Preliminary Evaluation of a New Prototype Interferon-gamma Release Assay for the Detection of Mycobacterium Tuberculosis-specific T-cell Responses in Patients with Tuberculosis

Overview

Journal Folia Microbiol (Praha)

Publisher Springer

Specialty Microbiology

Date 2025 Mar 3

PMID 40032785

Authors

Marketa Ibrahimova

Karolina Dolezalova

Lubos Baca

Mariia Sukholytka

Evelin Grage-Griebenow

Dorinja Zapf

Sandra Saschenbrecker

Victor Herbst

Emilia Kopecka

Martina Koziar Vasakova

Affiliations

Soon will be listed here.

Abstract

Screening for tuberculosis infections (TBI) using the tuberculin skin test or interferon-gamma release assays (IGRA) is crucial in controlling the global TB burden. This study evaluates the performance of a new IGRA for the detection of T-cell responses against Mycobacterium tuberculosis. Blood samples from 34 adults with tuberculosis disease (TB) and from 30 children with TB, TBI or without TB were analyzed using the prototype Quan-T-Cell TB (EUROIMMUN). The pediatric samples were additionally measured using the established QuantiFERON-TB Gold Plus assay (Qiagen). Clinical performance and inter-assay concordance were analyzed. The prototype Quan-T-Cell TB yielded positivity rates of 88.2% and 100% in adults with TB and children with TBI, respectively, at a specificity of 93.8%. Comparison between the two IGRAs showed positive, negative and overall agreement rates of 100%, 93.8% and 96.3%, respectively, with a kappa score of 0.924 indicating almost perfect agreement. Our study shows promising results of the new prototype Quan-T-Cell TB, as reflected by high concordance with the final diagnosis in adults and children and performance comparable to that of the QuantiFERON IGRA. In individual cases, the data suggest that the prototype Quan-T-Cell TB may be even more consistent with TBI-related clinical findings. Unlike the QuantiFERON assay, the Quan-T-Cell TB has a predefined borderline range, which is advantageous as it may help to differentiate non-specific variation near the cut-off, and fewer sample tubes are required per analysis. The new Quan-T-Cell TB may therefore be a good alternative to the established QuantiFERON IGRA for TBI screening. Further assay optimization is underway, including evaluation studies based on larger patient and control cohorts.

References

Andersen P, Munk M, Pollock J, Doherty T . Specific immune-based diagnosis of tuberculosis. Lancet. 2000; 356(9235):1099-104. DOI: 10.1016/s0140-6736(00)02742-2. View

Behr M, Kaufmann E, Duffin J, Edelstein P, Ramakrishnan L . Latent Tuberculosis: Two Centuries of Confusion. Am J Respir Crit Care Med. 2021; 204(2):142-148. PMC: 8650795. DOI: 10.1164/rccm.202011-4239PP. View

Buonsenso D, Delogu G, Perricone C, Grossi R, Careddu A, De Maio F . Accuracy of QuantiFERON-TB Gold Plus Test for Diagnosis of Mycobacterium tuberculosis Infection in Children. J Clin Microbiol. 2020; 58(6). PMC: 7269397. DOI: 10.1128/JCM.00272-20. View

Buonsenso D, Seddon J, Esposito S, Barcellini L . QuantiFERON-TB Gold Plus Performance in Children: A Narrative Review. Pediatr Infect Dis J. 2023; 42(5):e158-e165. PMC: 10097492. DOI: 10.1097/INF.0000000000003877. View

Cohen A, Mathiasen V, Schon T, Wejse C . The global prevalence of latent tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2019; 54(3). DOI: 10.1183/13993003.00655-2019. View

Ferrara G, Losi M, Meacci M, Meccugni B, Piro R, Roversi P . Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2005; 172(5):631-5. DOI: 10.1164/rccm.200502-196OC. View

Fox A, Jeffries D, Hill P, Hammond A, Lugos M, Jackson-Sillah D . ESAT-6 and CFP-10 can be combined to reduce the cost of testing for Mycobacterium tuberculosis infection, but CFP-10 responses associate with active disease. Trans R Soc Trop Med Hyg. 2007; 101(7):691-8. DOI: 10.1016/j.trstmh.2007.03.001. View

Getahun H, Matteelli A, Abubakar I, Abdel Aziz M, Baddeley A, Barreira D . Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J. 2015; 46(6):1563-76. PMC: 4664608. DOI: 10.1183/13993003.01245-2015. View

Greveson K, Murray C, Toumpanakis C, Epstein O, Hamilton M, Lipman M . Interferon γ-release assays for detecting latent tuberculosis infection in patients scheduled for anti-TNFα therapy. Frontline Gastroenterol. 2017; 2(1):26-31. PMC: 5517191. DOI: 10.1136/fg.2010.000356. View

10.

Hamada Y, den Boon S, Cirillo D, Penn-Nicholson A, Ruhwald M, Menzies D . Framework for the evaluation of new tests for tuberculosis infection. Eur Respir J. 2021; 58(2). PMC: 8374690. DOI: 10.1183/13993003.04078-2020. View

11.

Herrera V, Perry S, Parsonnet J, Banaei N . Clinical application and limitations of interferon-gamma release assays for the diagnosis of latent tuberculosis infection. Clin Infect Dis. 2011; 52(8):1031-7. DOI: 10.1093/cid/cir068. View

12.

Huang C, Ruan S, Tsai Y, Kuo P, Ku S, Lee P . Effects of acute critical illnesses on the performance of interferon-gamma release assay. Sci Rep. 2016; 6:19972. PMC: 4726381. DOI: 10.1038/srep19972. View

13.

Infantino M, Tsalouchos A, Russo E, Laudicina S, Grossi V, Lari B . Assessing T-Cell Immunity in Kidney Transplant Recipients with Absent Antibody Production after a 3rd Dose of the mRNA-1273 Vaccine. Int J Mol Sci. 2022; 23(20). PMC: 9604095. DOI: 10.3390/ijms232012333. View

14.

Kim W, Choi J, Cheon J, Kim I, Yeon K, Lee H . Pulmonary tuberculosis in infants: radiographic and CT findings. AJR Am J Roentgenol. 2006; 187(4):1024-33. DOI: 10.2214/AJR.04.0751. View

15.

Landis J, Koch G . The measurement of observer agreement for categorical data. Biometrics. 1977; 33(1):159-74. View

16.

Latorre I, De Souza-Galvao M, Ruiz-Manzano J, Lacoma A, Prat C, Altet N . Evaluating the non-tuberculous mycobacteria effect in the tuberculosis infection diagnosis. Eur Respir J. 2010; 35(2):338-42. DOI: 10.1183/09031936.00196608. View

17.

Lewinsohn D, Leonard M, LoBue P, Cohn D, Daley C, Desmond E . Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017; 64(2):111-115. PMC: 5504475. DOI: 10.1093/cid/ciw778. View

18.

Lin P, Flynn J . The End of the Binary Era: Revisiting the Spectrum of Tuberculosis. J Immunol. 2018; 201(9):2541-2548. PMC: 6217958. DOI: 10.4049/jimmunol.1800993. View

19.

Lin S, Desmond E . Molecular diagnosis of tuberculosis and drug resistance. Clin Lab Med. 2014; 34(2):297-314. DOI: 10.1016/j.cll.2014.02.005. View

20.

Mancuso J, Mody R, Olsen C, Harrison L, Santosham M, Aronson N . The Long-term Effect of Bacille Calmette-Guérin Vaccination on Tuberculin Skin Testing: A 55-Year Follow-Up Study. Chest. 2017; 152(2):282-294. DOI: 10.1016/j.chest.2017.01.001. View