TY - JOUR
T1 - Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes
AU - Just, Jesper
AU - Ridder, Lukas Ochsner Reynaud
AU - Johannsen, Emma Bruun
AU - Jensen, Jens Magnus Bernth
AU - Petersen, Mikkel Steen
AU - Christensen, Helene Viborg
AU - Kjærgaard, Kenneth
AU - Redder, Jacob
AU - Chang, Simon
AU - Stochholm, Kirstine
AU - Skakkebæk, Anne
AU - Gravholt, Claus Højbjerg
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Turner syndrome (TS) presents with multiple karyotypes, including 45,X monosomy and variants such as isochromosomes and mosaicism, and is characterized by several co-morbidities, including metabolic conditions and autoimmunity. Here, we investigated the genomic landscapes across a range of karyotypes. We show that TS have a common autosomal methylome and transcriptome, despite distinct karyotypic variations. All TS individuals lacked the X chromosome p-arm, and XIST expression from the q-arm did not affect the autosomal transcriptome or methylome, highlighting the critical role of the missing p-arm with its pseudoautosomal region 1. Furthermore, we show increased levels of neutrophils and increased neutrophil activation. The increase in neutrophils was linked to TS clinical traits and to increased expression of the X-Y homologous gene TBL1X, suggesting a genetic basis, which may lead to neutrophil-driven inflammatory stress in TS. Identifying TS individuals with increased neutrophil activation could potentially mitigate the progression towards more severe metabolic issues.
AB - Turner syndrome (TS) presents with multiple karyotypes, including 45,X monosomy and variants such as isochromosomes and mosaicism, and is characterized by several co-morbidities, including metabolic conditions and autoimmunity. Here, we investigated the genomic landscapes across a range of karyotypes. We show that TS have a common autosomal methylome and transcriptome, despite distinct karyotypic variations. All TS individuals lacked the X chromosome p-arm, and XIST expression from the q-arm did not affect the autosomal transcriptome or methylome, highlighting the critical role of the missing p-arm with its pseudoautosomal region 1. Furthermore, we show increased levels of neutrophils and increased neutrophil activation. The increase in neutrophils was linked to TS clinical traits and to increased expression of the X-Y homologous gene TBL1X, suggesting a genetic basis, which may lead to neutrophil-driven inflammatory stress in TS. Identifying TS individuals with increased neutrophil activation could potentially mitigate the progression towards more severe metabolic issues.
UR - http://www.scopus.com/inward/record.url?scp=85218265161&partnerID=8YFLogxK
U2 - 10.1038/s41525-025-00467-7
DO - 10.1038/s41525-025-00467-7
M3 - Journal article
C2 - 39915521
AN - SCOPUS:85218265161
SN - 2056-7944
VL - 10
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 9
ER -