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回顾性研究表明,趋化因子CXCL10和细胞因子GDF15的血清水平有助于散发性包涵体肌炎和免疫介导的坏死性肌病的诊断。

Retrospective Study Shows That Serum Levels of Chemokine CXCL10 and Cytokine GDF15 Support a Diagnosis of Sporadic Inclusion Body Myositis and Immune-Mediated Necrotizing Myopathy.

作者信息

De Paepe Boel, Bracke Ken R, De Bleecker Jan L

机构信息

Department of Neurology, Ghent University Hospital, B-9000 Ghent, Belgium.

Neuromuscular Reference Center, Ghent University Hospital, B-9000 Ghent, Belgium.

出版信息

Brain Sci. 2023 Sep 25;13(10):1369. doi: 10.3390/brainsci13101369.

Abstract

The implementation of novel blood-based biomarkers is desired to reduce the diagnostic delay and burden for myositis patients. In this retrospective study, the potential of C-X-C motif chemokine ligand 10 (CXCL10) and growth differentiation factor 15 (GDF15) was explored in an established patient cohort diagnosed with immune-mediated necrotizing myopathy (IMNM; n = 21), sporadic inclusion body myositis (IBM; n = 18), overlap myositis (OM; n = 3), dermatomyositis (DM; n = 2), and anti-synthetase syndrome (ASS; n = 1), comparing these results with healthy controls (n = 10) and patients with a hereditary neuromuscular disorder (n = 14). CXCL10 and GDF15 were quantified in sera with enzyme-linked immunosorbent assays and immunolocalized in skeletal muscle tissue. In myositis patients, serum CXCL10 levels were significantly increased 9.6-fold compared to healthy controls and 4.2-fold compared to disease controls. Mean levels of CXCL10 were 929 ± 658 pg/mL of serum in IBM and 425 ± 324 pg/mL of serum in IMNM. With the threshold set to 180 pg/mL of CXCL10, myositis patients could be differentiated from healthy and disease controls with a sensitivity of 0.80 and a specificity of 0.71. Incorporating a threshold of 300 pg/mL for GDF15 reduced false negatives to two IMNM patients only. Subsets of muscle-infiltrating immune cells expressed CXCL10, and serum levels correlated with muscle inflammation grade. We propose adding circulating CXCL10 and GDF15 to the blood-based diagnostic toolkit for myositis as a valuable patient-friendly approach.

摘要

为减少肌炎患者的诊断延迟和负担,人们期望采用新型血液生物标志物。在这项回顾性研究中,我们在一个已确诊的患者队列中探索了C-X-C基序趋化因子配体10(CXCL10)和生长分化因子15(GDF15)的潜力,该队列包括免疫介导的坏死性肌病(IMNM;n = 21)、散发性包涵体肌炎(IBM;n = 18)、重叠性肌炎(OM;n = 3)、皮肌炎(DM;n = 2)和抗合成酶综合征(ASS;n = 1)患者,并将这些结果与健康对照者(n = 10)和遗传性神经肌肉疾病患者(n = 14)进行比较。通过酶联免疫吸附测定法定量血清中的CXCL10和GDF15,并在骨骼肌组织中进行免疫定位。在肌炎患者中,血清CXCL10水平与健康对照者相比显著升高9.6倍,与疾病对照者相比升高4.2倍。IBM患者血清中CXCL10平均水平为929±658 pg/mL,IMNM患者血清中CXCL10平均水平为425±324 pg/mL。将CXCL10阈值设定为180 pg/mL时,肌炎患者与健康对照者及疾病对照者的鉴别灵敏度为0.80,特异性为0.71。将GDF15阈值设定为300 pg/mL时,仅将两名IMNM患者的假阴性结果减少。肌肉浸润免疫细胞亚群表达CXCL10,血清水平与肌肉炎症分级相关。我们建议将循环CXCL10和GDF15添加到基于血液的肌炎诊断工具包中,作为一种对患者有价值且友好的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27f/10605230/ca658853c2ac/brainsci-13-01369-g001.jpg

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