Immune complex-mediated neutrophil activation in patients with polymyalgia rheumatica.
Immune complex-mediated neutrophil activation in patients with polymyalgia rheumatica.
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DOI：
10.1093/rheumatology/keac722
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发表时间：
2023-08-01
期刊：
影响因子：
5.5
通讯作者：
Lood, Christian
中科院分区：
文献类型：
--
作者：
Michailidou, Despina;Johansson, Linda;Kuley, Runa;Wang, Ting;Hermanson, Payton;Rantapaa-Dahlqvist, Solbritt;Lood, Christian
中性粒细胞在宿主防御中起重要作用。然而，中性粒细胞也与炎症和器官损伤有关。本研究的目的是评估中性粒细胞活化标志物是否在PMR中增加。使用ELISA测量健康个体（n = 30）和患有PMR的患者（n = 60）的血浆中的免疫复合物（IC）、钙卫蛋白和中性粒细胞胞外陷阱（NET）的水平，在发作时和用糖皮质激素治疗后。在存在FcγRIIA抑制性抗体的情况下评估血浆介导的中性粒细胞活化（IV.3）。PMR组血浆钙卫蛋白和NET水平显著升高（P < 0.001）。从机制上讲，中性粒细胞活化由血浆中存在的IC驱动，能够以Fcγ RIIA依赖性方式（P <0.01）上调中性粒细胞活化标志物CD66 b和CD11 b（P <0.0001）。值得注意的是，循环IC水平与血浆诱导的CD 66 b和CD 11 b相关（分别为r = 0.51，P = 0.004和r = 0.46，P = 0.01），并在糖皮质激素治疗后下降。与NET相比，糖皮质激素治疗后钙卫蛋白显著降低（P < 0.001），无重叠GCA的PMR患者的钙卫蛋白水平高于重叠疾病患者（P = 0.014）。有趣的是，肌肉骨骼受累与糖皮质激素治疗开始前钙卫蛋白水平升高相关（P = 0.036）。通过IC介导的FcγRIIA结合，PMR中的神经元活化（包括NET形成）增加。临床上，中性粒细胞活化与肌肉骨骼受累相关，钙卫蛋白（而非NET）是PMR患者治疗反应的生物标志物。总之，IC介导的中性粒细胞活化是PMR发病机制的中心过程，可识别潜在的新型治疗靶点（FcγRIIA）以及疾病监测的可溶性标志物（钙卫蛋白）。
Neutrophils are important in host defence. However, neutrophils are also linked to inflammation and organ damage. The purpose of this study was to assess whether markers of neutrophil activation are increased in PMR. Levels of immune complexes (IC), calprotectin and neutrophil extracellular traps (NETs) were measured in plasma of healthy individuals (n = 30) and patients with PMR (n = 60), at flare and upon treatment with glucocorticoids using ELISA. Plasma-mediated neutrophil activation was assessed in presence of an FcγRIIA inhibitory antibody (IV.3). Plasma levels of calprotectin and NETs were elevated in PMR (P < 0.001). Mechanistically, neutrophil activation was driven by ICs, present in plasma, able to up-regulate neutrophil activation markers CD66b and CD11b (P < 0.0001) in an FcγRIIA-dependent manner (P < 0.01). Of note, circulating levels of IC correlated with plasma induced CD66b and CD11b (r = 0.51, P = 0.004, and r = 0.46, P = 0.01, respectively) and decreased after glucocorticoid therapy. In contrast to NETs, calprotectin significantly decreased after glucocorticoid therapy (P < 0.001) and was higher in PMR without overlapping GCA compared with patients with overlapping disease (P = 0.014). Interestingly, musculoskeletal involvement was associated with elevated levels of calprotectin before initiation of glucocorticoid therapy (P = 0.036). Neutrophil activation, including NET formation, is increased in PMR, through IC-mediated engagement of FcγRIIA. Clinically, neutrophil activation is associated with musculoskeletal involvement, with calprotectin, but not NETs, being a biomarker of treatment response in PMR patients. In all, IC-mediated neutrophil activation is a central process in PMR pathogenesis identifying potential novel therapeutic targets (FcγRIIA), as well as soluble markers for disease monitoring (calprotectin).
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影响因子：
7.3
作者：
Michailidou D;Mustelin T;Lood C
通讯作者：
Lood C
影响因子：
7.3
作者：
Foell, D;Hernández-Rodríguez, J;Roth, J
通讯作者：
Roth, J
影响因子：
27.4
作者：
PARK, JR;JONES, JG;HAZLEMAN, BL
通讯作者：
HAZLEMAN, BL
DOI：
10.1084/jem.20161512
发表时间：
2017-07-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lood C;Arve S;Ledbetter J;Elkon KB
通讯作者：
Elkon KB
DOI：
10.4049/jimmunol.1201719
发表时间：
2012-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaplan MJ;Radic M
通讯作者：
Radic M