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. 2021 Mar;8(1):517-527.
doi: 10.1007/s40744-021-00288-x. Epub 2021 Feb 14.

Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population

Muhan Zheng  1 , Aiju Lou  2 , Haoru Zhang  1 , Shijie Zhu  3 , Min Yang  4 , Weinan Lai  5
Affiliations

Serum KL-6, CA19-9, CA125 and CEA are Diagnostic Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease in the Chinese Population

Muhan Zheng et al. Rheumatol Ther. 2021 Mar.

Abstract

Introduction: This study aimed to evaluate the role of tumor marker carbohydrate antigen (CA) 125 (CA125), CA19-9, carcinoembryonic antigen (CEA) and Krebs von den Lungen-6 (KL-6) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.

Methods: A retrospective analysis was performed. Fifty RA patients (24 patients with ILD and 26 patients without ILD), 10 healthy subjects and 14 patients with other connective tissue disease-associated interstitial lung disease were included. Serum levels of KL-6 and tumor markers CA19-9, CA125 and CEA were measured. Chest HRCT of patients with ILD was scored quantitatively according to the degree of fibrosis. Data on the C-reactive protein, erythrocyte sedimentation rate, rheumatoid factors and anti-cyclic peptide containing citrulline (anti-CCP) were also collected.

Results: Serum levels of KL-6, CA19-9, CA125 and CEA in the RA-ILD group were significantly higher than those in the RA-no-ILD group. The serum KL-6 level was positively correlated with the HRCT fibrosis score (r = 0.63, p = 0.002). The logistic regression analysis showed that CA19-9 and smoking were associated with RA-ILD [OR = 1.118, 95% CI = (1.038, 1.204), p = 0.003 for CA19-9, OR = 14.969, 95% CI = (1.750, 128.043), p = 0.013 for smoking].

Conclusions: KL-6 level and tumor markers were elevated in RA-ILD, and strongly associated with the severity of ILD, supporting their value as pathogenically relevant biomarkers, which can contribute to noninvasive detection of this extra-articular disease complication.

Keywords: Interstitial lung disease; KL-6; Rheumatoid arthritis; Tumor markers.

Plain language summary

Interstitial lung disease (ILD) is a common pulmonary manifestation of RA associated with high morbidity and mortality. Our retrospective study was performed to investigate the clinical utility of tumor marker carbohydrate antigen (CA) 125 (CA125), CA19-9, carcinoembryonic antigen (CEA) and Krebs von den Lungen-6 (KL-6) in the diagnosis and determining the severity of RA-ILD. Fifty RA patients (24 patients with ILD and 26 patients without ILD), 10 healthy subjects and 14 patients with other connective tissue disease-associated interstitial lung disease (CTD-ILD) were included. The results showed KL-6 level and tumor markers were elevated in RA-ILD, and strongly associated with the severity of ILD, which meant KL-6 and tumor markers might be useful pathogenically relevant biomarkers and could be predictors for the diagnosis and determination of severity of ILD in RA.

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Figures

Fig. 1
Fig. 1
Elevated KL-6 and tumor markers level in RA-ILD patients. The levels of KL-6 (a), CA19-9 (b), CA125 (c) and CEA (d) were significantly higher in RA-ILD patients. RA-no-ILD rheumatoid arthritis-without interstitial lung disease, RA-ILD rheumatoid arthritis-related interstitial lung disease, HC healthy controls, CTD-ILD connective tissue disease-associated interstitial lung disease, KL-6 Krebs von den Lungen-6, CA125 carbohydrate antigen 125, CA19-9 carbohydrate antigen 19-9, CEA carcinoembryonic antigen
Fig. 2
Fig. 2
Predictive capacity of tumor markers and KL-6 in the presence of ILD in RA. KL-6 Krebs von den Lungen-6, CA125 carbohydrate antigen 125, CA19-9 carbohydrate antigen 19-9, CEA carcinoembryonic antigen, RA-ILD rheumatoid arthritis-related interstitial lung disease
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