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

Jesper Just; Lukas Ochsner Reynaud Ridder; Emma Bruun Johannsen; Jens Magnus Bernth Jensen; Mikkel Steen Petersen; Helene Viborg Christensen; Kenneth Kjærgaard; Jacob Redder; Simon Chang; Kirstine Stochholm; Anne Skakkebæk; Claus Højbjerg Gravholt

doi:10.1038/s41525-025-00467-7

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

Jesper Just^*, Lukas Ochsner Reynaud Ridder^*, Emma Bruun Johannsen, Jens Magnus Bernth Jensen, Mikkel Steen Petersen, Helene Viborg Christensen, Kenneth Kjærgaard, Jacob Redder, Simon Chang, Kirstine Stochholm, Anne Skakkebæk, Claus Højbjerg Gravholt^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

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.

Original language	English
Article number	9
Journal	npj Genomic Medicine
Volume	10
Issue	1
ISSN	2056-7944
DOIs	https://doi.org/10.1038/s41525-025-00467-7
Publication status	Published - Dec 2025

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Just, J., Ridder, L. O. R., Johannsen, E. B., Jensen, J. M. B., Petersen, M. S., Christensen, H. V., Kjærgaard, K., Redder, J., Chang, S., Stochholm, K., Skakkebæk, A., & Gravholt, C. H. (2025). Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes. npj Genomic Medicine, 10(1), Article 9. https://doi.org/10.1038/s41525-025-00467-7

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title = "Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes",

abstract = "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.",

author = "Jesper Just and Ridder, {Lukas Ochsner Reynaud} and Johannsen, {Emma Bruun} and Jensen, {Jens Magnus Bernth} and Petersen, {Mikkel Steen} and Christensen, {Helene Viborg} and Kenneth Kj{\ae}rgaard and Jacob Redder and Simon Chang and Kirstine Stochholm and Anne Skakkeb{\ae}k and Gravholt, {Claus H{\o}jbjerg}",

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month = dec,

doi = "10.1038/s41525-025-00467-7",

language = "English",

volume = "10",

journal = "npj Genomic Medicine",

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Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes. / Just, Jesper ; Ridder, Lukas Ochsner Reynaud ; Johannsen, Emma Bruun et al.
In: npj Genomic Medicine, Vol. 10, No. 1, 9, 12.2025.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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

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.

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SN - 2056-7944

VL - 10

JO - npj Genomic Medicine

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

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