Neutrophil activation biomarker pentraxin 3 for diagnosis and monitoring of macrophage activation syndrome occurrence in adult-onset Still's disease.
J Autoimmun
; 144: 103182, 2024 04.
Article
em En
| MEDLINE
| ID: mdl-38460457
ABSTRACT
Macrophage activation syndrome (MAS) is a potentially fatal consequence of adult-onset Still's disease (AOSD), driven by a cytokine storm. Efficient early diagnosis of AOSD-associated MAS requires a sensitive and specific biomarker. In this study, we demonstrated that pentraxin 3 (PTX3), an acute phase protein, was associated with AOSD disease activity and served as a biomarker for AOSD-MAS. PTX3 levels were significantly increased in AOSD patients compared to other autoimmune diseases and healthy controls. Plasma PTX3 levels showed positive correlations with inflammatory markers, the systemic score and the HScore. In active AOSD with MAS, PTX3 levels were higher compared to those in non-AOSD haemophagocytic lymphohistiocytosis (HLH) patients. Moreover, the PTX3's area under the curve value for distinguishing AOSD with MAS exceeded that of soluble interleukin-2 receptor, ferritin and C-reactive protein. Furthermore, plasma levels of PTX3 were associated with circulating NET-DNA levels. To fully understand the underlying mechanism of PTX3 prompting AOSD and AOSD-MAS progression, we discovered that neutrophils exhibited enhanced NET formation and mitogen-activated protein kinases (MAPK) pathway activation upon PTX3 stimulation. More importantly, PTX3-induced NET formation was effectively dampened by MAPK pathway inhibitors. These findings collectively revealed that PTX3 has a favorable correlation with disease activity and may serve as a potential biomarker to differentiate AOSD patients with MAS. Additionally, PTX3 induces NET release via the MAPK pathway, suggesting a pathogenic role in AOSD-MAS.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Componente Amiloide P Sérico
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Doença de Still de Início Tardio
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Síndrome de Ativação Macrofágica
Limite:
Adult
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article