Objective Interstitial lung disease (ILD) is a severe extraglandular complication of primary Sjögren's syndrome (pSS) that significantly impacts prognosis, yet non-invasive diagnostic tools remain limited in rheumatology practice. This study aimed to evaluate the association between serum growth differentiation factor 15 (GDF-15) and prevalent pSS-associated ILD (pSS-ILD), and to develop an exploratory diagnostic classification model for identifying pSS-ILD. Methods In this cross-sectional study, 60 pSS patients (22 with ILD confirmed by high-resolution computed tomography [HRCT] and Warrick score, 38 without ILD) and 20 healthy controls were enrolled. Serum GDF-15 levels were measured by ELISA. Clinical data, including disease activity, laboratory parameters, and pulmonary function tests (FVC, DLCO), were systematically collected. An exploratory diagnostic classification model was developed using LASSO regression and evaluated by ROC analysis. Results Serum GDF-15 was significantly elevated in pSS-ILD patients compared to those without ILD and healthy controls (median 1294.1 vs. 664.33 vs. 442.93 pg/mL, both P < 0.001). In pSS-ILD patients, GDF-15 positively correlated with radiological severity (Warrick score, r = 0.465, P = 0.034) and negatively correlated with pulmonary function parameters, including FVC% (r = -0.629, P = 0.028) and DLCO% (r = -0.616, P = 0.033). LASSO regression identified GDF-15, age, lactate dehydrogenase, and IgG as key predictors. The combined model showed high apparent diagnostic performance for identifying prevalent pSS-ILD (AUC = 0.925, 95% CI: 0.850–1.000), outperforming individual clinical parameters. Conclusion Serum GDF-15 is a promising biomarker candidate associated with pSS-ILD, reflecting both radiological severity and pulmonary function impairment. Integration of GDF-15 with routine clinical variables may provide a practical, non-invasive approach for identifying pSS patients with prevalent ILD, although prospective and externally validated studies are required before clinical implementation. However, the model should be regarded as exploratory and may be unstable because of the limited sample size, the low event-per-variable ratio, and the baseline age imbalance between groups; prospective, age-balanced, and externally validated studies are required before clinical implementation. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key points • Serum GDF-15 is significantly elevated in primary Sjögren's syndrome patients with interstitial lung disease and correlates with both radiological severity and pulmonary function impairment. • A multivariable exploratory diagnostic model combining GDF-15 with age, lactate dehydrogenase, and IgG showed high apparent diagnostic performance for identifying prevalent pSS-ILD. • This model may help identify pSS patients with concurrent ILD who warrant further pulmonary evaluation, but its stability should be verified in larger age-balanced cohorts with prospective external validation. </entry> </row> </tbody> </tgroup> </Table>

Serum growth differentiation factor 15 as a candidate biomarker associated with interstitial lung disease in primary Sjögren’s syndrome: a clinical cross-sectional study

期刊论文
发表日期：

2026年7月14日

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Meilu Liu,
Yashuang Su,
Liu Yang,
He Xue,
Shaoying Guo,
Nannan Niu,
Jingjing Li,
Dongtai Li,
Zhidong Zhang,
Zigui Yang,
Ning Liu,
Fengxiao Zhang,
Wei Lin

摘要

Objective

Interstitial lung disease (ILD) is a severe extraglandular complication of primary Sjögren's syndrome (pSS) that significantly impacts prognosis, yet non-invasive diagnostic tools remain limited in rheumatology practice. This study aimed to evaluate the association between serum growth differentiation factor 15 (GDF-15) and prevalent pSS-associated ILD (pSS-ILD), and to develop an exploratory diagnostic classification model for identifying pSS-ILD.

Methods

In this cross-sectional study, 60 pSS patients (22 with ILD confirmed by high-resolution computed tomography [HRCT] and Warrick score, 38 without ILD) and 20 healthy controls were enrolled. Serum GDF-15 levels were measured by ELISA. Clinical data, including disease activity, laboratory parameters, and pulmonary function tests (FVC, DLCO), were systematically collected. An exploratory diagnostic classification model was developed using LASSO regression and evaluated by ROC analysis.

Results

Serum GDF-15 was significantly elevated in pSS-ILD patients compared to those without ILD and healthy controls (median 1294.1 vs. 664.33 vs. 442.93 pg/mL, both P < 0.001). In pSS-ILD patients, GDF-15 positively correlated with radiological severity (Warrick score, r = 0.465, P = 0.034) and negatively correlated with pulmonary function parameters, including FVC% (r = -0.629, P = 0.028) and DLCO% (r = -0.616, P = 0.033). LASSO regression identified GDF-15, age, lactate dehydrogenase, and IgG as key predictors. The combined model showed high apparent diagnostic performance for identifying prevalent pSS-ILD (AUC = 0.925, 95% CI: 0.850–1.000), outperforming individual clinical parameters.

Conclusion

Serum GDF-15 is a promising biomarker candidate associated with pSS-ILD, reflecting both radiological severity and pulmonary function impairment. Integration of GDF-15 with routine clinical variables may provide a practical, non-invasive approach for identifying pSS patients with prevalent ILD, although prospective and externally validated studies are required before clinical implementation. However, the model should be regarded as exploratory and may be unstable because of the limited sample size, the low event-per-variable ratio, and the baseline age imbalance between groups; prospective, age-balanced, and externally validated studies are required before clinical implementation.

Key points

• Serum GDF-15 is significantly elevated in primary Sjögren's syndrome patients with interstitial lung disease and correlates with both radiological severity and pulmonary function impairment.

• A multivariable exploratory diagnostic model combining GDF-15 with age, lactate dehydrogenase, and IgG showed high apparent diagnostic performance for identifying prevalent pSS-ILD.

• This model may help identify pSS patients with concurrent ILD who warrant further pulmonary evaluation, but its stability should be verified in larger age-balanced cohorts with prospective external validation.