Changes and significance of lysyl oxidase-like protein 2,chemokine ligand-18 and chitinase-like protein 40 levels in patients with connective tissue disease complicated with interstitial lung disease before and after treatment

Zhao Yue; Yang Jinliang; Luo Huan; Xi Wenxiu; Wang Junlu; Zheng Xuejun

doi:10.3760/j.issn.1673-4777.2026.06.017

Abstract：Objective To investigate the changes and clinical significance of lysyl oxidase-like protein 2(LOXL2),chemokine ligand-18(CCL-18)and chitinase-like protein 40(YKL-40)levels in patients with connective tissue disease complicated with interstitial lung disease(CTD-ILD)before and after treatment.Methods A total of 90 patients with CTD-ILD admitted to the outpatient and inpatient Departments of Rheumatology and Immunology of The First Affiliated Hospital of Hebei North University from January 2022 to January 2023 were enrolled as observation group.Meanwhile,30 patients with simple connective tissue disease were set as case control group and 30 healthy subjects as healthy control group.According to pulmonary high-resolution CT(HRCT)scores before and after treatment,the 90 patients in the observation group were divided into improved group(38 cases),stable group(31 cases)and deteriorated group(21 cases).The levels of LOXL2,CCL-18,YKL-40 and HRCT scores were compared among all groups before treatment and 12 months after treatment.Spearman correlation analysis was used to analyze the correlation between serum LOXL2,CCL-18,YKL-40 levels and HRCT scores.Receiver operating characteristic(ROC)curve was established to analyze the predictive value of LOXL2,CCL-18 and YKL-40 levels before and after treatment for disease deterioration in CTD-ILD patients.Results Before treatment,the levels of LOXL2,CCL-18,YKL-40,SP-D and KL-6 in the observation group were higher than those in the case control group and healthy control group;the levels of the above indicators in the case control group were higher than those in the healthy control group(all P＜0.05).Before treatment and 12 months after treatment,the levels of LOXL2,CCL-18,YKL-40,SP-D,KL-6 and HRCT scores in the deteriorated group were higher than those in the stable group and improved group,and those in the stable group were higher than those in the improved group(all P＜0.05).In the improved group,the levels of LOXL2,CCL-18,YKL-40,SP-D,KL-6 and HRCT scores at 12 months after treatment were lower than those before treatment(all P＜0.05).Before treatment,LOXL2,CCL-18 and YKL-40 were positively correlated with HRCT scores(r=0.872,0.705,0.617,all P＜0.05).At 12 months after treatment,LOXL2,CCL-18 and YKL-40 were also positively correlated with HRCT scores(r=0.462,0.507,0.481,all P＜0.05).Before treatment,the area under the curve(AUC)of LOXL2,CCL-18 and YKL-40 for predicting disease deterioration in CTD-ILD patients was 0.871,0.880 and 0.792 respectively,and the AUC of combined prediction was 0.960,which was higher than that of single indicator prediction.At 12 months after treatment,the AUC of LOXL2,CCL-18 and YKL-40 for predicting disease deterio-ration was 0.862,0.869 and 0.761 respectively,and the AUC of combined prediction was 0.960,superior to single indicator prediction.Conclusions Serum LOXL2,CCL-18 and YKL-40 are highly expressed in CTD-ILD patients,which are among the pathogenic factors of ILD.Serum LOXL2,CCL-18 and YKL-40 are conducive to the early diagnosis of CTD-ILD and have important value in evaluating disease changes after treatment.