Academic Journal
Monocyte STAT1 phosphorylation and treatment response of JAK inhibitors in chronic nonbacterial osteomyelitis
| Title: | Monocyte STAT1 phosphorylation and treatment response of JAK inhibitors in chronic nonbacterial osteomyelitis |
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| Authors: | Motoshi Sonoda, Keishiro Kinoshita, Nobutaka Harada, Sungyeon Park, Shunichi Adachi, Yutaro Yada, Katsuhide Eguchi, Toshifumi Fujiwara, Makiko Kido-Nakahara, Noriko Kinjo, Masataka Ishimura, Shouichi Ohga |
| Source: | Pediatric Rheumatology Online Journal, Vol 23, Iss 1, Pp 1-11 (2025) |
| Publisher Information: | BMC, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Pediatrics LCC:Diseases of the musculoskeletal system |
| Subject Terms: | Autoinflammation, CNO, STAT1 phosphorylation, JAK inhibitors, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935 |
| More Details: | Abstract Background Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory disease of unknown cause, predominantly affecting teens and young adults. The early diagnosis and management are challenging due to the lack of reliable diagnostic markers and the occasional intractable cases despite conventional anti-inflammatory treatments. Janus kinase (JAK) inhibitors have recently shown potential utility; however, reports on their use for pediatric patients with CNO remain limited, and no established biomarkers exist to monitor disease activity. We aimed to investigate the pathophysiology of CNO and explore the rapid testing methods for accurate diagnosis and also assessing the disease activity. Methods We assessed intracellular phosphorylation of signal transducer and activator of transcription 1 (pSTAT1) in peripheral blood monocytes or T cells following interferon-gamma (IFNγ) stimulation, using flow cytometry in 9 patients under 15 years old with CNO. The pSTAT1 expression levels were compared with those in patients with STAT1-gain of function (STAT1-GOF) mutations (n = 5), other autoinflammatory diseases (n = 7), and healthy controls. Clinical and immunological data were monitored in 4 patients with intractable CNO treated with adjunctive JAK inhibitors, focusing on scoring scales, imaging data, lymphocyte subsets, cytokine profiles, and pSTAT1 levels. Results Monocyte pSTAT1 expression after IFNγ stimulation was elevated at diagnosis or during active CNO, similar to levels observed in STAT1-GOF cases. The pSTAT1 levels in CNO patients were significantly higher than those in other autoinflammatory diseases (p = 0.024) or controls (p |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1546-0096 |
| Relation: | https://doaj.org/toc/1546-0096 |
| DOI: | 10.1186/s12969-025-01059-6 |
| Access URL: | https://doaj.org/article/8b127507a4e34d7caa94ce68cbeb6576 |
| Accession Number: | edsdoj.8b127507a4e34d7caa94ce68cbeb6576 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 15460096 |
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| DOI: | 10.1186/s12969-025-01059-6 |
| Published in: | Pediatric Rheumatology Online Journal |
| Language: | English |