Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis

Kwon, Ji‐Soo; Park, Joung Ha; Kim, Ji Yeun; Hee, Hye; Kim, Minjae; Chong, Yong Pil; Lee, Sang‐Oh; Choi, Sang‐Ho; Kim, Yang Soo; Woo, Jun Hee; Koo, Yong Seo; Jeon, Sang-Beom; Lee, Sang‐Ahm; Kim, Sung-Han

doi:10.4269/ajtmh.18-0947

Cited by 15 publications

(17 citation statements)

References 57 publications

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“…Besides, the lack of accessible and timely methods also contributed to a delay in diagnosis and subsequent morbidity and mortality for TBM patients, particularly those in resource-limited settings ( 29 ). Although the potential biomarkers of proteome ( 30 ), metabolome ( 31 ), and transcriptome ( 32 ) have been identified for TBM diagnosis in recent years, these markers have not been sufficiently verified. In this study, we compared the laboratory features including CSF indexes and TBAg/PHA ratio in T-SPOT assay among patients with these two types of meningitis.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Model for Discrimination Between Tuberculous Meningitis and Bacterial Meningitis

et al. 2021

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BackgroundThe differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM.MethodsPatients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model.ResultsA total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840–0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%–77.77%) and a specificity of 92.86% (95% CI, 85.98%–96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921–0.978), with 81.58% (95% CI, 71.42%–88.70%) sensitivity and 91.84% (95% CI, 84.71%–95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867–0.980) with 79.49% (95% CI, 64.47%–89.22%) sensitivity and 90.91% (95% CI, 81.55%–95.77%) specificity.ConclusionsThe diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Model for Discrimination Between Tuberculous Meningitis and Bacterial Meningitis

et al. 2021

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“…In other studies with TB pleural effusion patients, CCL27 levels were significantly higher in PE samples from anergic patients with TPE, compared to those in non-anergic TPE and malignant PE (p < 0.001) (55). Furthermore, recent studies for the suspected cases of tuberculous meningitis (TBM) showed that the upregulated cytokine/chemokine profiles including IL-12p40, IL-13, and MIP-1α as potentially useful adjunctive markers for diagnosis of TBM (56). These data suggest that specific chemokine levels, combined with the known biomarker ADA levels, might be helpful for the diagnosis of extrapulmonary TB.…”

Section: Biomarkers During Extrapulmonary Tb Infectionmentioning

confidence: 94%

The Roles of Chemokines in Immune Response to Mycobacterial Infection

Paik

Yang

Suh

et al. 2020

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Tuberculosis (TB), a global and deadly infectious disease caused by Mycobacterium tuberculosis (Mtb), is manifested with host immune reaction. The balanced regulation between protective immune and pathologic inflammatory responses is critical to control progression to TB. Chemokines are a large family of cytokines that play an essential role for chemotaxis of immune and inflammatory cells to the sites of infection. Numerous chemokines including CXCL10 were reported as potential biomarkers of various stages of TB infection. In addition, several chemokines and their receptors play as key players to coordinate host immune defense as innate effectors and mediators of adaptive immune responses. Accumulating evidence suggests that some chemokines, if uncontrolled, are associated with host pathological inflammation during infection. In this review, we will discuss recent advances in understanding which chemokines have potentials as diagnostic markers. In addition, we focus the roles and mechanisms by which chemokines and their receptors are involved in both host immune protection and pathology during TB infection. The controlled activation of chemokine system will determine the coordinated biological outcomes of innate immune responses during pathogenic infection.

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“…After independent reviews, 27 studies met the inclusion criteria and were finally included into meta-analysis ( Table 1 and Figure 1 ). The PB-based T-SPOT was performed in 25 studies ( 26 – 35 , 37 – 42 , 44 – 52 ), and the CSF-based T-SPOT was used in 16 studies ( 26 – 29 , 31 , 32 , 36 – 39 , 41 , 43 , 46 , 48 , 50 , 51 ). Head-to-head comparisons of the diagnostic accuracies of PB T-SPOT against CSF T-SPOT were found in 14 studies.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic Accuracy of T-SPOT.TB Assay for Tuberculous Meningitis: An Updated Meta-Analysis

et al. 2020

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Background: The role of T-SPOT.TB (T-SPOT) assay for tuberculous meningitis (TBM) diagnosis has not been fully assessed. Here, we conducted an updated meta-analysis to evaluate the diagnostic accuracy of peripheral blood (PB) T-SPOT and cerebrospinal fluid (CSF) T-SPOT for diagnosing TBM. Methods: Relevant studies in the PubMed database, EmBase database, Cochrane database, Scopus database, Google Scholar, China National Knowledge Internet, and Wan-Fang database were retrieved from August 1, 2005, to June 22, 2020. Statistical analysis was performed using Stata, Revman, and Meta-Disc software. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curves, and the area under the curve were determined and analyzed. Results: A total of 27 studies were eligible for inclusion within the meta-analysis. The pooled sensitivity and specificity of PB T-SPOT for TBM diagnosis were 0.78 (95% CI, 0.76-0.81) and 0.68 (95% CI, 0.66-0.71), respectively, whereas the pooled PLR, NLR, and DOR were 2.80 (95% CI, 2.29-3.42), 0.32 (95% CI, 0.27-0.38), and 10.08 (95% CI, 7.21-14.08), respectively. On the other hand, the pooled sensitivity and specificity of CSF T-SPOT on diagnosing TBM were 0.76 (95% CI, 0.72-0.80) and 0.88 (95% CI, 0.85-0.90), respectively, whereas the pooled PLR, NLR, and DOR were 5.92 (95% CI, 4.25-8.25), 0.28 (95% CI, 0.21-0.39), and 29.05 (95% CI, 16.40-51.45), respectively. The area under the summary receiver operating characteristic curve values of PB T-SPOT and CSF T-SPOT for TBM diagnosis were 0.83 (95% CI, 0.80-0.86) and 0.92 (95% CI, 0.89-0.94), respectively. Conclusions: CSF T-SPOT showed a higher specificity compared with PB T-SPOT for diagnosing TBM. Both two T-SPOT assays have considerable potential in improving the diagnosis of TBM. Furthermore, the standardization of the operating procedure is further needed when performing CSF T-SPOT.

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Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis

Cited by 15 publications

References 57 publications

Diagnostic Model for Discrimination Between Tuberculous Meningitis and Bacterial Meningitis

Diagnostic Model for Discrimination Between Tuberculous Meningitis and Bacterial Meningitis

The Roles of Chemokines in Immune Response to Mycobacterial Infection

Diagnostic Accuracy of T-SPOT.TB Assay for Tuberculous Meningitis: An Updated Meta-Analysis

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