Background/Purpose: Idiopathic inflammatory myopathies (IIM) are characterized by inflammatory muscle injury. Circulating cell-free DNA (cfDNA), including nuclear (cfnDNA) and mitochondrial (cfmtDNA) DNA, has been shown to increase after exercise primarily due to apoptosis or necrosis and might be a promising biomarker for inflammatory muscle injury in IIM. The aim was to explore the association between cfnDNA and cfmtDNA and muscle damage, strength, and metabolic function.

Methods: 66 patients with IIM were included: 22 male; mean (SD) age 57.6 (13.9); disease duration 2.3 (3.0) years; 21 dermatomyositis (DM)/ 29 polymyositis (PM), both without statin history/ 16 immune-mediated necrotizing myopathystatin-induced (IMNM). Follow-up at 6 months of immunosuppressive therapy included 15 patients (6 DM, 6 PM, 3 IMNM; disease duration 0.9 (1.3) years). Basal laboratory parameters, disease features, current treatment and comorbidities were recorded. Body composition was examined by bioelectric impedance analysis (BIA-2000-M). cfDNA was isolated using the Plasma/Serum Cell-Free Circulating DNA Purification Mini Kit (Norgen Biotek). qPCR was used to analyze 2 independent markers for cfnDNA (IL6 and CTO), and cfmtDNA (ND5 and CO3). Data are presented as mean (SEM).

Results: There were no significant differences in plasma concentrations of selected cfnDNA and cfmtDNA markers among DM, PM and IMNM (Table 1). Elevated expression of both cfnDNA and cfmtDNA was associated with worse disease damage (MDI), decreased muscle strength (MMT8), higher body fat percentage (BF%), reduced basal metabolic rate (BMR), and decreased capacity for physical activity (higher ECM/BCM and lower phase angle). cfnDNA expression also positively correlated with disease activity (MITAX), while cfmtDNA positively correlated with age and glucose plasma levels (Table 2). The analysis of a 6-month follow-up in 15 IIM patients after immunosuppressive treatment initiation showed statistically significant reductions in disease activity, improvement of muscle strength, and decreases in levels of muscle involvement markers (CK, LD, myoglobin) (p< 0.05 for all) (Table 3). However, the decrease in both cfnDNA and cfmtDNA expression was not significant. Lower baseline expression of cfnDNA (IL6) predicted a trend to an increase in muscle strength (MMT8) (p=0.09).

Conclusion: Expression of nuclear and mitochondrial cfDNA did not vary among the IIM subtypes but was associated with disease activity and damage, muscle weakness, and physical function in patients with IIM. Although there was a significant improvement in muscle impairment (decrease in muscle markers, increase in muscle strength) along with the reduction in glucocorticoid doses observed in only 15 IIM patients after a 6-month initial immunosuppressive therapy, the expression of cfnDNA and cfmtDNA did not change, There was a promising prediction of increased muscle strength by baseline expression of cfnDNA (IL6). Therefore, both cfnDNA and cfmtDNA deserve further studies to elucidate their potential role as a marker of muscle damage, or treatment response in IIM. Acknowledgments: MH CR 023728, NU21-01-00146, NU21-05-00322, BBMRI.cz-LM2023033, SVV 260638

Table 1: Baseline expression of cfnDNA and cfmtDNA in IIM

Table 2: associations of cfDNA and markers of muscle and metabolic involvement in IIM

Table 3: Expression of cfnDNA and cfmtDNA in 15 IIM after 6 months of immunosuppression

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cell-free-dna-as-a-potential-marker-of-muscle-involvement-and-treatment-response-in-myositis/