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白细胞动力学揭示巨细胞动脉炎和风湿性多肌痛中持续的髓系优势。

Leukocyte Dynamics Reveal a Persistent Myeloid Dominance in Giant Cell Arteritis and Polymyalgia Rheumatica.

机构信息

Vasculitis Expertise Centre Groningen, Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.

出版信息

Front Immunol. 2019 Aug 22;10:1981. doi: 10.3389/fimmu.2019.01981. eCollection 2019.

DOI:10.3389/fimmu.2019.01981
PMID:31507597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6714037/
Abstract

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are inflammatory diseases requiring long-term glucocorticoid treatment. Limited data on dynamics in leukocyte counts before, during and after treatment are available. Leukocyte counts were measured, as cellular markers of inflammation, at fixed time points in our prospectively studied cohort of pre-treatment glucocorticoid-naive GCA ( = 42) and PMR ( = 31) patients. Values were compared with age-matched healthy controls (HCs; = 51) and infection controls ( = 16). We report that before start of treatment monocyte and neutrophil counts were higher in GCA and PMR patients than in HCs, while NK- and B-cell counts were lower. C-reactive protein (CRP) levels correlated positively with monocyte counts in GCA, and negatively with B-cell and NK-cell counts in PMR. During glucocorticoid treatment, myeloid subsets remained elevated whereas lymphoid subsets tended to fluctuate. Interestingly, erythrocyte sedimentation rate (ESR) outperformed CRP as marker for relapses in GCA. We defined stable treatment-free remission groups in both GCA and PMR. GCA patients in treatment-free remission still demonstrated elevated monocytes, neutrophils, ESR, and platelets. PMR patients in treatment-free remission had normalized levels of inflammation markers, but did have elevated monocytes, lowered CD8+ T-cell counts and lowered NK-cell counts. Finally, we showed that low hemoglobin level was predictive for long-term GC treatment in PMR. Overall, leukocyte composition shifts toward the myeloid lineage in GCA and PMR. This myeloid profile, likely induced by effects of inflammation on hematopoietic stem cell differentiation, persisted during glucocorticoid treatment. Surprisingly, the myeloid profile was retained in treatment-free remission, which may reflect ongoing subclinical inflammation.

摘要

巨细胞动脉炎(GCA)和多发性肌炎(PMR)是需要长期糖皮质激素治疗的炎症性疾病。关于治疗前、治疗中和治疗后白细胞计数变化的有限数据。我们对皮质激素初治的 GCA(=42)和 PMR(=31)患者前瞻性研究队列中的白细胞计数进行了固定时间点测量,作为炎症的细胞标志物。将这些数值与年龄匹配的健康对照组(HCs;=51)和感染对照组(=16)进行比较。我们报告称,在开始治疗之前,GCA 和 PMR 患者的单核细胞和中性粒细胞计数高于 HCs,而 NK 细胞和 B 细胞计数较低。GCA 患者的 C 反应蛋白(CRP)水平与单核细胞计数呈正相关,PMR 患者的 B 细胞和 NK 细胞计数与 CRP 呈负相关。在糖皮质激素治疗期间,髓系亚群仍然升高,而淋巴亚群则趋于波动。有趣的是,红细胞沉降率(ESR)在 GCA 中比 CRP 更能作为复发的标志物。我们在 GCA 和 PMR 中定义了稳定的无治疗缓解组。无治疗缓解的 GCA 患者仍然表现出升高的单核细胞、中性粒细胞、ESR 和血小板。无治疗缓解的 PMR 患者的炎症标志物水平正常,但仍有升高的单核细胞、降低的 CD8+T 细胞计数和降低的 NK 细胞计数。最后,我们表明 PMR 患者的低血红蛋白水平与长期 GC 治疗相关。总的来说,GCA 和 PMR 患者的白细胞组成向髓系转移。这种髓系表型可能是由炎症对造血干细胞分化的影响引起的,在糖皮质激素治疗期间持续存在。令人惊讶的是,在无治疗缓解期间保留了髓系表型,这可能反映了持续的亚临床炎症。

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Markers of angiogenesis and macrophage products for predicting disease course and monitoring vascular inflammation in giant cell arteritis.用于预测巨细胞动脉炎疾病进程和监测血管炎症的血管生成标志物和巨噬细胞产物
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Massive B-Cell Infiltration and Organization Into Artery Tertiary Lymphoid Organs in the Aorta of Large Vessel Giant Cell Arteritis.
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Immuno-monitoring reveals an extended subclinical disease activity in tocilizumab-treated giant cell arteritis.免疫监测揭示托珠单抗治疗巨细胞动脉炎的亚临床疾病活动延长。
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