title: The tuberculin skin test increases the responses measured by T cell interferon-gamma release assays.
abstract: RUTI is a vaccine consisting of Mycobacterium tuberculosis bacilli grown in stress conditions that is fragmented, detoxified and liposomed. RUTI was designed to shorten the treatment of latent tuberculosis infection (LTBI) with isoniazid from 9 months to just 1 month, by additional treatment with two inoculations of RUTI 4 weeks apart. During the validation process for monitoring the immunogenicity of administration of RUTI in a Phase I clinical trial, the question arose whether to introduce the tuberculin skin test (TST) in the screening of non-LTBI volunteers. This study was designed to evaluate the effect of TST on subsequent different T-cell interferon-gamma release assay (TIGRA) responses, using a spectrum of M. tuberculosis-related antigens (ESAT-6, CFP-10, 16 kDa, 19 kDa, MPT64, Ag 85B, 38 kDa, hsp65, PPD and BCG). The results showed an increase in post-TST response even in non-LTBI subjects for most antigens tested, as measured both by whole blood assay (WBA) and ELISPOT. Increased ELISPOT response decreased toward pre-TST levels within 1 month whereas the WBA response did not. Taking into account that there is no definitive correlation between TST and TIGRA tests to diagnose LTBI and the feasibility that TST might alter the immune monitoring included in clinical trials, these data suggest that TST determination should be carefully planned to avoid any interference with TIGRA.
authors.affiliation: Unitat de Tuberculosi Experimental, Fundacio Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Vilaplana
authors.forename: J
authors.initials: J
authors.lastname: Ruiz-Manzano
authors.forename: O
authors.initials: O
authors.lastname: Gil
authors.forename: F
authors.initials: F
authors.lastname: Cuchillo
authors.forename: E
authors.initials: E
authors.lastname: Montané
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.forename: R
authors.initials: R
authors.lastname: Spallek
authors.forename: V
authors.initials: V
authors.lastname: Ausina
authors.forename: P J
authors.initials: PJ
authors.lastname: Cardona
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014373:Tuberculin; D007371:Interferon-gamma