RESUMO
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.
Assuntos
Lipopolissacarídeos/análise , Tuberculose/diagnóstico , Tuberculose/imunologia , Adulto , Coinfecção/urina , Epitopos/imunologia , Feminino , Guiné-Bissau , Infecções por HIV/urina , Humanos , Imunoensaio/métodos , Testes Imunológicos/métodos , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/urina , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Peru , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Tuberculose/classificação , Tuberculose Pulmonar/microbiologia , Uganda , Estados Unidos , VenezuelaRESUMO
Neutralizing activity of secretory immunoglobulin A (S-IgA) directed against the V1/V2 domain of HIV-1 was studied in parotid saliva of HIV-1- infected patients in Colombian and French cohorts. Purified V1/V2-specific S-IgA antibodies were found to neutralize clades A, B and C primary isolates in five out 76 and 82 patients from each cohort, respectively. These results suggest that neutralizing S-IgA antibodies targeting the V1/V2 domain may provide protection against HIV-1 infection in vivo and may be beneficial in mucosal vaccines.