Global cell-free DNA methylation in patients with active tuberculosis and tuberculosis contacts with latent tuberculosis infection

Abstract

Introduction

To investigate whether the methylation of circulating cell-free DNA (cfDNA) differentiates active tuberculosis (TB) from latent TB infection (LTBI).

Methods

Patients with pulmonary TB, contacts with LTBI, and healthy controls were enrolled (2018–2021). Plasma cfDNA was extracted, and using a 5-methylcytosine (5mC) DNA ELISA kit, the global methylation of cfDNA (5mC-cfDNA) was measured.

Results

59 TB, 63 LTBI, 39 healthy controls were included. The 5mC-cfDNA level was higher in TB (6.4 %) than LTBI (4.1 %) and healthy controls (4.9 %) (both p<0.05). Independent TB factors were 5mC-cfDNA ≥6.6 % and CRP ≥0.32 mg/dL (adjusted odds ratio (aOR) 4.594 [95 % CI:1.628–12.965], p=0.004 and 5.338 [1.659–17.176], p=0.005). Having one or both factors increased TB odds 8- and 16-fold (aOR 8.688 [3.229–23.378], p <0.001 and 16.080 [3.092–83.632], p =0.001).

Conclusion

The global cfDNA methylation level was higher in TB than contacts without TB and helped differentiate patients with TB from contacts with LTBI.