Chitinase-3 like-protein-1 may serve as a potential biomarker in RA patients with interstitial lung disease

Interstitial lung disease (ILD) is a common complication of rheumatoid arthritis (RA), which can lead to serious health problems and even death. A recent article published in Frontiers in Immunology reported increased levels of chitinase-3 like-protein-1 (CHI3L1) in patients with RA-ILD and suggested its promising role as a biomarker. 

The study conducted at the Department of Rheumatology at Peking Union Medical College Hospital in Beijing, China, Dr. Yu and colleagues analyzed the serum CHI3L1 levels of 239 RA patients from 2019 to 2021. Patients were divided into two groups based on the presence of ILD: RA-ILD (60, 25.1%) or RA patients without ILD (RA-nILD) (179, 74.9%). The results showed that patients with RA-ILD had significantly higher levels of CHI3L1 compared to RA-nILD (median, 69.69 vs. 32.19, P < 0.001). When assessing the potential use of CHI3L1 as a biomarker for RA-ILD, ROC analysis revealed strong predictive performance with an AUC of 0.74 (95% CI, 0.68-0.81). To confirm these findings, cross-validation of the ROC curve was performed. A positive cut-off value of ≥44.20 ng/mL was determined based on a sensitivity of 76.67%, specificity of 62.57%, and the Youden Index. CHI3L1 positivity was more frequently observed in RA-ILD patients (46 [76.67%] vs. 70 [39.11%], P = 0.006). 

Hozumi et al. suggested Chitinase-3-like-1 protein (YKL-40) as a promising biomarker for assessing polymyositis (PM) / dermatomyositis (DM)–ILD activity/severity and predicting disease prognosis. In a study involving 69 PM/DM-ILD patients and 34 healthy controls, a significant elevation in YKL-40 levels was reported in PM/DM-ILD patients compared to the healthy controls. Serum YKL-40 was significantly associated with lower arterial oxygen pressure and lower percent-predicted diffusing capacity of the lungs for carbon monoxide (DLCO). Immunohistochemistry analysis also revealed increased YKL-40 expression in intraalveolar macrophages and alveolar epithelial cells in patients with PM/DM-IL. 

The study findings highlight the association between CHI3L1 and RA-ILD, suggesting the potential of CHI3L1 as a valuable biomarker for RA-ILD. Further research is imperative to gain a deeper understanding of the underlying mechanisms driving this association. 



  1. Yu R, Liu X, Deng X, Li S, Wang Y, Zhang Y, et al. Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis. Front Immunol. 2023;14:1211790.  
  1. Hozumi H, Fujisawa T, Enomoto N, Nakashima R, Enomoto Y, Suzuki Y, et al. Clinical Utility of YKL-40 in Polymyositis/dermatomyositis-associated Interstitial Lung Disease. J Rheumatol. 2017 Sep;44(9):1394–401.