Cells · 2026
Disrupted Neutrophil and Myeloid Cell Homeostasis and Effector Dysfunction Drive Vasculopathy in Idiopathic Inflammatory Myopathies.
СтатьяНазвание и аннотация: Перевод в очереди
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Carrillo-Vázquez Daniel Alberto, Alcalá-Carmona Beatriz, Balderas Miranda Jennifer Tiaré, Reyna-Juárez Yatzil, Ostos-Prado María José, Cassiano-Quezada Fabiola, Govea-Peláez Samuel, Mejía-Domínguez Nancy R, Juárez-Vega Guillermo, Santana-De Anda Karina, Torres-Ruiz Jiram, Gómez-Martín Diana
Аннотация
BACKGROUND: Neutrophils play a role in idiopathic inflammatory myopathies (IIMs), especially in vasculopathic manifestations. While neutrophil extracellular traps (NETs) and low-density granulocytes (LDGs) have been described, the functional relevance of other subsets-such as naïve neutrophils, reverse transendothelial migration neutrophils (rTEM), myeloid-derived suppressor cells (MDSCs), and regulatory neutrophils-and their association with vasculopathy remains unknown.
OBJECTIVE: We aimed to characterize the phenotypic and functional profile of neutrophil subsets and their association with vasculopathic manifestations in IIM, adjusting for disease activity.
METHODS: We conducted a cross-sectional, single-center study including 59 IIM patients diagnosed by muscle biopsy and fulfilling 2017 ACR/EULAR criteria. Flow cytometry was used to immunophenotype myeloid subsets, and functional assays assessed phagocytosis and respiratory burst. Patients were stratified by clinical activity and presence of vasculopathy.
RESULTS: Vasculopathic patients showed expansion of LDGs (p = 0.0092), granulocytic and monocytic MDSCs expressing Arginase-1 (p = 0.0078, p = 0.0003) and PD-L1 (p = 0.0258, p = 0.0087), and rTEM neutrophils (p = 0.0775). In contrast, they exhibited a reduction in naïve neutrophils (p = 0.0004), phagocytosis (p < 0.0001) and respiratory burst (p = 0.0006). Multivariate analysis identified naïve neutrophils and activated CD177+ neutrophils as independent predictors of vasculopathy. A positive correlation between activated and naïve neutrophils were observed in patients with vasculopathic features (r = 0.43; p < 0.05).
CONCLUSIONS: IIM patients with vasculopathic features display a distinct immune profile characterized by an imbalance between proinflammatory and regulatory neutrophil subsets, alongside persistent functional impairment.
OBJECTIVE: We aimed to characterize the phenotypic and functional profile of neutrophil subsets and their association with vasculopathic manifestations in IIM, adjusting for disease activity.
METHODS: We conducted a cross-sectional, single-center study including 59 IIM patients diagnosed by muscle biopsy and fulfilling 2017 ACR/EULAR criteria. Flow cytometry was used to immunophenotype myeloid subsets, and functional assays assessed phagocytosis and respiratory burst. Patients were stratified by clinical activity and presence of vasculopathy.
RESULTS: Vasculopathic patients showed expansion of LDGs (p = 0.0092), granulocytic and monocytic MDSCs expressing Arginase-1 (p = 0.0078, p = 0.0003) and PD-L1 (p = 0.0258, p = 0.0087), and rTEM neutrophils (p = 0.0775). In contrast, they exhibited a reduction in naïve neutrophils (p = 0.0004), phagocytosis (p < 0.0001) and respiratory burst (p = 0.0006). Multivariate analysis identified naïve neutrophils and activated CD177+ neutrophils as independent predictors of vasculopathy. A positive correlation between activated and naïve neutrophils were observed in patients with vasculopathic features (r = 0.43; p < 0.05).
CONCLUSIONS: IIM patients with vasculopathic features display a distinct immune profile characterized by an imbalance between proinflammatory and regulatory neutrophil subsets, alongside persistent functional impairment.