Maharjan Anu S, Amjadi Sogol S, Jaskowski Troy D, La'ulu Sonia L, Lebiedz-Odrobina Dorota, Frech Tracy M, Tebo Anne E
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
ARUP Laboratories, Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
Clin Chem Lab Med. 2024 Nov 29;63(4):797-804. doi: 10.1515/cclm-2024-1048. Print 2025 Mar 26.
This study aimed to determine the clinical significance of Krebs von den Lungen-6 (KL-6), surfactant proteins A (SP-A) and D (SP-D) in the evaluation and management of interstitial lung disease (ILD).
Serum KL-6, SP-A, SP-D levels were measured in 122 unique consecutive patients referred for connective tissue disease (CTD) associated ILD (CTD-ILD) autoantibodies and 120 "healthy" controls. Patients' charts were retrospectively reviewed and categorized as ILD and non-ILD or CTD-ILD and other ILD. All biomarkers were evaluated for diagnosis and moderate vs. severe ILD based on high-resolution computed tomography (HRCT).
ILD was diagnosed in 52 % (n=64) and non-ILD in 48 % (n=58). ILD patients were categorized as other ILD (61 %, n=39) or CTD-ILD (39 %, n=25). Patients with ILD had significantly elevated levels of SP-A (p<0.02), KL-6 or SP-D (both p<0.0001) when compared to those with non-ILD. The mean levels of all biomarkers were significantly elevated levels in the ILD compared to non-ILD group (p<0.0001). No significant difference in biomarker levels between CTD-ILD and other ILD groups (p≥0.900). Biomarkers had comparable specificities (89-93 %) however; sensitivities were variable at 75 , 77 and 17 % for KL-6, SP-D and SP-A, respectively. Combination of KL-6 and SP-D yielded comparable diagnostic accuracy to all biomarkers with median levels significantly higher in patients with severe vs. mild disease.
KL-6 and SP-D levels are elevated in ILD and therefore contribute to the diagnosis and risk stratification for patient management.
本研究旨在确定克雷布斯-冯-登-龙根-6(KL-6)、表面活性蛋白A(SP-A)和D(SP-D)在间质性肺疾病(ILD)评估和管理中的临床意义。
对122例因结缔组织病(CTD)相关ILD(CTD-ILD)自身抗体前来就诊的连续患者和120例“健康”对照者检测血清KL-6、SP-A、SP-D水平。对患者病历进行回顾性审查,并分为ILD组和非ILD组或CTD-ILD组和其他ILD组。基于高分辨率计算机断层扫描(HRCT)对所有生物标志物进行诊断评估以及区分中度与重度ILD。
52%(n = 64)患者被诊断为ILD,48%(n = 58)为非ILD。ILD患者被分为其他ILD(61%,n = 39)或CTD-ILD(39%,n = 25)。与非ILD患者相比,ILD患者的SP-A水平显著升高(p < 0.02),KL-6或SP-D水平均显著升高(均p < 0.0001)。与非ILD组相比,ILD组所有生物标志物的平均水平均显著升高(p < 0.0001)。CTD-ILD组和其他ILD组之间生物标志物水平无显著差异(p≥0.900)。然而,生物标志物具有相当的特异性(89 - 93%);KL-6、SP-D和SP-A的敏感性分别为75%、77%和17%,各不相同。KL-6和SP-D联合检测的诊断准确性与所有生物标志物相当,重度与轻度疾病患者的中位数水平显著更高。
ILD患者的KL-6和SP-D水平升高,因此有助于ILD的诊断和患者管理的风险分层。