Aim: Intestinal tuberculosis (ITB) and Crohn's disease (CD) have overlapping clinical, radiographic, endoscopic and histologic features, which makes the distinction between these two disease entities a great challenge in tuberculosis-endemic countries. The aim of the study was to investigate the value of in vitro interferonγ release assay (T-SPOT.TB) in differentiating ITB from CD. Methods: From June 2008 to February 2010, a total of 93 consecutive patients with undetermined ITB or CD were prospectively recruited. Clinical, endoscopic, histologic and therapeutic responses were longitudinally monitored at follow-up evaluation until the final definite diagnosis has been reached. Results: After a median of 6 months' follow-up (interquartile range [IQR], 3.0 to 7.5 months), definitive diagnosis was achieved in 84 of the 93 patients (90%), with 19 having ITB and 65 having CD. On univariate analysis, a long duration of illness, chronic diarrhea, and anemia were significantly more common in CD (P < 0.05). While night sweat, ascites, pulmonary lesions, circumferential ulcer on endoscopy, ileo-cecal valve involvement and epithelioid granulomas were significantly more common in ITB (P < 0.05). On multivariate analysis, T-SPOT.TB (Hazard ratio 7.0, 95% confidence interval [CI] 1.9–25.7) was found to be a good predictor for ITB diagnosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of T-SPOT.TB were 84.2%, 75.4%, 50.0%, and 94.2%, respectively. Conclusions: When differentiating ITB and CD in tuberculosis-endemic regions, T-SPOT.TB blood test may be a helpful and practical diagnostic tool for its high NPV to rule out ITB.

Introduction: Active tuberculosis (ATB), instigated by Mycobacterium tuberculosis (M.tb), rises as a primary instigator of morbidity and mortality within the realm of infectious illnesses. A significant portion of M.tb infections maintain an asymptomatic nature, recognizably termed as latent tuberculosis infections (LTBI). The complexities inherent to its diagnosis significantly hamper the initiatives aimed at its control and eventual eradication.Methodology: Utilizing the Gene Expression Omnibus (GEO), we procured two dedicated microarray datasets, labeled GSE39940 and GSE37250. The technique of weighted correlation network analysis was employed to discern the co-expression modules from the differentially expressed genes derived from the first dataset, GSE39940. Consequently, a pyroptosis-related module was garnered, facilitating the identification of a pyroptosis-related signature (PRS) diagnostic model through the application of a neural network algorithm. With the aid of Single Sample Gene Set Enrichment Analysis (ssGSEA), we further examined the immune cells engaged in the pyroptosis process in the context of active ATB. Lastly, dataset GSE37250 played a crucial role as a validating cohort, aimed at evaluating the diagnostic prowess of our model.Results: In executing the Weighted Gene Co-expression Network Analysis (WGCNA), a total of nine discrete co-expression modules were lucidly elucidated. Module 1 demonstrated a potent correlation with pyroptosis. A predictive diagnostic paradigm comprising three pyroptosis-related signatures, specifically AIM2, CASP8, and NAIP, was devised accordingly. The established PRS model exhibited outstanding accuracy across both cohorts, with the area under the curve (AUC) being respectively articulated as 0.946 and 0.787.Conclusion: The present research succeeded in identifying the pyroptosis-related signature within the pathogenetic framework of ATB. Furthermore, we developed a diagnostic model which exuded a remarkable potential for efficient and accurate diagnosis.

To investigate the clinical features and potential risk factors of active tuberculosis (ATB) in Behçet’s disease (BD), we conducted a case-control study on hospitalized BD patients in our institute from 2010 to 2019. BD patients with ATB were enrolled as the case group. The control group was selected by random number sampling from the remaining BD patients, including those with latent tuberculosis infection, previous tuberculosis, or without tuberculosis. Finally, we reviewed 386 BD patients and identified 21 (5.4%) ATB cases, including four (19.0%) microbiologically confirmed and 17 (81.0%) clinically diagnosed. We found that BD patients with ATB were more prone to have systemic symptoms (fever, night sweating, and unexplained weight loss) and/or symptoms related to the infection site. Multivariate logistic regression analysis revealed that erythrocyte sedimentation rate ESR > 60 mm/h ( OR = 13.710 , 95% CI (1.101, 170.702)), increased IgG ( OR = 1.226 , 95% CI (1.001, 1.502)), and positive T-SPOT.TB ( OR = 7.793 , 95% CI (1.312, 48.464), for 24-200 SFC/106PBMC; OR = 17.705 95% CI (2.503, 125.260), for >200 SFC/106PBMC) were potential risk factors for ATB in BD patients. Our study suggested that when BD patients have systemic symptoms with significantly elevated TB-SPOT, the diagnosis of ATB should be considered.

To investigate the diagnostic value of the interferon-γ release assay (IGRA) for detecting tuberculosis (TB) infection in patients with Behçet’s disease (BD). We retrospective analyzed the data collected from 173 BD patients hospitalized between 2010 and 2015. Ninety-nine healthy volunteers were enrolled as a control group. IGRA was performed using T-SPOT.TB. The diagnosis of active TB (ATB) was based on clinical, radiological, microbiological, histopathological information and the response to anti-TB therapy. Latent TB (LTB) infection was defined as asymptomatic patients with positive T-SPOT.TB. TB infection was documented in 59 BD patients (34.1%). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of T-SPOT.TB for the diagnosis of ATB were 88.9%, 74.8%, 29.1%, 98.3%, 3.53 and 0.15, respectively. The receiver-operating-characteristic curve demonstrated that spot-forming cells (SFCs) of 70/106 PBMC was the optimal cutoff for diagnosing ATB, with an area under the curve of 0.891. Furthermore, the median SFCs in ATB group was significantly higher than those in LTB infection (466/106 PBMC vs. 68/106 PBMC, p = 0.007) or previous TB infection (466/106 PBMC vs. 96/106 PBMC, p = 0.018). A significant discrepancy between T-SPOT.TB and tuberculin skin test was noted (kappa coefficient = 0.391, p = 0.002). T-SPOT.TB, an IGRA, may assist in the diagnosis of ATB in BD patients, and the higher SFCs suggest ATB in BD patients.

Patients with rheumatic disease (RD) are particularly vulnerable to progressing to tuberculosis disease (TBD). The effectiveness of tuberculosis preventive treatment (TPT) in this high risk group needs systematic assessment. We conducted a systematic review and meta-analysis by searching PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and China National Knowledge Internet (CNKI) for relevant cohort studies from inception through January 2025. Eligible studies evaluated the incidence of TBD and/or the effectiveness of TPT in patients with RD. Two authors independently reviewed and extracted summary data from published reports. Pooled incidence rate (IR), risk ratio (RR) and their 95% confidence interval (CI) were calculated as the primary effect measure. Prospero registration number is CRD42023473966. 64 studies with 116,015 patients with RD were included to evaluate effectiveness of TPT. TPT decreased the overall risk of TBD in patients with RD (RR: 0.76, 95% CI 0.63-0.91). TPT showed better effectiveness in high tuberculosis (TB) burden countries/regions (RR: 0.46, 95% CI 0.27-0.77). Using isoniazid (INH) monotherapy for 9-12 months was effective (RR: 0.54, 95% CI 0.35-0.85). Taking tuberculin skin test (TST) combined with interferon gamma release assays (IGRA) as tuberculosis infection (TBI) screening methods might maximize the benefits of TPT (RR: 0.58, 95% CI 0.39-0.88). TPT showed optimal protective effects in patients with RD in TBI positive status (RR: 0.11, 95% CI 0.04-0.32). Compared with patients with RD receiving biologics, TPT showed better effects in patients with RD only receiving traditional treatment (RR: 0.44, 95% CI 0.27-0.73). And TPT performed more effectively in systematic lupus erythematosus (SLE) than arthritis. TPT decreased the risk of TBD in patients with RD, especially in TB high burden countries/regions. When using isoniazid monotherapy, extending the treatment course might have better protection. TST combined with IGRA might be optimal when screening the TBI. More types of RDs, short-course regimens containing rifamycins and high-quality randomized controlled trials (RCT) should be the focus of future research. This study was supported by the National Natural Science Foundation of China (82373648), Capital's Funds for Health Improvement and Research (2024-2-4016), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-C-013, 2022-PUMCH-A-119).

Background The differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging in clinical practice. We aimed to evaluate the diagnostic accuracy of the IFN-gamma/TNF-alpha FluoroSpot assay for differentiating ATB from LTBI. Methods We conducted a pilot study of case-control design, using the FluoroSpot assay to simultaneously detect IFN-gamma and TNF-alpha secretion at the single-cell level. The frequencies of antigen-specific single TNF-alpha-, total TNF-alpha-, single IFN-gamma-, total IFN-gamma- and dual IFN-gamma/TNF-alpha-secreting T cells were detected. The optimal cutoffs value of frequencies for differentiating ATB from LTBI were determined according to receiver operating characteristic curve analysis. The sensitivity, specificity, predictive values (PV) and likelihood ratios (LR) of the FluoroSpot assay were calculated. Results Thirty patients diagnosed microbiologically with ATB, 36 healthcare workers with LTBI and 36 healthy controls were enrolled. After stimulated by ESAT-6 or CFP-10 peptides, the median frequencies of single TNF-alpha-, total TNF-alpha-, single IFN-gamma-, total IFN-gamma- and dual IFN-gamma/TNF-alpha-secreting T cells in ATB patients were all significantly higher than those in LTBI and HC groups (P < 0.01). The frequencies of total IFN-gamma-secreting T cells detected by FluoroSpot assay correlated significantly with those of T-SPOT.TB (r = 0.910 for ESAT-6, P < 0.001, r = 0.845 for CFP-10, P < 0.001). After stimulated by ESAT-6 peptides, with total TNF-alpha-secreting T cells frequencies at a cut off value of 21 iSFCs/250,000 PBMCs, the sensitivity, specificity, PLR, NLR, PPV, NPV of IFN-gamma/TNF-alpha FluoroSpot assay in differentiating ATB from LTBI were 96.7% (95%CI, 82.8-99.9%), 94.3% (95%CI, 80.8-99.3%), 16.92 (95%CI, 4.40-65.08), 0.04 (95%CI, 0.01-0.24), 93.6% (95%CI,78.6-99.2%) and 97.1% (95%CI, 84.7-99.9%), respectively. With the frequencies of total TNF-alpha- and total IFN-gamma-secreting T cells stimulated by ESAT-6 peptides combined, the specificity was increased to 97.1%, and the positive likelihood ratio to 31.5. The combination with CFP-10 might not improve the diagnostic accuracy of the ESAT-6 for differentiating ATB from LTBI. Conclusions IFN-gamma/TNF-alpha FluoroSpot assay might have potential to help differentiate ATB from LTBI, but the findings need to be further verified by cross-sectional or prospective cohort studies.