Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes

Area of Science:

• Immunology
• Infectious Diseases
• Diagnostics

Background:

• Active tuberculosis (TB) diagnosis remains a challenge, especially in diverse populations.
• Current urinary liporabinomannan (LAM) testing is often limited to HIV-coinfected TB patients.
• Accurate TB diagnostics are crucial for preventing TB-related mortality.

Purpose of the Study:

• To evaluate the diagnostic performance of urinary LAM in HIV-negative, pediatric, adult, pulmonary, and extrapulmonary TB patients.
• To assess the utility of three distinct monoclonal antibodies (MoAb1, CS35, A194) targeting LAM epitopes.
• To identify potential sources of assay variability and the impact of comorbidities like HIV and diabetes.

Main Methods:

• A study involving 430 microbiologically confirmed TB patients and controls from multiple countries.
• Utilized a one-sided immunoassay with three monoclonal antibodies recognizing different LAM epitopes.
• Employed blinded cohorts and evaluated assay variability and comorbidities.

Main Results:

• All tested antibodies demonstrated the ability to differentiate TB-positive from TB-negative patients.
• The average response from three antibodies achieved a ROC AUC of 0.90 (90% sensitivity, 73.5% specificity).
• MoAb1 antibody showed superior performance, particularly in pediatric and extrapulmonary TB cases, with high sensitivity and specificity.

Conclusions:

• Urinary LAM testing holds significant potential for active TB detection across a broader patient spectrum.
• The MoAb1 antibody, targeting a specific LAM epitope, is a promising novel analyte for diagnosing active TB, especially in pediatric and extrapulmonary forms.
• This diagnostic approach could be transformative in preventing TB deaths globally.