IL-17-producing cells in ankylosing spondylitis patients show gender-based differences in gene expression.

OBJECTIVES: Gender has been shown to impact disease expression in ankylosing spondylitis (AS) and Th17 cells play a key role in AS pathogenesis. To better understand what Th17-associated immune pathways are different between men and women, we compared the transcriptome of IL-17-enriched peripheral blood mononuclear cells (PBMCs) in male and female AS patients, with a particular focus on inflammatory cytokine genes. METHODS: PBMCs were collected from 10 female and 11 male AS patients at the Clinical Research Unit of MetroHealth Medical Center. IL-17-enriched PBMCs were isolated and stimulated with CytoStim. RNA-sequencing (RNA-seq) was performed on the samples, and the data were analysed using iPathwayGuide. Inflammatory markers and genes related to Th17 differentiation and function were identified based on previous studies. RESULTS: RNA-seq identified 12,893 genes with 2,851 genes with p-values <0.05 with distinct patterns of gene expression between male and female AS patients. TGF-ß, PGE2, and S100 proteins were significantly upregulated in males. Levels of IL-12B, a Th17 inducer, were lower in males compared to females. Additionally, receptors of IL-6, 12, 23, TGF-ß, and PGE2 were downregulated in males, except for IL-17RC, which was upregulated. Genes involved in Th17 differentiation showed differential expression between genders, with elevated expression of BATF, SOCS1, NKD2, and ARID5A in men and decreased expression of FOXO1. CONCLUSIONS: Transcriptomic analysis revealed that male AS patients exhibit distinct expression patterns of IL-17 pro-inflammatory genes, which may contribute to the phenotypic differences observed between genders in AS.

Exploring adolescent suicidal trajectories: The intersection of race/ethnicity, gender, and social connectedness.

INTRODUCTION: Understanding adolescent racial/ethnic and gender disparities in suicidal ideation and attempts longitudinally can help curb future suicidal risk. METHODS: Survey data (1994-2008) from the Longitudinal Study of Adolescent to Adult Health (Add Health study, n = 18,887) examined racial/ethnic and gender ideation and attempt disparities over four waves of data from across the United States (51% female; 51% White; Mage = 17.43 years at Wave 1). Repeated-measures latent class analyses described how ideation and attempt patterns present longitudinally and how racial/ethnic minority groups predict different classes based on each wave and age-appropriate social supports (i.e., parents, peers). RESULTS: Those most at-risk disclosed ideation and some attempt risk in early adolescence (Waves 1 and 2) and mostly identified as female. The second most prevalent group first disclosed ideation in their 20s and predominately identified as non-Hispanic White females. Peer connections were not significant for most groups except for non-Hispanic White males in Wave 3, while Black females who reported stronger school connections had decreased ideation and attempt rates in Wave 1 but not 2 (just 1 year later). A negative link between social supports and high-risk ideation and attempt classes was found among Black females, non-Hispanic Whites, and Latinos overall. CONCLUSIONS: As the United States becomes more diverse, understanding the unique ideation and attempt disparities are crucial. Tailoring interventions to include risk and protective mechanisms among intersectional communities could eradicate disparities. Longitudinal studies can illuminate how protective and risk factors can change over time and even within and among racial/ethnic and gender groups.