Combination of HLA-DR on -Specific Cells and Tuberculosis Antigen/Phytohemagglutinin Ratio for Discriminating Active Tuberculosis From Latent Tuberculosis Infection

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Dec 3

PMID 34858413

Citations 6

Authors

Ying Luo

Ying Xue

Guoxing Tang

Qun Lin

Huijuan Song

Wei Liu

Botao Yin

Jin Huang

Wei Wei

Liyan Mao

Feng Wang

Ziyong Sun

Affiliations

Soon will be listed here.

Abstract

Background: Novel approaches for tuberculosis (TB) diagnosis, especially for distinguishing active TB (ATB) from latent TB infection (LTBI), are urgently warranted. The present study aims to determine whether the combination of HLA-DR on (MTB)-specific cells and TB antigen/phytohemagglutinin (TBAg/PHA) ratio could facilitate MTB infection status discrimination.

Methods: Between June 2020 and June 2021, participants with ATB and LTBI were recruited from Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort), respectively. The detection of HLA-DR on MTB-specific cells upon TB antigen stimulation and T-SPOT assay were simultaneously performed on all subjects.

Results: A total of 116 (54 ATB and 62 LTBI) and another 84 (43 ATB and 41 LTBI) cases were respectively enrolled from Qiaokou cohort and Caidian cohort. Both HLA-DR on IFN-γTNF-α cells and TBAg/PHA ratio showed discriminatory value in distinguishing between ATB and LTBI. Receiver operator characteristic (ROC) curve analysis showed that HLA-DR on IFN-γTNF-α cells produced an area under the ROC curve (AUC) of 0.886. Besides, TBAg/PHA ratio yield an AUC of 0.736. Furthermore, the combination of these two indicators resulted in the accurate discrimination with an AUC of 0.937. When the threshold was set as 0.36, the diagnostic model could differentiate ATB from LTBI with a sensitivity of 92.00% and a specificity of 81.82%. The performance obtained in Qiaokou cohort was further validated in Caidian cohort.

Conclusions: The combination of HLA-DR on MTB-specific cells and TBAg/PHA ratio could serve as a robust tool to determine TB disease states.

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References

Sivakumaran D, Ritz C, Gjoen J, Vaz M, Selvam S, Ottenhoff T . Host Blood RNA Transcript and Protein Signatures for Sputum-Independent Diagnostics of Tuberculosis in Adults. Front Immunol. 2021; 11:626049. PMC: 7891042. DOI: 10.3389/fimmu.2020.626049. View

Garay-Baquero D, White C, Walker N, Tebruegge M, Schiff H, Ugarte-Gil C . Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis. JCI Insight. 2020; 5(18). PMC: 7526553. DOI: 10.1172/jci.insight.137427. View

Luo Y, Xue Y, Cai Y, Lin Q, Tang G, Song H . Lymphocyte Non-Specific Function Detection Facilitating the Stratification of Infection. Front Immunol. 2021; 12:641378. PMC: 8092189. DOI: 10.3389/fimmu.2021.641378. View

Mpande C, Musvosvi M, Rozot V, Mosito B, Reid T, Schreuder C . Antigen-Specific T-Cell Activation Distinguishes between Recent and Remote Tuberculosis Infection. Am J Respir Crit Care Med. 2021; 203(12):1556-1565. PMC: 8483229. DOI: 10.1164/rccm.202007-2686OC. View

Liao C, Lai C, Tan C, Chou C, Hsu H, Tasi T . False-negative results by enzyme-linked immunospot assay for interferon-gamma among patients with culture-confirmed tuberculosis. J Infect. 2009; 59(6):421-3. DOI: 10.1016/j.jinf.2009.09.012. View

Wang F, Liu K, Peng J, Luo Y, Tang G, Lin Q . Combination of Xpert MTB/RIF and TBAg/PHA Ratio for Prompt Diagnosis of Active Tuberculosis: A Two-Center Prospective Cohort Study. Front Med (Lausanne). 2020; 7:119. PMC: 7174554. DOI: 10.3389/fmed.2020.00119. View

Mutavhatsindi H, van der Spuy G, Malherbe S, Sutherland J, Geluk A, Mayanja-Kizza H . Validation and Optimization of Host Immunological Bio-Signatures for a Point-of-Care Test for TB Disease. Front Immunol. 2021; 12:607827. PMC: 7952865. DOI: 10.3389/fimmu.2021.607827. View

Wang F, Hou H, Wu S, Zhu Q, Huang M, Yin B . Using the TBAg/PHA ratio in the T-SPOT(®).TB assay to distinguish TB disease from LTBI in an endemic area. Int J Tuberc Lung Dis. 2016; 20(4):487-93. DOI: 10.5588/ijtld.15.0756. View

Musvosvi M, Duffy D, Filander E, Africa H, Mabwe S, Jaxa L . T-cell biomarkers for diagnosis of tuberculosis: candidate evaluation by a simple whole blood assay for clinical translation. Eur Respir J. 2018; 51(3). DOI: 10.1183/13993003.00153-2018. View

10.

Ho J, Bokil N, Nguyen P, Nguyen T, Liu M, Hare N . A transcriptional blood signature distinguishes early tuberculosis disease from latent tuberculosis infection and uninfected individuals in a Vietnamese cohort. J Infect. 2020; 81(1):72-80. DOI: 10.1016/j.jinf.2020.03.066. View

11.

Tang J, Yam W, Chen Z . Mycobacterium tuberculosis infection and vaccine development. Tuberculosis (Edinb). 2016; 98:30-41. DOI: 10.1016/j.tube.2016.02.005. View

12.

Katakura S, Kobayashi N, Hashimoto H, Kamimaki C, Tanaka K, Kubo S . Identification of a novel biomarker based on lymphocyte count, albumin level, and TBAg/PHA ratio for differentiation between active and latent tuberculosis infection in Japan. Tuberculosis (Edinb). 2020; 125:101992. DOI: 10.1016/j.tube.2020.101992. View

13.

Kang W, Wang G, Wu M, Yang K, Er-Tai A, Wu S . Interferon-Gamma Release Assay is Not Appropriate for the Diagnosis of Active Tuberculosis in High-Burden Tuberculosis Settings: A Retrospective Multicenter Investigation. Chin Med J (Engl). 2018; 131(3):268-275. PMC: 5798046. DOI: 10.4103/0366-6999.223860. View

14.

Peng J, Song J, Wang F, Zuo P, Lu Y, Liu W . Harnessing Big Data to Optimize an Algorithm for Rapid Diagnosis of Pulmonary Tuberculosis in a Real-World Setting. Front Cell Infect Microbiol. 2021; 11:650163. PMC: 8012509. DOI: 10.3389/fcimb.2021.650163. View

15.

Acharya M, Pradeep S, Murthy V, Chikkannaiah P, Kambar V, Narayanashetty S . CD38+CD27-TNF-α + on Mtb-specific CD4+ T Cells Is a Robust Biomarker for Tuberculosis Diagnosis. Clin Infect Dis. 2021; 73(5):793-801. DOI: 10.1093/cid/ciab144. View

16.

Morris T, Hoggart C, Chegou N, Kidd M, Oni T, Goliath R . Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa. Front Immunol. 2021; 12:639174. PMC: 7947659. DOI: 10.3389/fimmu.2021.639174. View

17.

Harari A, Rozot V, Bellutti Enders F, Perreau M, Mazza Stalder J, Nicod L . Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat Med. 2011; 17(3):372-6. PMC: 6570988. DOI: 10.1038/nm.2299. View

18.

Ahmed M, Ntinginya N, Kibiki G, Mtafya B, Semvua H, Mpagama S . Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy. Front Immunol. 2018; 9:2247. PMC: 6172348. DOI: 10.3389/fimmu.2018.02247. View

19.

Turner C, Gupta R, Tsaliki E, Roe J, Mondal P, Nyawo G . Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med. 2020; 8(4):407-419. PMC: 7113842. DOI: 10.1016/S2213-2600(19)30469-2. View

20.

Chendi B, Snyders C, Tonby K, Jenum S, Kidd M, Walzl G . A Plasma 5-Marker Host Biosignature Identifies Tuberculosis in High and Low Endemic Countries. Front Immunol. 2021; 12:608846. PMC: 7958880. DOI: 10.3389/fimmu.2021.608846. View