongruence: Immune System Adaptation during Gender-Affirming Testosterone Treatment (2 abstracts)
6.15. Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes
Peckham H , Radziszewska A , Sikora J , de Gruijter NM , Restuadi R , Kartawinata M , Martin-Gutierrez L , Robinson GA , Deakin CT , Wedderburn LR , Jury EC , Butler G , Chambers ES , Rosser EC & Ciurtin C
J Exp Med. 2025 Apr7;222(4):e20241253. doi: 10.1084/jem.20241253
Brief summary: This study identified that among immune cell types in peripheral blood, sex differences were largest for CD19+CD27+IgD- class-switched memory B-cells, with higher numbers in females. This difference aroseonly after puberty and was no longer present after menopause. Transgender males on GnRH analogue treatment had lower numbers of these cells than control females, and postmenopausal women on estrogen treatment had higher numbers compared to untreated controls, further supporting an important role of estrogens in the regulation of this cell type. However, this only seemed to apply to XX females, as 20 transgender female adolescents (male sex registered at birth) treated with a GnRH analogue and estradiol had similar numbers of CD19+CD27+IgD- class-switched memory B-cells to control males.
Females have a higher risk of autoimmunity and for several autoimmune conditions this risk increases from pubertal age. The results of this study suggest that the influence of estrogen on CD19+CD27+IgD- class-switched memory B-cells may be an underlying mechanism. Estradiol treatment (mean duration 13 months, range 4.5-23) did not affect the number of these cells in transgender female adolescents, which the authors attributed to their XY chromosome complement. However, the dose or serum concentrations of estradiol were not reported. As previous studies have shown low serum estradiol concentrations in transgender adolescents treated with a standard pubertal induction protocol (1) it would be interesting to investigate if estradiol dose may also play a role.
Clinical studies have also investigated the risk of autoimmunity in transgender people. A recent register-based Danish study reported that before diagnosis, transgender females had an incidence rate ratio (IRR) of 1.35 (95%CI 1.04-1.77) for any autoimmune disease and 1.66 (95%CI 1.05-2.61) for type 1 diabetes mellitus compared to male controls, which the authors suggested may be related to minority stress. After diagnosis, the IRR for thyroid disease was 1.98 (95%CI 1.09-3.61) but no association was found between prescription of gender affirming hormones and the incidence of autoimmune disease in transgender females.
References: 1. Hannema SE, Schagen SEE, Cohen-Kettenis PT, Delemarre-van de Waal HA. Efficacy and Safety of Pubertal Induction Using 17β-Estradiol in Transgirls. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2356-2363.2. Andersen MS. Autoimmune diseases in 3812 Danish transgender persons and 38 120 cisgender controls before and after transgender care: a register-based cohort study. Eur J Endocrinol. 2025 Mar 27;192(4):408-417. PMID: 40086810.
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ESPE Yearbook of Paediatric Endocrinology
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