title: A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases.
abstract: The goal of this study was to identify a host gene signature that can distinguish tuberculosis (TB) from other pulmonary diseases (OPD). We conducted real-time PCR on whole blood samples from patients in Brazil. TB and OPD patients (asthma and non-TB pneumonia) differentially expressed granzyme A (GZMA), guanylate binding protein 5 (GBP5) and Fc gamma receptor 1A (CD64). Receiver operating characteristic, tree classification and random forest analyses were applied to evaluate the discriminatory power of the three genes and find the gene panel most predictive of patients' disease classification. Tree classification produced a model based on GBP5 and CD64 expression. In random forest analysis, the combination of the three genes provided a robust biosignature to distinguish TB from OPD with 95% specificity and 93% sensitivity. Our results suggest that GBP5 and CD64 in tandem may be the most predictive combination. However, GZMA contribution to the prediction model requires further investigation. Regardless, these three genes show promise as a rapid diagnostic marker separating TB from OPD.
authors.affiliation: Fundação Estadual de Produção e Pesquisa em Saúde, Avenida Ipiranga, 5400, Porto Alegre, RS 90610-000, Brazil; Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil. Electronic address: lauxlc@yahoo.com.br.
authors.forename: Lucas
authors.initials: L
authors.lastname: Laux da Costa
authors.affiliation: Division of Infectious Disease and Vaccinology, School of Public Health, University of California, 530 Li Ka Shing, Berkeley, CA 94720, USA. Electronic address: mdelcroix@berkeley.edu.
authors.forename: Melaine
authors.initials: M
authors.lastname: Delcroix
authors.affiliation: Fundação Estadual de Produção e Pesquisa em Saúde, Avenida Ipiranga, 5400, Porto Alegre, RS 90610-000, Brazil. Electronic address: dallacostaer@gmail.com.
authors.forename: Elis R
authors.initials: ER
authors.lastname: Dalla Costa
authors.affiliation: Programa de Pós Graduação em Epidemiologia da Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400, Porto Alegre, RS 90035-003, Brazil. Electronic address: ppgepid@ufrgs.br.
authors.forename: Isaías V
authors.initials: IV
authors.lastname: Prestes
authors.affiliation: Fundação Estadual de Produção e Pesquisa em Saúde, Avenida Ipiranga, 5400, Porto Alegre, RS 90610-000, Brazil; Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil. Electronic address: marianamilano@hotmail.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Milano
authors.affiliation: Division of Epidemiology, School of Public Health, University of California, 50 University Hall, Berkeley, CA 94720, USA. Electronic address: ssfrancis@berkeley.edu.
authors.forename: Steve S
authors.initials: SS
authors.lastname: Francis
authors.affiliation: Hospital Sanatório Partenon, Avenida Bento Gonçalves, 3722, Porto Alegre, RS 90650-001, Brazil. Electronic address: giunis@terra.com.br.
authors.forename: Gisela
authors.initials: G
authors.lastname: Unis
authors.affiliation: Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil; Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil. Electronic address: denise.rossato@terra.com.br.
authors.forename: Denise R
authors.initials: DR
authors.lastname: Silva
authors.affiliation: Division of Infectious Disease and Vaccinology, School of Public Health, University of California, 530 Li Ka Shing, Berkeley, CA 94720, USA. Electronic address: lwriley@berkeley.edu.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Riley
authors.affiliation: Fundação Estadual de Produção e Pesquisa em Saúde, Avenida Ipiranga, 5400, Porto Alegre, RS 90610-000, Brazil; Universidade Luterana do Brazil, Avenida Farroupilha, 8001, Bairro São José, Canoas, RS 92425-900, Brazil. Electronic address: mrossett@terra.com.br.
authors.forename: Maria L R
authors.initials: ML
authors.lastname: Rossetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001249:Asthma / Q000175:diagnosis / Q000235:genetics; D001938:Brazil; D003663:Decision Trees; D003937:Diagnosis, Differential; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D005819:Genetic Markers; D053804:Granzymes / Q000235:genetics*; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D011014:Pneumonia / Q000175:diagnosis / Q000235:genetics; D011237:Predictive Value of Tests; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D017452:Receptors, IgG / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000235:genetics / Q000382:microbiology; D055815:Young Adult
chemical_list: C489017:FCGR1A protein, human; C528873:GBP5 protein, human; D005819:Genetic Markers; D017452:Receptors, IgG; D053804:Granzymes; C509212:GZMA protein, human; D019204:GTP-Binding Proteins
keywords: Biomarkers; CD64; Diagnostics; GBP5; GZMA; Tuberculosis