A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 75; no. 8; pp. 1424 - 1433
• Main Authors: Jee, Adelle S., Stewart, Iain, Youssef, Peter, Adelstein, Stephen, Lai, Donna, Hua, Sheng, Stevens, Wendy, Proudman, Susanna, Ngian, Gene‐Siew, Glaspole, Ian N., Moodley, Yuben P., Bleasel, Jane F., Macansh, Sacha, Nikpour, Mandana, Sahhar, Joanne, Corte, Tamera J., Cooley, Helen M., Hansen, Dylan, Hill, Catherine, Major, Gabor A. C., Moghaddami, Mahin, Nash, Peter, Roddy, Janet, Tymms, Kathleen, Walker, Jennifer G., Cooper, Wendy A., Ellis, Samantha J., Goh, Nicole S. L., Grainge, Christopher, Hopkins, Peter, Keir, Gregory J., Mahar, Annabelle, Reynolds, Paul N., Tan, Dino, Zappala, Chris J., Nguyen, MaiAnh
• Format: Journal Article
• Language: English
• Published: Boston, USA Wiley Periodicals, Inc 01.08.2023; Wiley Subscription Services, Inc
• Subjects: Australia; Biomarkers; Carbon monoxide; Cell adhesion; Cohort analysis; Cohort Studies; Diagnosis; Empirical analysis; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Intercellular Adhesion Molecule-1; Lung; Lung diseases; Lung Diseases, Interstitial - diagnosis; Lung Diseases, Interstitial - etiology; Observational studies; Performance evaluation; Protein D; Pulmonary Surfactant-Associated Protein D; Quality of Life; Radiography; Respiratory function; Scleroderma; Scleroderma, Systemic; Surfactant protein D; Systemic sclerosis; Australia
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.42491

Objective In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD). Methods We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF‐controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc‐ILD, and its association with lung function, disease extent on radiography, and patient health–related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc‐ILD from IPF‐controls were identified. Results A composite biomarker index, comprising surfactant protein D (SP‐D), Ca15‐3, and intercellular adhesion molecule 1 (ICAM‐1), was strongly associated with SSc‐ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59–35.21) (P < 0.001). The composite index strengthened the performance of individual biomarkers for SSc‐ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (for biomarker index score 3 relative to biomarker index score 0, the adjusted absolute change in forced vital capacity percent predicted was −17.84% and the diffusing capacity for carbon monoxide percent predicted was −20.16%; both P < 0.001). Conclusion A composite serum biomarker index, comprising SP‐D, Ca15‐3, and ICAM‐1, may improve the identification and risk stratification of ILD in SSc patients at baseline.