Costa Júlia, Gromicho Marta, Pronto-Laborinho Ana, Almeida Conceição, Gomes Ricardo A, Guerreiro Ana C L, Oliva Abel, Pinto Susana, de Carvalho Mamede
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157 Oeiras, Portugal.
Instituto de Fisiologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Diagnostics (Basel). 2021 Jul 5;11(7):1210. doi: 10.3390/diagnostics11071210.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2-5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.
肌萎缩侧索硬化症（ALS）是一种神经退行性神经肌肉疾病，会影响控制随意肌的运动神经元。发病后生存期通常为2至5年，死亡原因是呼吸衰竭。生物标志物的鉴定对于疾病诊断以及基于例如进展速度的患者分层非常有用，这对治疗试验具有重要意义。神经丝已经是有前景的ALS标志物，最近，几丁质酶已成为该疾病新的标志物靶点。在此，我们研究了脑脊液（CSF）几丁质酶作为ALS潜在标志物的情况。通过酶联免疫吸附测定（ELISA）对34例ALS患者和24例患有其他神经系统疾病的对照患者的脑脊液中的壳三糖苷酶（CHIT1）、几丁质酶-3样蛋白1（CHI3L1）、几丁质酶-3样蛋白2（CHI3L2）以及基准标志物磷酸化神经丝重链（pNFH）进行了定量。还通过超高效液相色谱-质谱联用（UHPLC-质谱）对脑脊液进行了分析。发现所有三种几丁质酶以及pNFH均与疾病进展速度相关。此外，CHIT1在ALS患者中升高，具有较高的诊断性能，pNFH也是如此。另一方面，CHIT1与用力肺活量（FVC）相关。三种几丁质酶与pNFH相关，表明变性与神经炎症之间存在关联。总之，我们的结果支持CHIT1作为诊断和进展速度生物标志物的价值及其作为呼吸功能标志物的潜力。这些结果为探索几丁质酶作为生物标志物及其在ALS中的功能相关性开辟了新的视角。
