Exploratory study of proteins in urine of patients with histoplasma antigenuria

Kushnir, Mark M.; Crockett, David K.; Cloud, Joann L.; Ashwood, Edward R.; Rockwood, Alan L.

doi:10.1016/j.jchromb.2011.09.006

Cited by 6 publications

(3 citation statements)

References 22 publications

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“…Another consideration is that histoplasmosis may cause proteinuria, which could limit the ability to detect the antigen. Further studies could evaluate the antigen concentrations during antifungal therapy and at follow-up to better establish this relation as well as renal failure and its influence on clinical results (34).…”

Section: Discussionmentioning

confidence: 99%

Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries

et al. 2018

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Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect infection in regions where histoplasmosis is endemic would dramatically decrease the time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal galactomannan (HGM) enzyme-linked immunosorbent assay (Immuno-Mycologics [IMMY], Norman, OK, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of Using the standard curve provided by the quantitative commercial test, the sensitivity was 98% (95% confidence interval [CI], 95 to 100%) and the specificity was 97% (95% CI, 96 to 99%) (cutoff = 0.5 ng/ml). Semiquantitative results, using a calibrator of 12.5 ng/ml of galactomannan to calculate an enzyme immunoassay index value (EIV) for the samples, showed a sensitivity of 95% (95% CI, 89 to 100%) and a specificity of 98% (95% CI, 96 to 99%) (cutoff ≥ 2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance with reproducible results in both countries, suggesting that it can be used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.

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Section: Discussionmentioning

confidence: 99%

Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries

et al. 2018

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“…Even with the robustness and extensive use of computational biology, it is essential to validate the scientific finding through empirically based knowledge or experimental methods that enhance the confidence and accuracy of predictive computational models ( 63 , 64 ). Accordingly, we used a previously published, unique, and representative data set of peptides obtained directly from urine samples of patients with disseminated histoplasmosis ( 35 , 65 ). In this study, the authors reported that some peptides contained sequences homologous to conserved hypotheticals H. capsulatum proteins.…”

Section: Discussionmentioning

confidence: 99%

Identification and production of novel potential pathogen-specific biomarkers for diagnosis of histoplasmosis

Puerta-Arias,

Isaza Agudelo,

Naranjo Preciado

2023

Microbiol Spectr

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Immunological assays based on the detection of circulating fungal biomarkers are helpful in clinical practice for diagnosing invasive fungal infections. Some of these targeting antigenic components are common to several different fungi. Histoplasmosis is a mycosis caused by the dimorphic fungus Histoplasma capsulatum , which in recent years has gained significant relevance due to the increase in the population susceptible to developing severe clinical forms, including those living with HIV/AIDS. Immunological tests that detect cell wall polysaccharide antigens are among the most used laboratory techniques for diagnosing this mycosis. However, none have shown adequate performance, and cross-reactivity with other fungal pathogens may be observed. Considering that there is a real need to improve the sensitivity and specificity of current diagnostic methods, we explored a novel strategy for the identification of H. capsulatum- specific antigens ( Hc_Ags ) that could be detected in clinical samples during infection based on a computational analysis model that included the application of bioinformatics tools and the analysis of experimental data from transcriptomics and proteomics. The Hc_Ags identified were expressed and purified by eukaryotic and prokaryotic systems. First, the Hc_Ags were used in an in-house immunization model in mice (BALB/c) to obtain Hc_Ag -specific polyclonal antibodies ( Hc_Ag_PAb ). Then, the presence of these antigens in H. capsulatum -yeast culture extracts and the specificity of Hc_Ag_PAb against culture extracts of Candida albicans , Aspergillus fumigatus , Cryptococcus neoformans , Fusarium spp., and Paracoccidioides brasiliensis were confirmed. Finally, we demonstrated the immunoreactivity of these Hc_Ag -specific polyclonal antibodies with urine samples from patients previously diagnosed with histoplasmosis. IMPORTANCE Histoplasmosis is considered one of the most important mycoses due to the increasing number of individuals susceptible to develop severe clinical forms, particularly those with HIV/AIDS or receiving immunosuppressive biological therapies, the high mortality rates reported when antifungal treatment is not initiated in a timely manner, and the limitations of conventional diagnostic methods. In this context, there is a clear need to improve the capacity of diagnostic tools to specifically detect the fungal pathogen, regardless of the patient’s clinical condition or the presence of other co-infections. The proposed novel pathogen-specific biomarkers have the potential to be used in immunodiagnostic platforms and antifungal treatment monitoring in histoplasmosis. In addition, the bioinformatics strategy used in this study could be applied to identify potential diagnostic biomarkers in other models of fungal infection of public health importance.

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“…This integrated LC microchip has the advantage of online sample enrichment prior to chromatographic separation. The Chip Cube system with a standard Agilent LC microchip has been applied for chip‐based LC‐MS analysis in various fields of bioanalytical applications including proteomics , glycomics , as well as clinical and pharmaceutical studies . In order to improve the spray and signal stability, an additional flow path for post‐column makeup flow (MUF) was integrated onto the polyimide LC microchip .…”

Section: Recent Developments In Chip‐based Instrumentationmentioning

confidence: 99%

Microfluidic chip‐based liquid chromatography coupled to mass spectrometry for determination of small molecules in bioanalytical applications: An update

Lin

Fuh

2013

Electrophoresis

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Many microfluidic chip-based LC-MS systems have been utilized for high-throughput analysis in various fields of bioanalytical applications such as proteomic, glycomic, pharmaceutical, and clinical research. This review is an update of a previous review article (Electrophoresis 2012, 33, 635-643) to mainly cover the most recent advancements in chip-based LC-MS for determining small molecules in bioanalysis. First, the different types of microfluidic chip devices for chip-based LC-MS analysis will be discussed. Following the discussion of the recent developments in the chip-based instrumentation, the applications of chip-based LC-MS for determining small molecules, such as glycans, pharmaceutical drugs, drugs of abuse, drug metabolites, and biomarkers in various biological sample matrixes will also be included in this review.

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Exploratory study of proteins in urine of patients with histoplasma antigenuria

Cited by 6 publications

References 22 publications

Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries

Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries

Identification and production of novel potential pathogen-specific biomarkers for diagnosis of histoplasmosis

Microfluidic chip‐based liquid chromatography coupled to mass spectrometry for determination of small molecules in bioanalytical applications: An update

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