Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles
Abstract Background The rarity and heterogeneity of adult-onset Still’s disease (AOSD) pose significant challenges in understanding its precise pathogenic mechanisms, developing effective treatment options, and establishing therapeutic strategies. A comprehensive analysis of gene expression profiles...
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BMC
2025-07-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-025-03598-5 |
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| author | In-Woon Baek Hyoun-Ah Kim Kyung-Su Park Ki-Jo Kim |
| author_facet | In-Woon Baek Hyoun-Ah Kim Kyung-Su Park Ki-Jo Kim |
| author_sort | In-Woon Baek |
| collection | DOAJ |
| description | Abstract Background The rarity and heterogeneity of adult-onset Still’s disease (AOSD) pose significant challenges in understanding its precise pathogenic mechanisms, developing effective treatment options, and establishing therapeutic strategies. A comprehensive analysis of gene expression profiles could help to bridge the knowledge gaps in those areas. Methods A blood transcriptomic dataset comprising 31 patients with AOSD and 22 healthy controls was fetched. Cellular and molecular features were identified by analyzing differentially expressed genes (DEGs) and functional enrichment. Optimal molecular targets for neutrophil activation were identified using kernel-based diffusion scoring techniques. Results Blood molecular signatures indicate that neutrophil degranulation is the most enriched pathological process in AOSD. Neutrophil degranulation correlated significantly with the expression of Fcγ receptors, IL-1 receptors, and chemokine receptors and their signaling activities. IL-1 inhibitors and IL-6 inhibitors did not exhibit a diffusion score favorable for directly deactivating neutrophil degranulation, but agents targeting CXCR1/CXCR2, C5AR1, neutrophil elastase, SRC, and SYK demonstrated significant diffusion scores for neutrophil degranulation. In particular, CXCR1, CXCR2, and C5AR1 were the DEGs predominantly expressed in neutrophils and closely associated with neutrophil degranulation in a context-specific functional analysis. Conclusions Neutrophil activation is a key pathological module in AOSD. Therapeutic approaches aimed at neutrophils could offer a promising opportunity to regulate the inflammatory response in AOSD. |
| format | Article |
| id | doaj-art-df4db525f2be46bfa6cd5d3577790ead |
| institution | Kabale University |
| issn | 1478-6362 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj-art-df4db525f2be46bfa6cd5d3577790ead2025-08-20T03:37:38ZengBMCArthritis Research & Therapy1478-63622025-07-0127111310.1186/s13075-025-03598-5Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profilesIn-Woon Baek0Hyoun-Ah Kim1Kyung-Su Park2Ki-Jo Kim3Division of Rheumatology, Department of Internal Medicine, College of Medicine, Ewha Womans UniversityDepartment of Rheumatology, Ajou University School of MedicineDivision of Rheumatology, Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of KoreaDivision of Rheumatology, Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of KoreaAbstract Background The rarity and heterogeneity of adult-onset Still’s disease (AOSD) pose significant challenges in understanding its precise pathogenic mechanisms, developing effective treatment options, and establishing therapeutic strategies. A comprehensive analysis of gene expression profiles could help to bridge the knowledge gaps in those areas. Methods A blood transcriptomic dataset comprising 31 patients with AOSD and 22 healthy controls was fetched. Cellular and molecular features were identified by analyzing differentially expressed genes (DEGs) and functional enrichment. Optimal molecular targets for neutrophil activation were identified using kernel-based diffusion scoring techniques. Results Blood molecular signatures indicate that neutrophil degranulation is the most enriched pathological process in AOSD. Neutrophil degranulation correlated significantly with the expression of Fcγ receptors, IL-1 receptors, and chemokine receptors and their signaling activities. IL-1 inhibitors and IL-6 inhibitors did not exhibit a diffusion score favorable for directly deactivating neutrophil degranulation, but agents targeting CXCR1/CXCR2, C5AR1, neutrophil elastase, SRC, and SYK demonstrated significant diffusion scores for neutrophil degranulation. In particular, CXCR1, CXCR2, and C5AR1 were the DEGs predominantly expressed in neutrophils and closely associated with neutrophil degranulation in a context-specific functional analysis. Conclusions Neutrophil activation is a key pathological module in AOSD. Therapeutic approaches aimed at neutrophils could offer a promising opportunity to regulate the inflammatory response in AOSD.https://doi.org/10.1186/s13075-025-03598-5Adult-onset still’s diseaseNeutrophil activationInterleukin-1Chemokine receptors |
| spellingShingle | In-Woon Baek Hyoun-Ah Kim Kyung-Su Park Ki-Jo Kim Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles Arthritis Research & Therapy Adult-onset still’s disease Neutrophil activation Interleukin-1 Chemokine receptors |
| title | Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles |
| title_full | Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles |
| title_fullStr | Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles |
| title_full_unstemmed | Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles |
| title_short | Targeting neutrophil-driven inflammation in adult-onset still’s disease: molecular insights from gene expression profiles |
| title_sort | targeting neutrophil driven inflammation in adult onset still s disease molecular insights from gene expression profiles |
| topic | Adult-onset still’s disease Neutrophil activation Interleukin-1 Chemokine receptors |
| url | https://doi.org/10.1186/s13075-025-03598-5 |
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