The correlation between circulating DNA fragments, inflammation, oxidative stress biomarkers, and progressive multiple sclerosis: a case-control study

Cell-free DNA (cfDNA) is increasingly used in clinical diagnostics; however, its role in progressive multiple sclerosis (PMS) remains underexplored. This study aimed to investigate the relationship between cfDNA characteristics and disease status in PMS by analyzing cfDNA concentration and fragment size, along with biomarkers of inflammatory and oxidative stress.

A case-control study was conducted involving 95 PMS patients and 95 matched healthy controls. Based on the 2017 McDonald criteria, PMS patients were further classified into secondary PMS (SPMS, n = 73) and primary PMS (PPMS, n = 22) groups. We measured and compared the levels of cfDNA, inflammatory markers - including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) - and oxidative stress indicators, such as malondialdehyde (MDA), total antioxidant capacity (T-AOC), glutathione (GSH), and catalase (CAT).

Significant differences were observed between PMS patients and controls in cfDNA content, fragment size, inflammatory indices, and oxidative stress markers (all p < 0.001). Furthermore, PPMS patients exhibited higher cfDNA content, greater fragment size, and elevated levels of SII, MDA, and CAT compared to SPMS patients (all p < 0.01). CfDNA content was positively correlated with SII (r = 0.274, p = 0.007), MDA (r = 0.267, p = 0.009), and CAT (r = 0.255, p = 0.013). ROC analysis indicated that both cfDNA content (AUC = 0.781) and fragment size (AUC = 0.712) had diagnostic value for PPMS, and their combination yielded the highest efficacy (AUC = 0.823, p < 0.001).

CfDNA parameters are significantly altered in PMS patients and correlate with inflammatory and oxidative stress markers. These findings suggest that cfDNA could serve as a promising biomarker for the early diagnosis and stratification of PMS.