Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis

Abstract

Background: Interstitial lung disease (ILD) is a relatively prevalent extra-articular manifestation of rheumatoid arthritis (RA) and contributes to significant morbidity and mortality. This study aimed to analyze the association between chitinase-3 like-protein-1(CHI3L1) and the presence of RA-ILD.

Methods: A total of 239 RA patients fulfilling the American Rheumatism Association (ACR) 1987 revised criteria were enrolled and subclassified as RA-ILD and RA-nILD based on the results of high-resolution computed tomography scans (HRCT) of the chest. The disease activity of RA was assessed by Disease Activity Score for 28 joints (DAS28) and categorized as high, moderate, low, and remission. Chemiluminescence immunoassays were applied to determine the serum levels of CHI3L1. Univariate analysis was performed and the receiver operating characteristics (ROC) curves were plotted to evaluate the correlation between RA-ILD and CHI3L1.

Results: Among the eligible RA patients studied, 60 (25.1%) patients were diagnosed with RA-ILD. Compared with RA-nILD, RA patients with ILD had significantly higher median age (median [IQR], 68.00 [62.00-71.75] vs 53.00 [40.00-63.00], p<0.001) and a higher proportion of males (21 (35.0%) vs 30 (16.8%), p=0.003). Notably, differences in DAS28 scores between the two groups were not observed. The serum level of CHI3L1 was significantly higher in RA-ILD patients (median [IQR], 69.69 [44.51-128.66] ng/ml vs 32.19 [21.63-56.99] ng/ml, p<0.001). Furthermore, the areas under the curve (AUC) of CHI3L1 attained 0.74 (95% confidence interval [CI], 0.68-0.81, p<0.001) in terms of identifying patients with RA-ILD from those without ILD. Similar trends were seen across the spectrum of disease activity based on DAS28-ESR.

Conclusion: Our findings of elevated serum CHI3L1 levels in RA-ILD patients suggest its possible role as a biomarker to detect RA-ILD noninvasively.

Keywords: biomarkers; chitinase-3 like-protein-1; interstitial lung disease; prediction; rheumatoid arthritis.

Figure 1

Serum level of CHI3L1 between RA-ILD and RA-nILD and among different disease activity subgroups. (A) RA patients with or without ILD. (B) RA patients with different activity states according to DAS28-ESR. (C) RA patients with different activity states according to DAS28-CRP. Violin plot depicts levels of CHI3L1 in individual serum samples from RA-ILD and RA-nILD. The dotted lines represent median and quartiles. The error bars show the median with 95% CI. P values were determined by Mann-Whitney U test (A) and Kruskal-Wallis test (B, C). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. "ns" means "no significance".

Figure 2

Performance characteristics of CHI3L1 levels in RA-ILD diagnosis. (A) ROC curves of CHI3L1 levels in RA-ILD and RA-nILD patients. (B) ROC curves of CHI3L1 levels in groups at different disease activity states based on DAS28-ESR. (C) ROC curves of CHI3L1 levels in groups at different disease activity states based on DAS28-CRP. AUC and 95% CI are shown in parentheses.