title: Highly Multiplexed Proteomic Analysis of Quantiferon Supernatants To Identify Biomarkers of Latent Tuberculosis Infection.
abstract: The tests for diagnosing latent tuberculosis infection (LTBI) are limited by a poor predictive value for identifying people at the highest risk for progressing to active tuberculosis (TB) and have various sensitivities and specificities in different populations. Identifying a more robust signature for LTBI is important for TB prevention and elimination. A pilot study was conducted with samples from immigrants to the United States that were screened for LTBI by the three commercially approved tests, namely, the tuberculin skin test (TST), the Quantiferon-TB Gold in-tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). QFT-GIT supernatants from 13 people with concordant positive results and 26 people with concordant negative results were analyzed via the highly multiplexed SOMAscan proteomic assay. The proteins in the stimulated supernatants that distinguished LTBI from controls included interleukin-2 (IL-2), monocyte chemotactic protein 2 (MCP-2), interferon gamma inducible protein-10 (IP-10), interferon gamma (IFN-γ), tumor necrosis factor superfamily member 14 (TNFSF14, also known as LIGHT), monokine induced by gamma interferon (MIG), and granzyme B (P <0.00001). In addition, antigen stimulation increased the expression of heparin-binding EGF-like growth factor (HB-EGF) and activin AB in LTBI samples. In nil tubes, LIGHT was the most significant marker (P <0.0001) and was elevated in LTBI subjects. Other prominent markers in nonstimulated QFT-GIT supernatants were the complement-3 components C3b, iC3b, and C3d, which were upregulated in LTBI and markedly decreased upon stimulation. We found known and novel proteins that warrant further studies for developing improved tests for LTBI, for predicting progression to active disease, and for discriminating LTBI from active TB.
authors.affiliation: SomaLogic, Inc., Boulder, Colorado, USA.|Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: De Groote
authors.affiliation: Department of Pathology and Laboratory Services, Denver Health, Denver, Colorado, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Higgins
authors.affiliation: SomaLogic, Inc., Boulder, Colorado, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hraha
authors.affiliation: SomaLogic, Inc., Boulder, Colorado, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Wall
authors.affiliation: Department of Pathology and Laboratory Services, Denver Health, Denver, Colorado, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Wilson
authors.affiliation: SomaLogic, Inc., Boulder, Colorado, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Sterling
authors.affiliation: SomaLogic, Inc., Boulder, Colorado, USA.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Janjic
authors.affiliation: Denver Health and Hospital Authority and Denver Public Health, Denver, Colorado, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Reves
authors.affiliation: SomaLogic, Inc., Boulder, Colorado, USA uochsner@somalogic.com Robert.belknap@dhha.org.
authors.forename: Urs A
authors.initials: UA
authors.lastname: Ochsner
authors.affiliation: Denver Health and Hospital Authority and Denver Public Health, Denver, Colorado, USA uochsner@somalogic.com Robert.belknap@dhha.org.
authors.forename: Robert
authors.initials: R
authors.lastname: Belknap
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D054242:Emigrants and Immigrants; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000032:analysis*; D059425:Interferon-gamma Release Tests / Q000379:methods; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D014374:Tuberculin Test / Q000379:methods; D014481:United States; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D020543:Proteome
keywords: biomarkers; diagnosis; immunity; latent infection; proteomics; tuberculosis