TY - JOUR
T1 - Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes
AU - Magni, Ruben
AU - Rruga, Fatlum
AU - Alsaab, Fahad
AU - Sharif, Sara
AU - Howard, Marissa
AU - Espina, Virginia
AU - Kim, Brianna
AU - Lepene, Benjamin
AU - Lee, Gwenyth
AU - Alayouni, Mohamad A.
AU - Steinberg, Hannah
AU - Araujo, Robyn
AU - Kashanchi, Fatah
AU - Riccardi, Fabio
AU - Morreira, Sargento
AU - Araujo, Antonia
AU - Poli, Fernando
AU - Jaganath, Devan
AU - Semitala, Fred C.
AU - Worodria, William
AU - Andama, Alfred
AU - Choudhary, Alok
AU - Honnen, William J.
AU - Petricoin, Emanuel F.
AU - Cattamanchi, Adithya
AU - Colombatti, Raffaella
AU - de Waard, Jacobus H.
AU - Oberhelman, Richard
AU - Pinter, Abraham
AU - Gilman, Robert H.
AU - Liotta, Lance A.
AU - Luchini, Alessandra
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089542282&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-70669-9
DO - 10.1038/s41598-020-70669-9
M3 - Article
C2 - 32811861
AN - SCOPUS:85089542282
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13944
ER -