Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy.
Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy.
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DOI：
10.3233/jnd-210711
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发表时间：
2022
影响因子：
3.3
通讯作者：
Sacconi S
中科院分区：
文献类型：
--
作者：
Gros M;Nunes AM;Daoudlarian D;Pini J;Martinuzzi E;Barbosa S;Ramirez M;Puma A;Villa L;Cavalli M;Grecu N;Garcia J;Siciliano G;Solé G;Juntas-Morales R;Jones PL;Jones T;Glaichenhaus N;Sacconi S
面肩肱型肌营养不良症（FSHD）是成人最常见的肌病之一，表现为进行性的、经常不对称的典型肌肉型受累。FSHD与染色体4 q上多态性D4 Z4重复的表观遗传去抑制相关，导致骨骼肌中DUX 4逆转录基因毒性表达。鉴定与疾病严重程度相关的生物标志物将有助于临床管理和评估潜在的FSHD治疗剂的功效。本研究的目的是分析血清细胞因子，以确定一个大型FSHD成人患者队列中的潜在生物标志物。我们回顾性地测量了100例经遗传学证实的成人FSHD 1患者血清中20种促炎性和调节性细胞因子的水平。研究了细胞因子浓度与各种临床评分之间的相关性。然后，我们在经验证的FSHD样小鼠模型中测量血清和肌肉白细胞介素6（IL-6）水平，包括严重程度和DUX 4表达。IL-6被鉴定为浓度与几种临床严重程度和功能评分相关的唯一细胞因子，所述临床严重程度和功能评分包括临床严重程度评分、手动肌肉测试总分、布鲁克和瓦尔斯评分。此外，FSHD患者的总体IL-6水平是对照组的两倍多，而具有较轻表型的患者的IL-6血清浓度低于具有严重肌无力的患者。最后，FSHD样小鼠模型分析证实IL-6水平与疾病严重程度和DUX 4表达正相关。因此，血清IL-6显示出作为FSHD 1成人患者大队列中FSHD严重程度的血清生物标志物的前景。
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies in adults, displaying a progressive, frequently asymmetric involvement of a typical muscles’ pattern. FSHD is associated with epigenetic derepression of the polymorphic D4Z4 repeat on chromosome 4q, leading to DUX4 retrogene toxic expression in skeletal muscles. Identifying biomarkers that correlate with disease severity would facilitate clinical management and assess potential FSHD therapeutics’ efficacy. This study purpose was to analyze serum cytokines to identify potential biomarkers in a large cohort of adult patients with FSHD. We retrospectively measured the levels of 20 pro-inflammatory and regulatory cytokines in sera from 100 genetically confirmed adult FSHD1 patients. Associations between cytokine concentrations and various clinical scores were investigated. We then measured serum and muscle interleukin 6 (IL-6) levels in a validated FSHD-like mouse model, ranging in severity and DUX4 expression. IL-6 was identified as the only cytokine with a concentration correlating with several clinical severity and functional scores, including Clinical Severity Score, Manual Muscle Testing sum score, Brooke and Vignos scores. Further, FSHD patients displayed overall IL-6 levels more than twice high as control, and patients with milder phenotypes exhibited lower IL-6 serum concentration than those with severe muscular weakness. Lastly, an FSHD-like mouse model analysis confirmed that IL-6 levels positively correlate with disease severity and DUX4 expression. Serum IL-6, therefore, shows promise as a serum biomarker of FSHD severity in a large cohort of FSHD1 adult patients.