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dc.contributor.authorBalagopal, Ashwin
dc.contributor.authorGama, Lucio
dc.contributor.authorFranco, Veronica
dc.contributor.authorRussell, Julia N.
dc.contributor.authorQuinn, Jeffrey
dc.contributor.authorHiggins, Yvonne
dc.contributor.authorSmeaton, Laura Marie
dc.contributor.authorClements, Janice E.
dc.contributor.authorThomas, David L.
dc.contributor.authorGupta, Amita
dc.date.accessioned2013-04-17T18:33:31Z
dc.date.issued2012
dc.identifier.citationBalagopal, Ashwin, Lucio Gama, Veronica Franco, Julia N. Russell, Jeffrey Quinn, Yvonne Higgins, Laura M. Smeaton, Janice E. Clements, David L. Thomas, and Amita Gupta. 2012. Detection of microbial translocation in HIV and SIV infection using the limulus amebocyte lysate assay is masked by serum and plasma. PLoS ONE 7(8): e41258.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10576040
dc.description.abstractObjective: Microbial translocation (MT) is thought to be a major contributor to the pathogenesis of HIV-related immune activation, and circulating lipopolysaccharide (LPS) from Gram-negative bacteria is the principle measurement of this process. However, related research has been impeded by inconsistent LPS test results. Methods: Specimens were obtained from HIV-infected adults enrolled in the PEARLS study (ACTG A5175) and HIV-HCV co-infected participants enrolled in a study of liver disease staging using MRI elastography. Pig-tailed macaque specimens were obtained from SIV-infected and –uninfected animals. Samples were tested for LPS using the LAL assay with diazo-coupling modifications to improve sensitive detection. Results: When exogenous LPS was added to macaque plasma, >25% inhibition of LPS detection was found in 10/10 (100%) samples at 20% plasma concentration compared to control; in contrast 5/10 (50%) samples at 2% plasma concentration (p = 0.07) and 0/10 (0%) at 0.1% plasma concentration (p = 0.004) showed >25% inhibition of LPS detection. Similarly, when LPS was added to human serum, >25% inhibition of LPS detection was found in 5/12 (42%) of samples at 2% serum concentration compared to control, while 0/12 (0%) of samples in 0.1% serum showed >25% inhibition of LPS detection (p = 0.07). Likewise, LPS detection in human sera without exogenous LPS was improved by dilution: LPS was detected in 2/12 (17%) human samples in 2% serum, ranging from 3,436–4,736 pg/mL, compared to 9/12 (75%) samples in 0.1% serum, ranging from 123 pg/mL –60,131 pg/mL (p = 0.016). In a separate validation cohort of HIV-HCV co-infected participants sampled at two different times on the same day, LPS measured in 0.2% plasma and with diazo-coupling was closely correlated between the first and second samples (R = 0.66, p<0.05). Conclusions: Undiluted serum and plasma mask LPS detection. The extent of MT may be substantially underestimated.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0041258en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409852/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectMicrobiologyen_US
dc.subjectImmunityen_US
dc.subjectImmune Activationen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMacaqueen_US
dc.subjectMedicineen_US
dc.subjectClinical Immunologyen_US
dc.subjectImmunopathologyen_US
dc.subjectInfectious Diseasesen_US
dc.subjectViral Diseasesen_US
dc.subjectHIVen_US
dc.subjectRetrovirology and HIV immunopathogenesisen_US
dc.subjectBacterial Diseasesen_US
dc.titleDetection of Microbial Translocation in HIV and SIV Infection Using the Limulus Amebocyte Lysate Assay is Masked by Serum and Plasmaen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorSmeaton, Laura Marie
dc.date.available2013-04-17T18:33:31Z
dc.identifier.doi10.1371/journal.pone.0041258*
dash.contributor.affiliatedSmeaton, Laura


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