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. 2025 May;19(9):349-355.
doi: 10.1080/17520363.2025.2485014. Epub 2025 Apr 1.

PRDX-4: a novel biomarker similar to KL-6 for predicting the occurrence and progression of systemic sclerosis-ILD

Gizem Tuğçe Alp  1 , İbrahim Vasi  2 , Emre Alp  3 , Aslıhan Avanoğlu Güler  2 , Hazan Karadeniz  2 , Özlem Gülbahar  4 , Abdulsamet Erden  2 , Abdurrahman Tufan  2 , Mehmet Akif Öztürk  2 , Berna Göker  2 , Şeminur Haznedaroğlu  2 , Hamit Küçük  2
Affiliations

PRDX-4: a novel biomarker similar to KL-6 for predicting the occurrence and progression of systemic sclerosis-ILD

Gizem Tuğçe Alp et al. Biomark Med. 2025 May.

Abstract

Aim: Lungs are among the most affected organs in systemic sclerosis (SSc), with interstitial lung disease (ILD) being a leading cause of mortality. Biomarkers are increasingly explored for predicting SSc-ILD detection and progression. This study evaluates the roles of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and peroxiredoxin-4 (PRDX-4) in diagnosing SSc-ILD and monitoring progression.

Methods: A total of 89 individuals (61 SSc patients and 28 healthy volunteers) were included. SSc patients were grouped based on pulmonary function tests and high-resolution computed tomography findings to determine SSc-ILD presence. Patients with SSc-ILD were further categorized by progressive pulmonary fibrosis (PPF) presence based on 2022 guidelines. Serum KL-6, SP-D, and PRDX-4 levels were measured using the Enzyme-Linked Immuno-Sorbent Assay method.

Results: Of the 61 SSc patients, 34 (55.7%) had ILD. Serum KL-6 and PRDX-4 levels were significantly higher in SSc-ILD patients (p = 0.004 and p = 0.012, respectively). KL-6, SP-D, and PRDX-4 levels were elevated in the PPF group compared to stable disease (p = 0.001). PRDX-4 showed the highest diagnostic performance for PPF (AUC: 0.936, sensitivity: 85.7%, specificity: 85%).

Conclusion: KL-6 is a well-established biomarker for SSc-ILD, but PRDX-4 offers superior diagnostic accuracy, especially in identifying PPF.

Keywords: KL-6; PRDX-4; SP-D; Systemic sclerosis; biomarkers; interstitial lung disease.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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