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Table 3 Potential mechanisms of the association between urinary LAM detection and increased mortality risk
| Potential mechanism | Evidence | References |
|---|---|---|
| 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 |
