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...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-025-00467-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jesper Just |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-631bfbb30b38443397cab4c6fc4410b2 |
| institution | Kabale University |
| issn | 2056-7944 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-631bfbb30b38443397cab4c6fc4410b22025-02-09T12:48:25ZengNature Portfolionpj Genomic Medicine2056-79442025-02-0110111410.1038/s41525-025-00467-7Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypesJesper Just0Lukas Ochsner Reynaud Ridder1Emma Bruun Johannsen2Jens Magnus Bernth Jensen3Mikkel Steen Petersen4Helene Viborg Christensen5Kenneth Kjærgaard6Jacob Redder7Simon Chang8Kirstine Stochholm9Anne Skakkebæk10Claus Højbjerg Gravholt11Department of Molecular Medicine, Aarhus University HospitalDepartment of Molecular Medicine, Aarhus University HospitalDepartment of Molecular Medicine, Aarhus University HospitalDepartment of Molecular Medicine, Aarhus University HospitalDepartment of Clinical Immunology, Aarhus University HospitalDepartment of Endocrinology, Aarhus University HospitalDepartment of Data and Data UtilizationDepartment of Data and Data UtilizationDepartment of Molecular Medicine, Aarhus University HospitalDepartment of Clinical Medicine, Aarhus UniversityDepartment of Molecular Medicine, Aarhus University HospitalDepartment of Molecular Medicine, Aarhus University HospitalAbstract 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.https://doi.org/10.1038/s41525-025-00467-7 |
| spellingShingle | 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 Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes npj Genomic Medicine |
| title | Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes |
| title_full | Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes |
| title_fullStr | Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes |
| title_full_unstemmed | Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes |
| title_short | Elevated levels of neutrophils with a pro-inflammatory profile in Turner syndrome across karyotypes |
| title_sort | elevated levels of neutrophils with a pro inflammatory profile in turner syndrome across karyotypes |
| url | https://doi.org/10.1038/s41525-025-00467-7 |
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