De Paepe Boel, Bracke Ken R, De Bleecker Jan L
Department of Neurology, Ghent University Hospital, B-9000 Ghent, Belgium.
Neuromuscular Reference Center, Ghent University Hospital, B-9000 Ghent, Belgium.
Brain Sci. 2023 Sep 25;13(10):1369. doi: 10.3390/brainsci13101369.
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.
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。
