Department of Pneumology, Medical University of Lodz, Lodz, Poland.
Department of Pathobiology of Respiratory Diseases, Medical University of Lodz, Lodz, Poland.
Front Immunol. 2022 Feb 10;13:760776. doi: 10.3389/fimmu.2022.760776. eCollection 2022.
Although chitin is absent in humans, chitinases are present in healthy subjects and show dysregulated expression in a variety of diseases resulting from abnormal tissue injury and repair responses. It was shown that chitotriosidase (chitinase 1/CHIT1) and structurally-related chitinase 3-like 1 protein (CHI3L1/YKL-40) play important roles in the pathobiology of idiopathic pulmonary fibrosis (IPF), however little is known about their longitudinal serum levels and relationship to clinical measures in IPF.
The present study is the first to evaluate serial measurements of serum CHIT1 activity and YKL-40 concentrations in patients with IPF starting antifibrotic treatment and followed up for 24 months. In addition, baseline serum CHIT1 and YKL-40 were compared between patients with IPF and control subjects, and possible CHIT1 and YKL-40 relationships to longitudinal clinical assessments in IPF were explored.
Baseline serum CHIT1 activity and YKL-40 concentrations were significantly elevated in patients with IPF compared to control subjects and showed similar discriminatory ability in distinguishing IPF from controls. No significant differences between the median serum CHIT1 activity and YKL-40 concentration measured over a study follow-up were noted. We found significantly elevated baseline serum CHIT1 activity in the progressors compared with the stables in the first year, while significantly increased baseline serum CHIT1 activity was noted in the stables compared to the progressors in the second year. Additionally, we observed a significant negative correlation between a change in serum YKL-40 concentration and a change in forced vital capacity (FVC) % predicted (% pred.) in the stables subgroup, whereas, a change in serum CHIT1 activity correlated negatively with a change in FVC% pred. in the progressors subgroup.
This explorative study findings add further evidence that CHIT1 and YKL-40 are upregulated in patients with IPF, and suggest that longitudinally stable serum CHIT1 activity and YKL-40 concentration levels may potentially be associated with the antifibrotic treatment response. In addition, our findings are supporting the possible role of CHIT1 and YKL-40 as candidate diagnostic and prognostic biomarkers in IPF. Further research is needed to validate present study findings.
尽管人类体内不存在几丁质，但健康个体中存在几丁质酶，且其表达失调与各种疾病相关，这些疾病是由异常的组织损伤和修复反应引起的。研究表明，壳三糖酶（几丁质酶 1/CHIT1）和结构相关的几丁质酶 3 样蛋白 1（CHI3L1/YKL-40）在特发性肺纤维化（IPF）的病理生物学中发挥着重要作用，然而，关于它们在 IPF 中的纵向血清水平及其与临床指标的关系，我们知之甚少。
本研究首次评估了开始抗纤维化治疗的 IPF 患者的血清 CHIT1 活性和 YKL-40 浓度的系列测量值，并随访 24 个月。此外，比较了 IPF 患者和对照组的基线血清 CHIT1 和 YKL-40，并探讨了 CHIT1 和 YKL-40 与 IPF 纵向临床评估的可能关系。
与对照组相比，IPF 患者的基线血清 CHIT1 活性和 YKL-40 浓度显著升高，并且在区分 IPF 与对照组方面具有相似的区分能力。在研究随访期间，未观察到中位血清 CHIT1 活性和 YKL-40 浓度的显著差异。我们发现，在第一年中，进展者的基线血清 CHIT1 活性明显高于稳定者，而在第二年中，稳定者的基线血清 CHIT1 活性明显高于进展者。此外，我们观察到在稳定者亚组中，血清 YKL-40 浓度的变化与用力肺活量（FVC）%预计值（% pred.）的变化呈显著负相关，而在进展者亚组中，血清 CHIT1 活性的变化与 FVC% pred.的变化呈显著负相关。
这项探索性研究结果进一步证明 CHIT1 和 YKL-40 在 IPF 患者中上调，并表明纵向稳定的血清 CHIT1 活性和 YKL-40 浓度水平可能与抗纤维化治疗反应相关。此外，我们的研究结果支持 CHIT1 和 YKL-40 作为 IPF 候选诊断和预后生物标志物的可能作用。需要进一步的研究来验证本研究的结果。
