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

From: Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis

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
  1. LAM lipoarabinomannan, MTB Mycobacterium tuberculosis, TB tuberculosis