Diagnostic accuracy of T-SPOT.TB and TST in detecting active tuberculosis in patients with rheumatic immune diseases: a fully matched comparative study.

BACKGROUND AND OBJECTIVES: Patients with rheumatic immune diseases (RD) are considered a high-risk population for developing active tuberculosis (ATB). Timely and accurate diagnosis of ATB in RD patients is critical for optimizing treatment outcomes and improving prognosis. Both interferon-gamma release assays (IGRA) and the tuberculin skin test (TST) are immunological methods employed in the diagnosis of tuberculosis. However, the diagnostic accuracy of these tests in RD patients, who often experience immune dysfunction, remains underexplored. This study aims to compare the diagnostic accuracy of TST and T-SPOT.TB in RD patients with suspected tuberculosis symptoms.

METHODS: This prospective study included RD patients presenting with any of the following symptoms-fever, cough, night sweats, or unexplained weight loss (all symptoms recommended by the World Health Organization for tuberculosis screening)-from September 2014 to September 2015. Both T-SPOT.TB and TST were performed, and patients were categorized into ATB and non-ATB groups based on clinical diagnosis (including microbiologically confirmed and clinically diagnosed cases). Receiver operating characteristic (ROC) curves were constructed to compare the diagnostic accuracy of T-SPOT.TB and TST for ATB and to determine the optimal cutoff values. Sensitivity, specificity, predictive values, and likelihood ratios were calculated, along with 95% confidence intervals (CIs). The concordance between T-SPOT.TB and TST in diagnosing ATB was also evaluated.

RESULTS: A total of 300 RD patients were enrolled in the study. Of these, 35 (11.7%) were diagnosed with ATB, 258 (86.0%) were excluded from ATB, and 7 (2.3%) had an unclear diagnosis. Among the RD patients, the ATB group exhibited significantly higher frequencies of night sweats (34.3% vs. 14.0%, p=0.002) and unexplained weight loss (17.1% vs. 3.1%, p<0.001) compared to the non-ATB group, while no significant differences were observed between the groups for fever and cough. The area under the ROC curve (AUROC) for T-SPOT.TB was 0.89 (95% CI 0.82-0.95), while the AUROC for TST was 0.74 (95% CI 0.63-0.84), with T-SPOT.TB demonstrating significantly superior diagnostic accuracy (AUROC difference 0.15, 95% CI 0.06-0.24, p=0.001) (Figure). The optimal cutoff for T-SPOT.TB in diagnosing ATB was 24 spot-forming cells (SFCs) per 10^6 peripheral blood mononuclear cells (PBMCs), with sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of 88.6%, 84.9%, 5.86, 0.13, 44.3%, and 98.2%, respectively. The optimal cutoff for TST was a 5mm induration diameter, yielding diagnostic metrics of 57.1%, 88.8%, 5.08, 0.48, 40.8%, and 93.9%, respectively. The sensitivity of T-SPOT.TB was significantly higher than that of TST (p=0.003), while no significant difference in specificity was observed (p=0.193). As the T-SPOT.TB spot count and TST induration diameter increased, the likelihood ratios for diagnosing ATB also increased. The agreement between T-SPOT.TB and TST in diagnosing ATB in RD patients was moderate (kappa=0.466, p<0.001), and parallel testing with TST did not improve the sensitivity of T-SPOT.TB.

CONCLUSION: In RD patients with suspected ATB symptoms, both T-SPOT.TB and TST offer valuable diagnostic assistance. T-SPOT.TB demonstrates superior diagnostic accuracy, particularly in terms of sensitivity. Higher spot counts on T-SPOT.TB or larger induration diameters on TST should raise clinical suspicion for the presence of concurrent ATB.