Detection of Urinary Excreted Fungal Galactomannan-like Antigens for Diagnosis of Invasive Aspergillosis
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{"title"=>"Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis", "type"=>"journal", "authors"=>[{"first_name"=>"Simon F.", "last_name"=>"Dufresne", "scopus_author_id"=>"37099774100"}, {"first_name"=>"Kausik", "last_name"=>"Datta", "scopus_author_id"=>"24528359600"}, {"first_name"=>"Xinming", "last_name"=>"Li", "scopus_author_id"=>"55364733700"}, {"first_name"=>"Ekaterina", "last_name"=>"Dadachova", "scopus_author_id"=>"7003945571"}, {"first_name"=>"Janet F.", "last_name"=>"Staab", "scopus_author_id"=>"7005093585"}, {"first_name"=>"Thomas F.", "last_name"=>"Patterson", "scopus_author_id"=>"7202308156"}, {"first_name"=>"Marta", "last_name"=>"Feldmesser", "scopus_author_id"=>"7003671781"}, {"first_name"=>"Kieren A.", "last_name"=>"Marr", "scopus_author_id"=>"7005584523"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22900046", "issn"=>"19326203", "sgr"=>"84866619301", "pui"=>"365693235", "scopus"=>"2-s2.0-84866619301", "doi"=>"10.1371/journal.pone.0042736"}, "id"=>"d0413a57-bc11-3a72-b444-950710635d3e", "abstract"=>"Mortality associated with invasive aspergillosis (IA) remains high, partly because of delayed diagnosis. Detection of microbial exoantigens, released in serum and other body fluids during infection, may help timely diagnosis. In course of IA, Aspergillus galactomannan (GM), a well established polysaccharide biomarker, is released in body fluids including urine. Urine is an abundant, safely collected specimen, well-suited for point-of-care (POC) testing, which could play an increasing role in screening for early disease. Our main objective was to demonstrate GM antigenuria as a clinically relevant biological phenomenon in IA and establish proof-of-concept that it could be translated to POC diagnosis. Utilizing a novel IgM monoclonal antibody (MAb476) that recognizes GM-like antigens from Aspergillus and other molds, we demonstrated antigenuria in an experimental animal IA model (guinea pig), as well as in human patients. In addition, we investigated the chemical nature of the urinary excreted antigen in human samples, characterized antigen detection in urine by immunoassays, described a putative assay inhibitor in urine, and indicated means of alleviation of the inhibition. We also designed and used a lateral flow immunochromatographic assay to detect urinary excreted antigen in a limited number of IA patient urine samples. In this study, we establish that POC diagnosis of IA based on urinary GM detection is feasible. Prospective studies will be necessary to establish the performance characteristics of an optimized device and define its optimal clinical use.", "link"=>"http://www.mendeley.com/research/detection-urinary-excreted-fungal-galactomannanlike-antigens-diagnosis-invasive-aspergillosis", "reader_count"=>33, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>11, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>11, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>13, "Chemistry"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>2, "Denmark"=>2, "Chile"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/594003"], "description"=>"<p>Notes:</p>a<p>All antigen preparations were adjusted to 10 µg/ml of carbohydrate content.</p>b<p>Number of isolates tested indicated in brackets (one isolate if no indication).</p>c<p>One isolate was weakly reactive.</p>", "links"=>[], "tags"=>["cross-reactivity"], "article_id"=>264492, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Simon F. Dufresne", "Kausik Datta", "Xinming Li", "Ekaterina Dadachova", "Janet F. Staab", "Thomas F. Patterson", "Marta Feldmesser", "Kieren A. Marr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042736.t001", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MAb476_cross_reactivity_with_other_fungi_a_/264492", "title"=>"MAb476 cross-reactivity with other fungi<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-10 01:14:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/593448"], "description"=>"<p><i>A</i>,<i>B</i> Sandwich ELISA detection of Gal<i>f</i>-containing antigen in BAL and lung homogenates (panel A; N = 5–6) and serum (panel B; N = 2–6) of neutropenic mice, 2 days after aerosol infection with <i>A. fumigatus</i>. <i>C</i>, Organ distribution of <sup>99m</sup>Tc-MAb476 2 days after infection; <i>Top</i>, control mouse: <sup>99m</sup>Tc-label localization in liver and spleen; <i>Bottom</i>, infected mouse: <sup>99m</sup>Tc-label localized in the bladder, representative of 2 independent experiments (N = 3 per group).</p>", "links"=>[], "tags"=>["recognizes", "antigen", "murine", "ia", "localizes", "bladder", "infected"], "article_id"=>263930, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Simon F. Dufresne", "Kausik Datta", "Xinming Li", "Ekaterina Dadachova", "Janet F. Staab", "Thomas F. Patterson", "Marta Feldmesser", "Kieren A. Marr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042736.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MAb476_recognizes_in_vivo_Gal_f_antigen_in_a_murine_model_of_IA_and_localizes_in_the_bladder_of_infected_mice_/263930", "title"=>"MAb476 recognizes <i>in vivo</i> Gal<i>f</i> antigen in a murine model of IA and localizes in the bladder of infected mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-10 01:05:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/593569"], "description"=>"<p><i>A</i>, Comparison amongst PBS/blocking buffer, urine and desalted/dialyzed urine as a diluent for the secondary antibody in indirect ELISA. Antibody concentration to reach half maximal signal (EC<sub>50</sub>) in urine is significantly different than in PBS/blocking buffer or in desalted/dialyzed urine (<i>p</i><0.001, F-test; data combined 3–9 independent assays). <i>B,C</i>, Comparison of PBS or blocking buffer vs. urine or desalted/dialyzed urine as a diluent for the EPA293 in sELISA. <i>Panel B:</i> Antigen concentration to reach half maximal signal (EC<sub>50</sub>) in urine is significantly different than in PBS/blocking buffer or in desalted/dialyzed urine (<i>p</i><0.001, F-test; data combined 9–15 independent assays). <i>Panel C:</i> Comparison of mean signals at 40 ng/ml of EPA293 (urine vs. PBS/Blocking buffer and desalted/dialyzed urine, p = 0.0538 and 0.0009, respectively, unpaired <i>t</i>-test; N = 7–11 independent assays). <i>D,E</i>, Inhibitory effect of urine from 6 healthy volunteers in sELISA; EC<sub>50</sub> values of all urines were significantly different from that of PBS (<i>p</i><0.0001, F-test).</p>", "links"=>[], "tags"=>["inhibitory", "mab476-based", "abrogated", "desalting"], "article_id"=>264053, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Simon F. Dufresne", "Kausik Datta", "Xinming Li", "Ekaterina Dadachova", "Janet F. Staab", "Thomas F. Patterson", "Marta Feldmesser", "Kieren A. Marr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042736.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Urine_has_an_inhibitory_effect_on_MAb476_based_immunoassays_which_is_abrogated_by_desalting_or_dialysis_/264053", "title"=>"Urine has an inhibitory effect on MAb476-based immunoassays, which is abrogated by desalting or dialysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-10 01:07:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/593773"], "description"=>"<p>Processed (10-fold concentration/7 KDa-desalting) urines samples were tested in sELISA; 6 out of 8 infected guinea pigs had detectable antigenuria. Cut off (CO) value equals the mean+3SD of the absorbances of negative controls.</p>", "links"=>[], "tags"=>["detects", "urinary", "excreted", "antigen", "gp", "pulmonary"], "article_id"=>264259, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Simon F. Dufresne", "Kausik Datta", "Xinming Li", "Ekaterina Dadachova", "Janet F. Staab", "Thomas F. Patterson", "Marta Feldmesser", "Kieren A. Marr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042736.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MAb476_detects_a_urinary_excreted_Gal_f_antigen_in_a_GP_model_of_pulmonary_IA_/264259", "title"=>"MAb476 detects a urinary excreted Gal<i>f</i> antigen in a GP model of pulmonary IA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-10 01:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/593694"], "description"=>"<p><i>A</i>, Detection of EPA293 in simulated (spiked) samples after desalting or dialysis at different MWCOs (40 KDa, 7 KDa, 3.5 KDa and 2 KDa); signal curves in PBS or in all treated urine were significantly (comparison of EC<sub>50</sub>; <i>p</i><0.0001, F-test) different than in untreated urine. <i>B</i>, Detection of low, but biologically plausible (50 and 100 ng/ml), EPA293 concentrations in simulated samples after desalting (7 KDa), concentration (5–10 folds; 3 KDa spin-column), or both, compared to no treatment. (*) represents comparisons between a treatment and untreated urine with significant difference (<i>p</i><0.01); (&) represents a trend (<i>p</i> = 0.0613) in comparison between a treatment and untreated urine; (#) represents comparison between concentration/desalting and concentration-only treatments with significant difference (<i>p</i> = 0.0077); all comparisons by One-way ANOVA with a Tukey's post-test for pair-wise comparisons; N = 2–3.</p>", "links"=>[], "tags"=>["antigen", "detection", "simulated", "urine", "samples"], "article_id"=>264177, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Simon F. Dufresne", "Kausik Datta", "Xinming Li", "Ekaterina Dadachova", "Janet F. Staab", "Thomas F. Patterson", "Marta Feldmesser", "Kieren A. Marr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042736.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Desalting_dialysis_and_or_concentration_improve_antigen_detection_in_simulated_urine_samples_in_sELISA_/264177", "title"=>"Desalting/dialysis and/or concentration improve antigen detection in simulated urine samples in sELISA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-10 01:09:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/593883"], "description"=>"<p><i>A</i>, appearance of the assembled LFD; subsequent panels show scanned images of the reaction window. <i>B</i>, Comparison of urine and normal saline (NS) as diluent for EPA293 in LFD. <i>C</i>, Detection of EPA293 in simulated samples after concentration (5–10 folds, 3 KDa MWCO) and desalting (7 KDa MWCO), compared to no treatment. <i>D</i>, Detection of Gal<i>f</i>-containing antigen in processed clinical urine samples; 2 patients have intermediate (++) positive signal and 2 have weak (+) positive signal.</p>", "links"=>[], "tags"=>["lateral", "immunochromatographic", "assay", "detects", "antigen", "simulated", "urine"], "article_id"=>264368, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Simon F. Dufresne", "Kausik Datta", "Xinming Li", "Ekaterina Dadachova", "Janet F. Staab", "Thomas F. Patterson", "Marta Feldmesser", "Kieren A. Marr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042736.g005", "stats"=>{"downloads"=>6, "page_views"=>126, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MAb476_based_Lateral_flow_immunochromatographic_assay_device_LFD_detects_Gal_f_antigen_in_simulated_and_human_urine_samples_/264368", "title"=>"MAb476-based Lateral flow immunochromatographic assay device (LFD) detects Gal<i>f</i> antigen in simulated and human urine samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-10 01:12:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/311929", "https://ndownloader.figshare.com/files/311979", "https://ndownloader.figshare.com/files/312050", "https://ndownloader.figshare.com/files/312104", "https://ndownloader.figshare.com/files/312171", "https://ndownloader.figshare.com/files/312350"], "description"=>"<div><p>Mortality associated with invasive aspergillosis (IA) remains high, partly because of delayed diagnosis. Detection of microbial exoantigens, released in serum and other body fluids during infection, may help timely diagnosis. In course of IA, <em>Aspergillus</em> galactomannan (GM), a well established polysaccharide biomarker, is released in body fluids including urine. Urine is an abundant, safely collected specimen, well-suited for point-of-care (POC) testing, which could play an increasing role in screening for early disease. Our main objective was to demonstrate GM antigenuria as a clinically relevant biological phenomenon in IA and establish proof-of-concept that it could be translated to POC diagnosis. Utilizing a novel IgM monoclonal antibody (MAb476) that recognizes GM-like antigens from <em>Aspergillus</em> and other molds, we demonstrated antigenuria in an experimental animal IA model (guinea pig), as well as in human patients. In addition, we investigated the chemical nature of the urinary excreted antigen in human samples, characterized antigen detection in urine by immunoassays, described a putative assay inhibitor in urine, and indicated means of alleviation of the inhibition. We also designed and used a lateral flow immunochromatographic assay to detect urinary excreted antigen in a limited number of IA patient urine samples. In this study, we establish that POC diagnosis of IA based on urinary GM detection is feasible. Prospective studies will be necessary to establish the performance characteristics of an optimized device and define its optimal clinical use.</p> </div>", "links"=>[], "tags"=>["detection", "urinary", "excreted", "fungal", "galactomannan-like", "antigens", "invasive", "aspergillosis"], "article_id"=>121532, "categories"=>["Cancer", "Microbiology", "Immunology"], "users"=>["Simon F. Dufresne", "Kausik Datta", "Xinming Li", "Ekaterina Dadachova", "Janet F. Staab", "Thomas F. Patterson", "Marta Feldmesser", "Kieren A. Marr"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042736.s001", "https://dx.doi.org/10.1371/journal.pone.0042736.s002", "https://dx.doi.org/10.1371/journal.pone.0042736.s003", "https://dx.doi.org/10.1371/journal.pone.0042736.s004", "https://dx.doi.org/10.1371/journal.pone.0042736.s005", "https://dx.doi.org/10.1371/journal.pone.0042736.s006"], "stats"=>{"downloads"=>23, "page_views"=>50, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Detection_of_Urinary_Excreted_Fungal_Galactomannan_like_Antigens_for_Diagnosis_of_Invasive_Aspergillosis/121532", "title"=>"Detection of Urinary Excreted Fungal Galactomannan-like Antigens for Diagnosis of Invasive Aspergillosis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-08-10 00:25:32"}

PMC Usage Stats | Further Information

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Relative Metric

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