Chromosomes, hormone changes in cis-, transgender patients drive regulatory T-cell changes
Click Here to Manage Email Alerts
Sex-chromosomes and rapid changes in sex hormones during adolescence may drive changes in regulatory T-cell frequency and function, 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 “sex hormone-associated transcriptomic profiles that overlap by gender,” which may impact the pathogenesis of juvenile-onset systemic lupus erythematosus. Specifically, they concluded that young post-pubertal cisgender men demonstrate a more anti-inflammatory regulatory T-cell profile. In addition, transgender patients receiving gender-affirming hormonal therapy demonstrated significant changes in regulatory T-cell transcriptome.
“Sex differences across the immune system, including fundamental differences in the frequency and activity of T-cell subsets, have been described by gender across ethnicities,” George A. Robinson, PhD, of University College London, and colleagues wrote. “Investigating 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 groups of patients. Groups eligible for inclusion in the analysis included healthy post-pubertal cisgender individuals aged 16 to 25 years, healthy prepubertal cisgender individuals aged 6 to 11 years, transgender individuals aged 18 to 19 years undergoing gender-affirming therapy, and post-pubertal cisgender individuals with juvenile-onset SLE aged 14 to 25 years.
Patients with SLE were eligible for inclusion in the analysis if they met the 1997 criteria from the American College of Rheumatology or the 2012 Systemic Lupus International Collaborating Clinics criteria. These patients were diagnosed before reaching 18 years of age. Additionally, for inclusion in the post-puberty cohorts, patients were required to be at stage four or five on the Tanner scale.
The researchers collected peripheral blood mononuclear cell samples from participants. These samples were evaluated for subsets of 28 immune cell types. The researchers assessed regulatory T cells’ suppressive capabilities using fluorescence-activated cell sorting. Additionally, they used RNA sequencing gene ontology pathways between 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-onset SLE group. Blood was collected between Sept. 5, 2012, and Nov. 6, 2019.
According to the researchers, there was a statistically significant elevation in the number of regulatory T cells in post-pubertal cisgender men compared with similarly aged post-pubertal cisgender women (P = .0097). Additionally, regulatory T cells from cisgender men demonstrated increased suppressive capabilities compared with samples from similarly aged cisgender women.
Meanwhile, transgender patients receiving gender-affirming hormonal therapy demonstrated significant changes in regulatory T-cell transcriptome.
Differences among regulatory T-cell frequencies were absent and suppressive capabilities were “reversed” among participants with juvenile-onset SLE.
“We have highlighted sexual dimorphisms in [regulatory T-cell (Treg-cell)] profiles and function by sex in young healthy individuals and patients with autoimmunity, showing differential influences of sex chromosomes and hormones using unique transgender cohorts,” Robinson and colleagues wrote. “This information helps us to understand the mechanistic pathogenesis of autoimmune disease and the bias towards cisgender women. Our study will help inform the future consideration of sex as a biological variable in inflammatory 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.
Collapse
Read more about
Click Here to Manage Email Alerts