Table 3 Potential mechanisms of the association between urinary LAM detection and increased mortality risk

Urinary LAM is a marker of disseminated TB and higher mycobacterial burden, which is associated with a worse prognosis

• Urinary LAM is due to haematogenously disseminated renal TB

Cox et al. 2015 [26]

• HIV-TB patients with mycobacteraemia have a higher mortality

Cummings et al. 2015 [56]

• Higher concentrations of urinary LAM are associated with higher mycobacterial burden

Kerkhoff et al. 2014 [19]

Urinary LAM is a proxy for a low CD4 cell count

• HIV-TB patients with positive urinary LAM tests have lower CD4 cell counts

Minion et al. 2011 [11]

• Mortality is higher in patients with lower CD4 cell counts

Gupta et al. 2015 [34]

LAM itself contributes to immunosuppression, impairing host defences against MTB and other opportunistic infections

• LAM is a virulence factor for MTB

Strohmeier et al. 1999 [35]

• LAM inhibits immune responses, with direct inhibitory effects on macrophage activation and function

Mishra et al. 2011 [38]

Neyrolles et al. 2011 [41]

• LAM inhibits pro-inflammatory cytokines, e.g. IL-12 and TNF-α

• LAM enhances the secretion of anti-inflammatory cytokines, e.g. IL-10