Antigen-specific skin tests for detecting tuberculosis infection before biologic and targeted therapy: molecular and immunological foundations and clinical interpretation

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Abstract

Introduction. The expanding use of biologic agents, targeted synthetic drugs, and other immunosuppressive treatments has increased the importance of testing for tuberculosis infection in patients at risk of developing tuberculosis disease. Mycobacterium tuberculosis antigen-based skin tests using ESAT-6 and CFP-10 constitute a new class of immunological tests that combine a specific antigenic platform with the operational format of a skin test.

Objective. To summarize the molecular and immunological basis, diagnostic capabilities and limitations of Mycobacterium tuberculosis antigen-based skin tests and to define their place in the comprehensive assessment of patients before biological, targeted, and immunosuppressive therapy.

Material and methods. A narrative review of publications indexed in PubMed, Scopus, Web of Science, and eLibrary was conducted, together with an analysis of World Health Organization documents and professional clinical recommendations. Studies addressing the molecular properties of ESAT-6 and CFP-10, the diagnostic performance of the tuberculin skin test, interferon-gamma release assays, and antigen-based skin tests, as well as the risk of tuberculosis associated with drug-induced immunosuppression, were considered. The principal search period was 2015 – 2026; earlier fundamental studies were also included.

Results. ESAT-6 and CFP-10 are encoded within the RD1 region and secreted through the ESX-1 system, which is associated with the virulence of the M. tuberculosis complex. The absence of a functional RD1 region in Mycobacterium bovis (BCG) vaccine strains increases the specificity of ESAT-6/CFP-10-based tests compared with the tuberculin skin test. The TBST products evaluated by WHO include Cy-Tb, previously studied as C-Tb, C-TST, and the ESAT-6/CFP-10 recombinant antigen-based skin test used in the Russian Federation. TBSTs detect an antigen-specific cell-mediated immune response but cannot independently distinguish tuberculosis infection from active tuberculosis disease. In patients with severe immunosuppression, a negative skin test may result from impaired T-cell responsiveness. TBST results should therefore be interpreted together with clinical, epidemiological, radiological, and laboratory findings.

Conclusion. Antigen-based skin tests may be used as one component of the comprehensive assessment of patients before biological, targeted, and immunosuppressive therapy. Test selection and interpretation should take into account the clinical and epidemiological risk, the degree of immune impairment, the class of planned treatment, and applicable national clinical algorithms.

About the authors

Dmitry A. Kudlay

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University; The Federal Scientific “State Research Center Institute of Immunology” of the Federal Medical and Biological Agency of Russia

Author for correspondence.
Email: kudlay_d_a@staff.sechenov.ru
ORCID iD: 0000-0003-1878-4467

Professor, Department of Pharmacology, Institute of Pharmacy, FSAEI HE I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Deputy Dean for Scientific and Technological Development, Faculty of Bioengineering and Bioinformatics, Professor, Department of Pharmacognosy and Industrial Pharmacy, Faculty of Fundamental Medicine, FSBEI HE M.V. Lomonosov Moscow State University; Leading Researcher, Laboratory of Personalized Medicine and Molecular Immunology No.71, The Federal Scientific “State Research Center Institute of Immunology” of the Federal Medical and Biological Agency of Russia. Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences

Russian Federation, Trubetskaya str., 8, build. 2, Moscow, 119991; Leninskie Gory, 1, Moscow, 119991; Kashirskoye Shosse, 24, 115522, Moscow

Elena A. Borodulina

Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University

Email: borodulinbe@yandex.ru
ORCID iD: 0000-0002-3063-1538

Head of the Department of Phthisiology and Pulmonology, Samara State Medical University. Doctor of Medical Sciences, Professor

Russian Federation, Leninskie Gory, 1, Moscow, 119991

Evgeniya A. Amosova

Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University

Email: amosova@mail.ru
ORCID iD: 0000-0002-6209-663X

Associate Professor of the Department of Phthisiology and Pulmonology, Samara State Medical University. Candidate of Medical Sciences, Associate Professor

Russian Federation, Leninskie Gory, 1, Moscow, 119991

Maria A. Lvova

Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University

Email: mari-lvova@mail.ru
ORCID iD: 0009-0009-1788-933X

Resident, Department of Pediatrics, Institute of Professional Education, Samara State Medical University

Russian Federation, Leninskie Gory, 1, Moscow, 119991

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