摘要
Abstract
Objective:Interstitial lung disease(ILD)is the most common visceral complication in systemic sclerosis(SSc)and a major cause of mortality.However,studies on biomarkers for SSc-ILD are limited,and most international guidelines do not yet include biomarkers for diagnosing or assessing disease severity in SSc-ILD.This study aims to explore the clinical significance of several biomarkers in diagnosing and evaluating disease activity in SSc-ILD.
Methods:A total of 186 hospitalized patients diagnosed with SSc at Xiangya Hospital of Central South University between January 2019 and March 2023 were retrospectively included.High-resolution computed tomography(HRCT)was used to determine ILD status,classifying patients into a SSc-ILD group(n=128)and a SSc-non-ILD(n=58)group.Additionally,56 healthy individuals were recruited as a normal control(NC)group.Demographic and clinical data,treatment regimens,laboratory results,pulmonary function,HRCT images,and serum samples were collected.Serum levels of Dickkopf-1(DKK1),CC chemokine ligand 18(CCL18),and CCL28 were measured using enzyme-linked immunosorbent assay(ELISA).Differences in DKK1,CCL18,CCL28,Krebs von den Lungen-6(KL-6),and ferritin were compared between the SSc-ILD and SSc-non-ILD groups.Correlations between these biomarkers and HRCT scores or pulmonary function were also analyzed.
Results:There were no significant differences in age or gender among the 3 groups(all P>0.05).Compared to the SSc-non-ILD group,patients in the SSc-ILD group had longer disease duration,higher incidence of Raynaud's phenomenon and fingertip atrophy,and more frequent use of glucocorticoids and nintedanib(all P<0.05).DKK1 levels were lower in the SSc-ILD group than in the NC group(P<0.01).CCL18 levels were significantly elevated in both SSc groups compared to the NC group(P<0.001).KL-6 levels were significantly higher in the SSc-ILD group than in the SSc-non-ILD group(P<0.001),while lactate dehydrogenase(LDH)levels were significantly lower(P=0.022);no significant differences were found in other indices(P>0.05).The optimal cutoff for KL-6 was 561.25 U/mL,yielding a sensitivity of 65.4%and specificity of 72.4%for ILD diagnosis[area under the curve(AUC)=0.722,P<0.001].KL-6 was positively correlated with total ground glass(t-GG),total fibrosis(t-Fib),total bronchiectasis(t-B),total honeycombing(t-HC),and overall HRCT scores(all P<0.05).CCL18 was positively correlated with t-GG and t-Fib(both P<0.05).KL-6 was negatively correlated with forced vital capacity as a percentage of predicted value(FVC%)and DLCO%(both P<0.05).
Conclusion:KL-6 is a biomarker for diagnosis of SSc-ILD and assessment of disease activity.Compared with KL-6,DKK1,CCL18 and CCL28 have no advantage in the diagnosis and disease activity assessment of SSc-ILD.关键词
系统性硬化病/肺间质病变/Dickkopf相关蛋白1/CC趋化因子配体18/CC趋化因子配体28/涎液化糖链抗原-6Key words
systemic sclerosis/interstitial lung disease/Dickkopf 1/CC chemokine ligand 18/CC chemokine ligand 28/krebs von den lungen-6
