Rapid Discrimination of Tuberculosis and Sarcoidosis by Next-Generation Sequencing

Background: Tuberculosis (TB) is caused by the infection of Mycobacterium tuberculosis (MTB) and shares highly similar clinical, radiological, and histopathological characteristics with sarcoidosis (SA). Correctly distinguishing SA from TB is still one of the clinical challenges.  Methods: This study enrolled 44 TB patients and 47 SA patients that were clinically diagnosed by chest radiography, pathological examination, routine smear microscopy, and culture. The MTB genome was captured and sequenced directly from tissue specimens by operation or biopsy and evaluated the feasibility of next-generation sequencing (NGS) for the MTB genome in the differential diagnosis of TB from SA. Findings: Following the depth > 10× and coverage > 15% filter of the sequencing data, TB patients were well identified by the NGS approach directly in using of operation or biopsy specimens without clinical pretreatment. The sensitivity, specificity, and concordance of NGS diagnostic method was 81.8% (36/44), 95.7% (45/47) and 89.0% (81/91), respectively (Kappa value = 0.78, 95%CI = 0.65-0.91 P-value = 0.00).  Interpretation: Our study established an improved method of rapid strategy in distinguishing patients with TB, and have a potential benefit in clinical implications. Funding Statement: This work was supported by the Shanghai Science and Technology SMEs Technology Innovation Fund (1702H117500), the Jiaxing Leading Talent Entrepreneurship Project, and the Technology innovation projects of Jiaxing. Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: This study was conducted according to the principles of the World Medical Association Declaration of Helsinki. The study was approved specifically by the Internal Review Board of the Affiliated Zhongshan Hospital, Fudan University. All participants were informed and consent to participate in this retrospective study (IRB approval No. B2017-122).