Chromosomes and hormonal changes in cis and transgender patients lead to regulatory changes in T cells

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November 01, 2022

2 minute read

Source/Disclosures

Disclosures:
This study was funded by Versus Arthritis, the UK National Institute for Health Research University College London Hospital Biomedical Research Centre, Lupus UK and the Rosetrees Trust. The authors report no relevant financial information.


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According to data published in The Lancet Rheumatology.

The researchers added that they found changes in regulatory T cells between cisgender men and cisgender women, and “overlapping sex hormone-associated transcriptomic profiles by gender,” which may impact the pathogenesis of juvenile-onset systemic lupus erythematosus. Specifically, they concluded that post-pubertal cisgender young men exhibit a more anti-inflammatory regulatory T cell profile. Additionally, transgender patients receiving gender-affirming hormone therapy demonstrated significant changes in the T-cell regulatory transcriptome.

hormone therapy with syringe

According to the data, sex chromosomes and rapid changes in sex hormones during adolescence can lead to changes in the frequency and function of regulatory T cells. Source: Adobe Stock

“Sex differences across the immune system, including fundamental differences in the frequency and activity of T-cell subsets, have been described by sex across ethnicities,” George A. Robinson, PhD, of University College London, and his colleagues wrote. “Studying the relationship between sex hormones and inflammation is important for understanding the cause of autoinflammatory diseases.”

To investigate the relationship between sex hormones, regulatory T cells, and inflammation, Robinson and colleagues conducted a cross-sectional study analyzing immune cell subsets in various patient groups. Groups eligible for inclusion in the analysis included healthy postpubertal cisgender people ages 16-25, healthy prepubertal cisgender people ages 6-11, transgender people ages 18-19 years undergoing gender affirmation therapy and post-pubescent cisgender people with juvenile LES aged 14 to 25 years.

Patients with SLE were eligible to be included in the analysis if they met the 1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria. These patients were diagnosed before the age of 18. In addition, to be included in the post-pubertal cohorts, patients had to be at stage four or five on the Tanner scale.
The researchers collected samples of peripheral blood mononuclear cells from the participants. These samples were evaluated for subsets of 28 immune cell types. Researchers assessed the suppressive abilities of regulatory T cells using fluorescence-activated cell sorting. Additionally, they used RNA sequencing gene ontology pathways across sexes, genders, and disease states.

The analysis included samples from 98 participants, including 39 in the post-pubertal cisgender group, 14 in the pre-pubertal cisgender group, 10 people in the transgender group, and 35 people in the juvenile SLE group. The blood was collected between September 5, 2012 and November 6, 2019.

According to the researchers, there was a statistically significant increase in the number of regulatory T cells in post-pubertal cisgender men compared to post-pubertal cisgender women of similar age (P = 0.0097). Additionally, regulatory T cells from cisgender males demonstrated enhanced suppressive abilities compared to age-matched cisgender female samples.

Meanwhile, transgender patients receiving gender-affirming hormone therapy demonstrated significant changes in the T-cell regulatory transcriptome.

Differences in regulatory T cell frequencies were absent and suppressive abilities were “reversed” in participants with juvenile SLE.

“We have highlighted sexual dimorphisms in [regulatory T-cell (Treg-cell)] profiles and function by sex in healthy young individuals and autoimmune patients, showing differential influences of sex chromosomes and hormones using single transgender cohorts,” Robinson and colleagues wrote. “This information helps us understand the mechanistic pathogenesis of autoimmune diseases and the bias towards cisgender women. Our study will help inform the future consideration of sex as a biological variable in inflammation research and clinical trials.

References:

  • Klein SL, et al. Nat Rev Immunol. 2016; doi:10.1038/nri.2016.90.
  • Uppal SS, et al. Cytometry B Clin Cytom. 2003; doi: 10.1038/nri.2016.90.

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