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Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is one of the primary causes of death worldwide. Rapid and accurate diagnosis of TB is one of the most direct means to reduce the incidence of TB. In this study, urinary proteomic profiling of TB patients and non‐TB individual controls (HCs) was performed, and differentially expressed urinary proteins between TB and HCs were compared and exclusively expressed proteins in TB patients were selected to establish a clinically useful disease marker panel. In total, these top 11 targeted proteins with 265 peptides were scheduled for multiple reaction monitoring validation analysis by using urine samples from 52 TB patients and 52 HCs. The result demonstrated that a three‐protein combination out of the five‐protein panel (namely P22352, Q9P121, P15151, Q13291, and Q8NDA2) exhibited sensitivity rate of 82.7% in the diagnosis of TB. Furthermore, the three‐protein combination could differentiate TB from the latent tuberculosis (LTB) effectively, which exhibited specificity rate of 92.3% for the diagnosis of TB from the LTB category. Although more numbers of clinical samples are required for further verification, the results provided preliminary evidence that this "three‐protein combination" out of the five‐protein panel could probably be a novel TB diagnostic biomarker in clinical application. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is the leading infectious cause of mortality worldwide, especially in developing countries. However, effective means for TB diagnosis, especially for bacillus-negative (Bn) TB laboratory diagnosis, are urgently needed. In the present study, serum IgG from each tuberculosis patients and healthy controls was purified using affinity chromatography. The samples were then analyzed using mass spectrometry (MS) and ultraperformance liquid chromatography (UPLC) methods. We quantitatively assessed the changes of serum IgG galactosylation in 567 human serum samples including 377 pulmonary TB patients and 190 healthy donors (HDs). We found significantly more agalactosylated (G0) vs monogalactosylated (G1) and digalactosylated (G2) N -glycans of IgG in TB patients, including smear-negative TB patients, than in HDs. The detection rate of TB diagnostic performance by MS for IgG–Gal ratio G0/(G1 + G2 × 2) is 90.48% for bacillus-positive (Bp) and 73.16% for Bn TB patients. Further, combination of MS method with other routine laboratory TB diagnostic methods significantly increased the detection rate to 91.01%–98.39%. Similar results were observed in Mycobacterium tuberculosis (M. tb) infection mouse models. The decrease in galactosylation of IgG in TB patients was also qualitatively confirmed using specific lectin blot assay. Using the above techniques, we can discriminate the content of IgG G0 with terminal N -acetylglucosamine and IgG–Gal ratio G0/(G1 + G2 × 2) between TB patients and HDs. Our data suggest that quantitative analysis of serum-based IgG–Gal ratio G0/(G1 + G2 × 2) could be used for TB auxiliary diagnosis with high effectiveness and feasibility and its combination with other routine laboratory TB diagnostic methods could remarkably improve the detection rate. [ABSTRACT FROM AUTHOR]

Abstract Diagnosis of cervical tuberculous lymphadenitis (CTL), the most commonly occurring form of extrapulmonary tuberculosis, remains as a challenge in clinic. Detection of the presence of Mycobacterium tuberculosis (Mtb) in fine needle aspiration cytology (FNAC) samples is one golden criterion to confirm the CTL diagnosis. Due to the non-specific clinical presentation, CTL might be confused with other lymph node enlargement diseases; therefore empirical treatment with non-anti-TB antibiotics is often initially administered. However, it is still unclear whether this diagnostic antibiotic treatment affects the positivity of Mtb detection in FNAC. The demographics and clinical characteristics of 732 lymph node enlargement patients who had underwent FNAC were retrospectively analyzed and 605 (82.65%) of them were diagnosed as CTL. A total of 279 CTL cases (279/605, 46.11%) with completion of three Mtb tests (AFB, NAAT, and Mtb culture) in FNAC samples were selected for analyzing the effect of empirical antibiotic treatment on the positivity of Mtb tests. Compared to CTL patients without antibiotic treatment prior to FNAC, patients received empirical non anti-TB treatment had significantly lower positivity for acid fast bacilli staining (adjusted OR 0.11, 95% CI 0.06–0.21), nucleic acid amplification test (NAAT) (adjusted OR 0.38, 95% CI 0.21–0.71), and Mtb culture (adjusted OR 0.11, 95% CI 0.06–0.19). In conclusion, this study demonstrated that empirical non anti-TB antibiotic treatment reduced the opportunity to confirm CTL by microbiological analysis. Patients with cervical lymph node enlargement should undergo FNAC for Mtb tests prior to initiation of empirical non anti-TB treatment. Highlights • CTL accounted for the most cases of cervical lymph node enlargement. • CTL patients with typical tuberculous cytopathology tended to be found with higher positivity of Mtb in molecular and culture methods. • Empirical non-anti-TB antibiotic treatment reduced the opportunity to confirm CTL by microbiological analysis. [ABSTRACT FROM AUTHOR]

Abstract: Although it has been recognized that ectopic follicle-like B cell aggregate formation is common in the lungs of patients with tuberculosis, the role of infiltrated B cells in human tuberculosis remains to be elucidated. In the present study, we showed that ectopic B cell aggregate formation was associated with containment of Mycobacterium tuberculosis. The area ratio of ectopic B cell aggregates was correlated with localized IL-17 mRNA expression and peripheral TGF-β and IL-6 mRNA expression. Depletion of B cells from pleural fluid mononuclear cells resulted in significantly diminished M. tuberculosis antigen-specific IL-17 and IL-22 production, but not in IFN-γ secretion. Therefore, ectopic lung B cell formation is important for containment of M. tuberculosis, and up-regulation of IL-17 and IL-22 responses may be an important mechanism underlying the protective role B cells in human tuberculosis. [Copyright &y& Elsevier]