J Rheum Dis.  2021 Oct;28(4):234-241. 10.4078/jrd.2021.28.4.234.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

• Moon J
• Lee JS
• Yoon YI
• Chang SH
• Lee YA
• Ha YJ
• Kang EH
• Park YB
• Lee H
• Choe JY
• Lee EY
• Study Group, Korean Rheumatoid Arthritis Interstitial Lung Disease (KORAIL)

• KMID: 2520436
• DOI: http://doi.org/10.4078/jrd.2021.28.4.234

Abstract

Objective
The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD.
Methods
We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%).
Results
MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001).
Conclusion
MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Keyword

Rheumatoid arthritis with interstitial lung disease; Matrix metalloproteinase-7; Surfactant protein-D; Krebs von den Lungen-6

Figure

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  Figure 1 Correlations between FVC and DLCO and serum MMP-7, SP-D and KL-6. FVC: forced vital capacity, DLCO: diffusing capacity for carbon monoxide, MMP-7: matrix metallopeptidase 7, SP-D: surfactant protein D, KL-6: Krebs von den Lungen 6.

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  Figure 2 Serum MMP-7, SP-D, and KL-6 levels according to semiquantitative CT grades. MMP-7: matrix metallopeptidase 7, SP-D: surfactant protein D, KL-6: Krebs von den Lungen 6, CT: computed tomography.

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