title: Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscellaneous Inflammatory Underlying Conditions.
abstract: New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-γ, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-γ, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette-Guérin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative-stimulated IFN-γ, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-γ, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-γ, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki , Helsinki , Finland.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Savolainen
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Medicine, Division of Infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland; Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kantele
authors.affiliation: Heart and Lung Center, Helsinki University Central Hospital , Helsinki , Finland.
authors.forename: Aija
authors.initials: A
authors.lastname: Knuuttila
authors.affiliation: Länsi-Uusimaa Hospital , Tammisaari , Finland.
authors.forename: Liana
authors.initials: L
authors.lastname: Pusa
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; Laboratory Division (HUSLAB), Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Karttunen
authors.affiliation: Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital , Helsinki , Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Valleala
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; Eastern Finland Laboratory Centre Joint Authority Enterprise, Mikkeli, Finland.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tuuminen
keywords: IFN-γ; IL-17; IL-4; LTBI; active TB; mRNA