Evidence map›Paper›PMID 33826643›Full record

Trial reportPloS one2021

Interaction of amphiphilic lipoarabinomannan with host carrier lipoproteins in tuberculosis patients: Implications for blood-based diagnostics.

Shailja Jakhar, Ramamurthy Sakamuri, Dung Vu, Priya Dighe, Loreen R Stromberg, Laura Lilley, Nicolas Hengartner, Basil I Swanson, Emmanuel Moreau, Susan E Dorman and 1 more

Open access · goldAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Shailja JakharPhysical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Ramamurthy SakamuriPhysical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Dung VuPhysical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Priya DigheBiosecurity and Public Health, Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Loreen R StrombergPhysical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Laura LilleyPhysical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Nicolas HengartnerTheoretical Biology and Biophysics, Theory Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Basil I SwansonBiosecurity and Public Health, Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Emmanuel MoreauFoundation for Innovative New Diagnostics, Geneva, Switzerland.
Susan E DormanDepartment of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Harshini MukundanPhysical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.ORCID 0000-0002-0931-0545
Los Alamos National Laboratory · USFIND · CHMedical University of South Carolina · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipoarabinomannan (LAM), an amphiphilic lipoglycan of the Mycobacterium tuberculosis cell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to "concentrate" LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms, but no positive culture for M. tuberculosis, and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach, but that further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.

Indexed as

AdultFemaleHumansLipopolysaccharidesLipoproteinsMaleMycobacterium tuberculosisTuberculosislipoarabinomannanLipopolysaccharidesLipoproteins

Identifiers

PMID33826643
PMCPMC8026062
OpenAlexW3149036111

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.