Performance of serum biomarkers reflective of different pathogenic processes in systemic sclerosis-associated interstitial lung disease.

Györfi AH, Filla T, Dickel N, Möller F, Li YN, Bergmann C, Matei AE, Harrer T, Kunz M, Schett G, Distler JH (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Rheumatology Oxford University Press

Book Volume: 63

Pages Range: 962-969

Journal Issue: 4

DOI: 10.1093/rheumatology/kead332

Abstract

OBJECTIVE: Interstitial lung disease (ILD) is the leading cause of mortality in SSc. Novel biomarkers are crucial to improve outcomes in SSc-ILD. We aimed to compare the performance of potential serum biomarkers of SSc-ILD that reflect different pathogenic processes: KL-6 and SP-D (epithelial injury), CCL18 (type 2 immune response), YKL-40 (endothelial injury and matrix remodelling) and MMP-7 (ECM remodelling). METHODS: Baseline and follow-up serum samples from 225 SSc patients were analysed by ELISA. Progressive ILD was defined according to the 2022-ATS/ERS/JRS/ALAT guidelines. Linear mixed models and random forest models were used for statistical analyses. RESULTS: Serum levels of KL-6 [MD 35.67 (95% CI 22.44-48.89, P < 0.01)], SP-D [81.13 (28.46-133.79, P < 0.01)], CCL18 [17.07 (6.36-27.77, P < 0.01)], YKL-40 [22.81 (7.19-38.44, P < 0.01)] and MMP-7 [2.84 (0.88-4.80, P < 0.01)] were independently associated with the presence of SSc-ILD. A machine-learning model including all candidates classified patients with or without ILD with an accuracy of 85%. The combination of KL-6 and SP-D was associated with the presence [0.77 (0.53-1.00, P' <0.01)] and previous progression of SSc-ILD [OR 1.28 (1.01-1.61, P' =0.047)]. Higher baseline levels of KL-6 [OR 3.70 (1.52-9.03, P < 0.01)] or SP-D [OR 2.00 (1.06-3.78, P = 0.03)] increased the odds of future SSc-ILD progression, independent of other conventional risk factors, and the combination of KL-6 and SP-D [1.109 (0.665-1.554, P < 0.01)] showed improved performance compared with KL-6 and SP-D alone. CONCLUSION: All candidates performed well as diagnostic biomarkers for SSc-ILD. The combination of KL-6 and SP-D might serve as biomarker for the identification of SSc patients at risk of ILD progression.

Authors with CRIS profile

Nicholas Dickel Lehrstuhl für Medizinische Informatik Christina Bergmann Department of Medicine 3 – Rheumatology and Immunology Thomas Harrer Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz Meik Kunz Lehrstuhl für Medizinische Informatik Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Universitätsklinikum Düsseldorf DE Germany (DE)

How to cite

APA:

Györfi, A.H., Filla, T., Dickel, N., Möller, F., Li, Y.N., Bergmann, C.,... Distler, J.H. (2024). Performance of serum biomarkers reflective of different pathogenic processes in systemic sclerosis-associated interstitial lung disease. Rheumatology, 63(4), 962-969. https://doi.org/10.1093/rheumatology/kead332

MLA:

Györfi, Andrea Hermina, et al. "Performance of serum biomarkers reflective of different pathogenic processes in systemic sclerosis-associated interstitial lung disease." Rheumatology 63.4 (2024): 962-969.

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