DC Field | Value | Language |
---|---|---|
dc.contributor.author | Koh, June-Young | ko |
dc.contributor.author | Kim, Doo Ri | ko |
dc.contributor.author | Son, Sohee | ko |
dc.contributor.author | Park, Hwanhee | ko |
dc.contributor.author | Kim Kyung-Ran | ko |
dc.contributor.author | Min, Sunwoo | ko |
dc.contributor.author | Lee, Ha Seok | ko |
dc.contributor.author | Jhun, Byung Woo | ko |
dc.contributor.author | Kang, Eun-Suk | ko |
dc.contributor.author | Jung, Inkyung | ko |
dc.contributor.author | Kang, Ji-Man | ko |
dc.contributor.author | Kim, Yae-Jean | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.date.accessioned | 2024-08-23T01:00:14Z | - |
dc.date.available | 2024-08-23T01:00:14Z | - |
dc.date.created | 2024-08-23 | - |
dc.date.created | 2024-08-23 | - |
dc.date.issued | 2024-04 | - |
dc.identifier.citation | JOURNAL OF CLINICAL IMMUNOLOGY, v.44, no.4 | - |
dc.identifier.issn | 0271-9142 | - |
dc.identifier.uri | http://hdl.handle.net/10203/322396 | - |
dc.description.abstract | Purpose Patients with STAT1 gain-of-function (GOF) mutations often exhibit autoimmune features. The JAK1/2 inhibitor ruxolitinib can be administered to alleviate autoimmune symptoms; however, it is unclear how immune cells are molecularly changed by ruxolitinib treatment. Then, we aimed to investigate the trnscriptional and epigenetic status of immune cells before and after ruxolitinib treatment in a patient with STAT1 GOF.Methods A patient with a heterozygous STAT1 GOF variant (p.Ala267Val), exhibiting autoimmune features, was treated with ruxolitinib, and peripheral blood mononuclear cells (PBMCs) were longitudinally collected. PBMCs were transcriptionally analyzed by single-cell cellular indexing of the transcriptomes and epitopes by sequencing (CITE-seq), and epigenetically analyzed by assay of transposase-accessible chromatin sequencing (ATAC-seq).Results CITE-seq analysis revealed that before treatment, the patient's PBMCs exhibited aberrantly activated inflammatory features, especially IFN-related features. In particular, monocytes showed high expression levels of a subset of IFN-stimulated genes (ISGs). Ruxolitinib treatment substantially downregulated aberrantly overexpressed ISGs, and improved autoimmune features. However, epigenetic analysis demonstrated that genetic regions of ISGs-e.g., STAT1, IRF1, MX1, and OAS1-were highly accessible even after ruxolitinib treatment. When ruxolitinib was temporarily discontinued, the patient's autoimmune features were aggravated, which is in line with sustained epigenetic abnormality.Conclusions In a patient with STAT1 GOF, ruxolitinib treatment improved autoimmune features and downregulated aberrantly overexpressed ISGs, but did not correct epigenetic abnormality of ISGs. | - |
dc.language | English | - |
dc.publisher | SPRINGER/PLENUM PUBLISHERS | - |
dc.title | Ruxolitinib Improves Immune-Dysregulation Features but not Epigenetic Abnormality in a Patient with STAT1 GOF | - |
dc.type | Article | - |
dc.identifier.wosid | 001197887300005 | - |
dc.identifier.scopusid | 2-s2.0-85190077229 | - |
dc.type.rims | ART | - |
dc.citation.volume | 44 | - |
dc.citation.issue | 4 | - |
dc.citation.publicationname | JOURNAL OF CLINICAL IMMUNOLOGY | - |
dc.identifier.doi | 10.1007/s10875-024-01687-9 | - |
dc.contributor.localauthor | Jung, Inkyung | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Kim, Doo Ri | - |
dc.contributor.nonIdAuthor | Son, Sohee | - |
dc.contributor.nonIdAuthor | Park, Hwanhee | - |
dc.contributor.nonIdAuthor | Kim Kyung-Ran | - |
dc.contributor.nonIdAuthor | Jhun, Byung Woo | - |
dc.contributor.nonIdAuthor | Kang, Eun-Suk | - |
dc.contributor.nonIdAuthor | Kang, Ji-Man | - |
dc.contributor.nonIdAuthor | Kim, Yae-Jean | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | STAT1 GOF | - |
dc.subject.keywordAuthor | JAK inhibitor | - |
dc.subject.keywordAuthor | ATAC sequencing | - |
dc.subject.keywordAuthor | Inborn errors of immunity | - |
dc.subject.keywordPlus | OF-FUNCTION MUTATIONS | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | UNDERLIE | - |
dc.subject.keywordPlus | DISEASE | - |
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