Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes.

Summary

Using methylome and transcriptome profiling across karyotypes, the study shows a shared autosomal signature in Turner syndrome driven by loss of Xp (including PAR1), independent of XIST. Neutrophils are increased and activated, linked to TBL1X expression and clinical traits, suggesting neutrophil-driven inflammatory stress as a mechanistic contributor to TS comorbidities.

Key Findings

• Common autosomal methylome and transcriptome across TS despite different karyotypes
• Universal loss of Xp (including PAR1); XIST expression from Xq did not alter autosomal omics
• Elevated neutrophil levels and activation linked to TS clinical traits
• Neutrophil increase associated with higher expression of X–Y homolog TBL1X, suggesting a genetic basis

Clinical Implications

Consider monitoring neutrophil counts/activation and inflammatory markers in Turner syndrome as part of cardiometabolic risk assessment. Findings may inform future trials targeting innate immune pathways to mitigate metabolic and autoimmune comorbidities.

Limitations

• Sample size and cohort details not specified in the abstract
• Cross-sectional design limits causal inference and clinical outcome linkage
• External validation in independent cohorts is needed

Future Directions

Validate neutrophil activation and TBL1X as biomarkers in independent TS cohorts; longitudinal studies to link inflammatory signatures with cardiometabolic outcomes; explore targeted anti-inflammatory or immunomodulatory interventions.