Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering
BackgroundThe advent of biologics has significantly transformed treatment strategies for neuromyelitis optica spectrum disorder (NMOSD). However, there are no biomarkers that predict relapses associated with steroid tapering; therefore, it is critical to identify potential indicators of disease acti...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1508977/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832557385253650432 |
|---|---|
| author | Ryohei Yamamura Makoto Kinoshita Yoshiaki Yasumizu Yoshiaki Yasumizu Yoshiaki Yasumizu Tomohiro Yata Keigo Kihara Daisuke Motooka Daisuke Motooka Naoyuki Shiraishi Yasuko Sugiyama Shohei Beppu Hisashi Murata Naoshi Koizumi Itsuki Sano Toru Koda Tatsusada Okuno Hideki Mochizuki |
| author_facet | Ryohei Yamamura Makoto Kinoshita Yoshiaki Yasumizu Yoshiaki Yasumizu Yoshiaki Yasumizu Tomohiro Yata Keigo Kihara Daisuke Motooka Daisuke Motooka Naoyuki Shiraishi Yasuko Sugiyama Shohei Beppu Hisashi Murata Naoshi Koizumi Itsuki Sano Toru Koda Tatsusada Okuno Hideki Mochizuki |
| author_sort | Ryohei Yamamura |
| collection | DOAJ |
| description | BackgroundThe advent of biologics has significantly transformed treatment strategies for neuromyelitis optica spectrum disorder (NMOSD). However, there are no biomarkers that predict relapses associated with steroid tapering; therefore, it is critical to identify potential indicators of disease activity. In this study, we collected peripheral blood mononuclear cells (PBMCs) from NMOSD patients during steroid tapering and performed bulk RNA sequencing to analyze changes in immune dynamics caused by steroid reduction.MethodsPBMCs were collected at 3–5 timepoints from 10 NMOSD patients at our hospital (including one relapse case), and bulk RNA sequencing was performed. All patients were positive for anti-AQP4 antibodies and had no history of biologic use.ResultsIn one relapsed patient, gene groups with decreased expression at relapse were observed predominantly in monocytes, with upregulation in anti-inflammatory pathways such as IL-10, while the upregulated genes were related to interferon signaling. Moreover, after steroid tapering, in non-relapsed patients, genes with increased expression were enriched in inflammatory pathways, represented by interferon signaling, while genes with decreased expression were enriched in pathways related to IL-10 and glucocorticoid receptors. Weighted gene co-expression network analysis identified modules that correlated with steroid dosage, and the modules inversely correlated with steroid dosage were enriched in monocytes, with marked immune signature of interferon pathway.ConclusionThis study identified peripheral blood transcriptome signatures that could lead to the identification of clinically relevant NMOSD disease activity biomarkers, and further highlights the pivotal role of interferon and IL-10 signaling in NMOSD. |
| format | Article |
| id | doaj-art-803ea35ac7db413a807e06fc13f0613b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-803ea35ac7db413a807e06fc13f0613b2025-02-03T05:11:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15089771508977Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid taperingRyohei Yamamura0Makoto Kinoshita1Yoshiaki Yasumizu2Yoshiaki Yasumizu3Yoshiaki Yasumizu4Tomohiro Yata5Keigo Kihara6Daisuke Motooka7Daisuke Motooka8Naoyuki Shiraishi9Yasuko Sugiyama10Shohei Beppu11Hisashi Murata12Naoshi Koizumi13Itsuki Sano14Toru Koda15Tatsusada Okuno16Hideki Mochizuki17Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, JapanIntegrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanIntegrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, JapanGenome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanBackgroundThe advent of biologics has significantly transformed treatment strategies for neuromyelitis optica spectrum disorder (NMOSD). However, there are no biomarkers that predict relapses associated with steroid tapering; therefore, it is critical to identify potential indicators of disease activity. In this study, we collected peripheral blood mononuclear cells (PBMCs) from NMOSD patients during steroid tapering and performed bulk RNA sequencing to analyze changes in immune dynamics caused by steroid reduction.MethodsPBMCs were collected at 3–5 timepoints from 10 NMOSD patients at our hospital (including one relapse case), and bulk RNA sequencing was performed. All patients were positive for anti-AQP4 antibodies and had no history of biologic use.ResultsIn one relapsed patient, gene groups with decreased expression at relapse were observed predominantly in monocytes, with upregulation in anti-inflammatory pathways such as IL-10, while the upregulated genes were related to interferon signaling. Moreover, after steroid tapering, in non-relapsed patients, genes with increased expression were enriched in inflammatory pathways, represented by interferon signaling, while genes with decreased expression were enriched in pathways related to IL-10 and glucocorticoid receptors. Weighted gene co-expression network analysis identified modules that correlated with steroid dosage, and the modules inversely correlated with steroid dosage were enriched in monocytes, with marked immune signature of interferon pathway.ConclusionThis study identified peripheral blood transcriptome signatures that could lead to the identification of clinically relevant NMOSD disease activity biomarkers, and further highlights the pivotal role of interferon and IL-10 signaling in NMOSD.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1508977/fullNMOSDsteroidtranscriptome signatureIL-10interferon |
| spellingShingle | Ryohei Yamamura Makoto Kinoshita Yoshiaki Yasumizu Yoshiaki Yasumizu Yoshiaki Yasumizu Tomohiro Yata Keigo Kihara Daisuke Motooka Daisuke Motooka Naoyuki Shiraishi Yasuko Sugiyama Shohei Beppu Hisashi Murata Naoshi Koizumi Itsuki Sano Toru Koda Tatsusada Okuno Hideki Mochizuki Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering Frontiers in Immunology NMOSD steroid transcriptome signature IL-10 interferon |
| title | Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering |
| title_full | Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering |
| title_fullStr | Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering |
| title_full_unstemmed | Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering |
| title_short | Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering |
| title_sort | transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering |
| topic | NMOSD steroid transcriptome signature IL-10 interferon |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1508977/full |
| work_keys_str_mv | AT ryoheiyamamura transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT makotokinoshita transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT yoshiakiyasumizu transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT yoshiakiyasumizu transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT yoshiakiyasumizu transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT tomohiroyata transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT keigokihara transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT daisukemotooka transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT daisukemotooka transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT naoyukishiraishi transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT yasukosugiyama transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT shoheibeppu transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT hisashimurata transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT naoshikoizumi transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT itsukisano transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT torukoda transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT tatsusadaokuno transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering AT hidekimochizuki transcriptomesignatureinthebloodofneuromyelitisopticaspectrumdisorderundersteroidtapering |