Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes

Ruben Magni, Fatlum Rruga, Fahad Alsaab, Sara Sharif, Marissa Howard, Virginia Espina, Brianna Kim, Benjamin Lepene, Gwenyth Lee, Mohamad A. Alayouni, Hannah Steinberg, Robyn Araujo, Fatah Kashanchi, Fabio Riccardi, Sargento Morreira, Antonia Araujo, Fernando Poli, Devan Jaganath, Fred C. Semitala, William WorodriaAlfred Andama, Alok Choudhary, William J. Honnen, Emanuel F. Petricoin, Adithya Cattamanchi, Raffaella Colombatti, Jacobus H. de Waard, Richard Oberhelman, Abraham Pinter, Robert H. Gilman, Lance A. Liotta, Alessandra Luchini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number13944
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General

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