title: Discriminative expression of whole blood genes in HIV patients with latent and active TB in Ethiopia.
abstract: Transcriptomic host biomarkers could assist in developing effective diagnostics, vaccines and therapeutics for tuberculosis (TB). However, different biomarkers may be discriminatory in different populations depending on the host and bacillary genetics and HIV infection, and need to be addressed.
  
  
  
  The expression levels of 45 genes that are known to be involved in or affected by TB pathogenesis were analyzed using dual color Reverse Transcriptase Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) assay in whole blood of 106 HIV positive individuals including active TB patients (TB(+)HIV(+), n = 29), and non TB patients that are tuberculin skin test positive (TST+) (TST(+)HIV(+), n = 26), or TST negative (TST(-)HIV(+), n = 51).
  
  
  
  Between the two clinical groups (TB(+)HIV(+) vs. TST(-)HIV(+)) 8 genes were differently expressed (CCL19, CD14, CD8A, FPR1, IL7R, CCL22, TNFRSF1A, and FCGR1A); between TB(+)HIV(+) vs. TST(+)HIV(+), 6 genes (CD14, IL7R, TIMP2, CCL22, TNFRSF1A, and FCGR1A) were differently expressed. Since no difference in gene expression was revealed between TST(+)HIV(+) vs. TST(-)HIV(+), we clustered both the TST(+)HIV(+) and TST(-)HIV(+) individuals as one group (TST(+/-)HIV(+)) and compared gene expression with TB(+)HIV(+) patients. Thus, the results revealed that the levels of five genes (CD8A, TIMP2, CCL22, FCGR1A and TNFRSF1A) were the most accurate single gene markers for differentiation between TB(+)HIV(+) and TST(+/-)HIV(+), with AUCs of 0.71, 0.71, 0.79, 0.83 and 0.73, respectively. However, the combination of two genes (CCL22 + FCGR1A) and FCGR1A alone were the most accurate marker for differentiation between the two groups (TB(+)HIV(+) and TST(+/-)HIV(+)) with AUC of 0.85 and 0.83, respectively.
  
  
  
  We showed that five genes (CD8A, TIMP2, CCL22, FCGR1A and TNFRSF1A), specifically FCGR1A and CCL22 have the potential to discriminate active TB from non-active TB in HIV patients in Ethiopia and could be used to improve diagnostic tools for active TB in HIV patients, and to understand the pathogenesis of TB/HIV coinfection.
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: dkassa2003@gmail.com.
authors.forename: Desta
authors.initials: D
authors.lastname: Kassa
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Ran
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wilco de
authors.initials: W
authors.lastname: Jager
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: van den Broek
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Jacobi
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia; Axum University, Tigray, Ethiopia.
authors.forename: Muluberhan
authors.initials: M
authors.lastname: Mekonen
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Public Health Institute (EPHI), Addis Ababa, Ethiopia.
authors.forename: Tsehaynesh
authors.initials: T
authors.lastname: Messele
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariëlle C
authors.initials: MC
authors.lastname: Haks
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom H M
authors.initials: THM
authors.lastname: Ottenhoff
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D060085:Coinfection / Q000175:diagnosis / Q000235:genetics; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: Biomarker; Host gene; Tuberculosis