Lack of HLH in FMF
Abstract Background Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA), driven by excessive activation of T cells and macrophages, resulting in a cytokine storm. IFN-γ and IL-18 play crucial roles, with monocyte and macrophage hyperresponsi...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Pediatric Rheumatology Online Journal |
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| Online Access: | https://doi.org/10.1186/s12969-025-01064-9 |
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| author | Ozge Basaran Erdal Sag Elif Arslanoglu Aydın Busra Aydın Nur Kübra Tasdemir Elif Celikel Yagmur Bayındır Semanur Özdel Yelda Bilginer Alexei A Grom Seza Ozen |
| author_facet | Ozge Basaran Erdal Sag Elif Arslanoglu Aydın Busra Aydın Nur Kübra Tasdemir Elif Celikel Yagmur Bayındır Semanur Özdel Yelda Bilginer Alexei A Grom Seza Ozen |
| author_sort | Ozge Basaran |
| collection | DOAJ |
| description | Abstract Background Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA), driven by excessive activation of T cells and macrophages, resulting in a cytokine storm. IFN-γ and IL-18 play crucial roles, with monocyte and macrophage hyperresponsiveness to IFN-γ amplifying MAS-related inflammation. Familial Mediterranean Fever (FMF), an autosomal recessive disease, is characterized by recurrent fever episodes due to MEFV gene mutations. Despite intense inflammation in FMF, MAS is rare. This study aimed to compare in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-γ between sJIA/MAS and FMF patients. Methods Five sJIA/MAS and five FMF patients were included. PBMCs were stimulated in vitro with IFN-γ for 45 min. Levels of IFN-γ-induced chemokines CXCL9, CXCL10, and IL-18 in supernatants were measured using cytometric bead arrays before and after stimulation. Results PBMCs from MAS patients produced higher baseline CXCL9 levels compared to FMF patients in a flare, with differences increasing post-IFN-γ stimulation. IFN-γ stimulation also upregulated IL-18 production in MAS patients but not in FMF patients. Conclusion Enhanced responsiveness to IFN-γ distinguishes sJIA/MAS from FMF patients, which may explain the lower occurrence of MAS in FMF. |
| format | Article |
| id | doaj-art-c3ab1c4538db4e75b2aacd03b3dd7c05 |
| institution | Kabale University |
| issn | 1546-0096 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Pediatric Rheumatology Online Journal |
| spelling | doaj-art-c3ab1c4538db4e75b2aacd03b3dd7c052025-02-09T12:17:00ZengBMCPediatric Rheumatology Online Journal1546-00962025-02-012311610.1186/s12969-025-01064-9Lack of HLH in FMFOzge Basaran0Erdal Sag1Elif Arslanoglu Aydın2Busra Aydın3Nur Kübra Tasdemir4Elif Celikel5Yagmur Bayındır6Semanur Özdel7Yelda Bilginer8Alexei A Grom9Seza Ozen10Department of Pediatric Rheumatology, Hacettepe UniversityDepartment of Pediatric Rheumatology, Hacettepe UniversityDivision of Pediatric Rheumatology, University of Health Sciences, Etlik City HospitalPediatric Rheumatology Unit, Translational Medicine Laboratories, Hacettepe UniversityPediatric Rheumatology Unit, Translational Medicine Laboratories, Hacettepe UniversityDivision of Pediatric Rheumatology, University of Health Sciences, Ankara City HospitalDepartment of Pediatric Rheumatology, Hacettepe UniversityDivision of Pediatric Rheumatology, University of Health Sciences, Etlik City HospitalDepartment of Pediatric Rheumatology, Hacettepe UniversityDivision of Rheumatology, Cincinnati Children’s Hospital Medical Center, University of CincinnatiDepartment of Pediatric Rheumatology, Hacettepe UniversityAbstract Background Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA), driven by excessive activation of T cells and macrophages, resulting in a cytokine storm. IFN-γ and IL-18 play crucial roles, with monocyte and macrophage hyperresponsiveness to IFN-γ amplifying MAS-related inflammation. Familial Mediterranean Fever (FMF), an autosomal recessive disease, is characterized by recurrent fever episodes due to MEFV gene mutations. Despite intense inflammation in FMF, MAS is rare. This study aimed to compare in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-γ between sJIA/MAS and FMF patients. Methods Five sJIA/MAS and five FMF patients were included. PBMCs were stimulated in vitro with IFN-γ for 45 min. Levels of IFN-γ-induced chemokines CXCL9, CXCL10, and IL-18 in supernatants were measured using cytometric bead arrays before and after stimulation. Results PBMCs from MAS patients produced higher baseline CXCL9 levels compared to FMF patients in a flare, with differences increasing post-IFN-γ stimulation. IFN-γ stimulation also upregulated IL-18 production in MAS patients but not in FMF patients. Conclusion Enhanced responsiveness to IFN-γ distinguishes sJIA/MAS from FMF patients, which may explain the lower occurrence of MAS in FMF.https://doi.org/10.1186/s12969-025-01064-9CXCL-9CXCL-10Familial Mediterranean feverIL-18Macrophage activation syndrome |
| spellingShingle | Ozge Basaran Erdal Sag Elif Arslanoglu Aydın Busra Aydın Nur Kübra Tasdemir Elif Celikel Yagmur Bayındır Semanur Özdel Yelda Bilginer Alexei A Grom Seza Ozen Lack of HLH in FMF Pediatric Rheumatology Online Journal CXCL-9 CXCL-10 Familial Mediterranean fever IL-18 Macrophage activation syndrome |
| title | Lack of HLH in FMF |
| title_full | Lack of HLH in FMF |
| title_fullStr | Lack of HLH in FMF |
| title_full_unstemmed | Lack of HLH in FMF |
| title_short | Lack of HLH in FMF |
| title_sort | lack of hlh in fmf |
| topic | CXCL-9 CXCL-10 Familial Mediterranean fever IL-18 Macrophage activation syndrome |
| url | https://doi.org/10.1186/s12969-025-01064-9 |
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