1. Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes.
- Author
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Magni R, Rruga F, Alsaab FM, Sharif S, Howard M, Espina V, Kim B, Lepene B, Lee G, Alayouni MA, Steinberg H, Araujo R, Kashanchi F, Riccardi F, Morreira S, Araujo A, Poli F, Jaganath D, Semitala FC, Worodria W, Andama A, Choudhary A, Honnen WJ, Petricoin EF 3rd, Cattamanchi A, Colombatti R, de Waard JH, Oberhelman R, Pinter A, Gilman RH, Liotta LA, and Luchini A
- Subjects
- Adult, Coinfection urine, Epitopes immunology, Female, Guinea-Bissau, HIV Infections urine, Humans, Immunoassay methods, Immunologic Tests methods, Lipopolysaccharides immunology, Lipopolysaccharides urine, Male, Middle Aged, Mycobacterium tuberculosis immunology, Peru, Point-of-Care Systems, Sensitivity and Specificity, Tuberculosis classification, Tuberculosis, Pulmonary microbiology, Uganda, United States, Venezuela, Lipopolysaccharides analysis, Tuberculosis diagnosis, Tuberculosis immunology
- Abstract
An accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients. We measured 430 microbiologically confirmed pretreatment tuberculosis patients and controls from Peru, Guinea Bissau, Venezuela, Uganda and the United States using three monoclonal antibodies, MoAb1, CS35, and A194, which recognize distinct LAM epitopes, a one-sided immunoassay, and blinded cohorts. We evaluated sources of assay variability and comorbidities (HIV and diabetes). All antibodies successfully discriminated TB positive from TB negative patients. ROAUC from the average of three antibodies' responses was 0.90; 95% CI 0.87-0.93, 90% sensitivity, 73.5% specificity (80 pg/mL). MoAb1, recognizing the 5-methylthio-D-xylofuranose(MTX)-mannose(Man) cap epitope, performed the best, was less influenced by glycosuria and identified culture positive pediatric (N = 19) and extrapulmonary (N = 24) patients with high accuracy (ROAUC 0.87, 95% CI 0.77-0.98, 0.90 sensitivity 0.80 specificity at 80 pg/mL; ROAUC = 0.96, 95% CI 0.92-0.99, 96% sensitivity, 80% specificity at 82 pg/mL, respectively). The MoAb1 antibody, recognizing the MTX-Man cap epitope, is a novel analyte for active TB detection in pediatric and extrapulmonary disease.
- Published
- 2020
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