Association of lipoarabinomannan with high density lipoprotein in blood: Implications for diagnostics

Rama Murthy Sakamuri, Dominique N. Price, Myungsun Lee, Sang Nae Cho, Clifton E. Barry, Laura E. Via, Basil I. Swanson, Harshini Mukundan

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


Understanding the pathophysiology of tuberculosis, and the bio-distribution of pathogen-associated molecules in the host is essential for the development of efficient methods of intervention. One of the key virulence factors in the pathology of tuberculosis infection is Lipoarabinomannan (LAM). Previously, we have demonstrated the reliable detection of LAM in urine from tuberculosis patients in a sandwich immunoassay format. We have also applied an ultra-sensitive detection strategy developed for amphiphilic biomarkers, membrane insertion, to the detection of LAM with a limit of detection of 10 fM. Herein, we evaluate the application of membrane insertion to the detection of LAM in patient serum, and demonstrate that the circulating concentrations of 'monomeric' LAM in serum are very low, despite significantly higher concentrations in the urine. Using spiked samples, we demonstrate that this discrepancy is due to the association of LAM with high-density lipoprotein (HDL) nanodiscs in human serum. Indeed, pull-down of HDL nanodiscs from human serum allows for the recovery of HDL-associated LAM. These studies suggest that LAM is likely associated with carrier molecules such as HDL in the blood of patients infected with tuberculosis. This phenomenon may not be limited to LAM in that many pathogen-associated molecular patterns like LAM are amphiphilic in nature and may also be associated with host lipid carriers. Such interactions are likely to affect host-pathogen interactions, pathogen bio-distribution and clearance in the host, and must be thoroughly understood for the effective design of vaccines and diagnostics.

Original languageEnglish
Pages (from-to)301-307
Number of pages7
Issue number3
Publication statusPublished - 2013 May

Bibliographical note

Funding Information:
We thank Mr. K. W. Grace for help in waveguide instrumentation and Mr. A. S. Anderson for SAM chemistry and technical help. We thank the Colorado State University (BEI Resources, operated by the NIAID) for purified LAM and antibodies used in this study. The work was supported by a Department of Energy and Los Alamos National Laboratory LDRD Directed Research Award to Drs. B.T. Korber and B.I. Swanson, and (in part) by the Intramural Research Program of the NIAID , NIH .

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases


Dive into the research topics of 'Association of lipoarabinomannan with high density lipoprotein in blood: Implications for diagnostics'. Together they form a unique fingerprint.

Cite this