Research ArticleTuberculosis

Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity

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Science Translational Medicine  13 Dec 2017:
Vol. 9, Issue 420, eaal2807
DOI: 10.1126/scitranslmed.aal2807

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  • Nanocage-based sequestration of urine lipoarabinomannan for diagnosis of subclinical tuberculosis in HIV co-infected patients?
    • Gabriele Pollara, Clinical Lecturer, University College London
    • Other Contributors:
      • James Brown, Royal Free Hospital
      • Dan Frampton, University College London
      • Harriet Gliddon, University College London
      • Marc Lipman, Royal Free Hospital
      • Timothy D McHugh, University College London
      • Camus Nimmo, University College London
      • Emily Shaw, University College London

    We read with great interest the recent publication by Paris et al in Science Translational Medicine, which explored the coupling of nanocage technology with high-affinity chemical dye baits to improve accuracy of urine-based diagnostics in active Mycobacterium tuberculosis (Mtb) disease (1). This approach, where bacterial components are detected in the readily-collectable urine to diagnose disease remote to the urinary tract, forms the basis of currently available lateral flow tests using lipoarabinomannan (LAM), an outer surface glycan almost unique to Mtb (2,3). However, this test only reaches a sensitivity of around 70% in HIV-Mtb coinfection, and is greatest in the profoundly immunosuppressed with blood CD4 counts below 50 cells/mm3. It is particularly insensitive (<20%) in tuberculosis (TB) patients who are HIV uninfected (4). Thus, WHO recommends that the currently available lateral flow-LAM is not regarded as a screening test for TB, and is only used as an adjunctive test to assist in the diagnosis of TB in HIV co-infected adult patients with low CD4 counts, or who are seriously ill (5).

    The paper by Paris et al elegantly demonstrated that the limitation of the utility of current methods to detect urinary LAM is largely down to LAM load in the sample. Recognising the challenge of raising monoclonal antibodies against complex carbohydrates such as LAM, the authors use the novel high affinity chemical bait RB221 immobilised within an open-mesh hydrogel nano...

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    Competing Interests: None declared.