Comparative structural study of terminal ends of lipoarabinomannan from mice infected lung tissues and urine of TB positive patient.

Mycobacterium tuberculosis lipoarabinomannan (LAM) is a biomarker for active TB disease. The presence of LAM in urine of TB patients, whether HIV positive or negative has been validated by a gas chromatography/mass spectral method with good specificity (84%) and sensitivity (99%). However, point-of-care (POC) methods to detect TB LAM in urine using immunoassays have poor sensitivity and are limited to only HIV co-infected TB diagnosis. We hypothesized that these disappointing results with the POC methods may be due to the antibodies used in the immunoassays as there could be structural differences between LAM in vivo vs. LAM in vitro. To address this issue, we infected C3HeB/FeJ mice with M. tuberculosis W. Beijing SA161, and purified LAM from the lung. Analysis of these sources of LAM using a panel of existing monoclonal antibodies (mAbs) revealed differences in epitope patterns. Conventionally, the non-reducing termini of LAM are identified by their release with endoarabinanase. These epitopes correspon...