Rapid discrimination between tuberculosis and sarcoidosis using next-generation sequencing.

Abstract Objectives Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) and shares its clinical, radiological, and histopathological characteristics with sarcoidosis (SA). Accurately distinguishing SA from TB remains a clinical challenge. Methods In this study, we enrolled 44 TB and 47 SA patients clinically diagnosed using chest radiography, pathological examination, routine smear microscopy, and microbial culture. The MTB genome was captured and sequenced directly from tissue specimens obtained upon operation or biopsy, and the feasibility of next-generation sequencing (NGS) for the MTB genome in the differential diagnosis of TB from SA was evaluated. Results Using a depth > 10× and coverage > 15% of the sequencing data, TB patients were identified via the NGS approach directly using operation or biopsy specimens without clinical pretreatment. The sensitivity, specificity, and concordance of the NGS method were 81.8% (36/44), 95.7% (45/47), and 89.0% (81/91), respectively (kappa value = 0.78, 95% confidence interval = 0.65–0.91, P-value = 0.00). Conclusions Our study established an improved NGS strategy for rapidly distinguishing patients with TB from those with SA and has potential clinical benefits.