Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Detection of anti-Pneumocystis jirovecii antibodies in human serum using a recombinant synthetic multi-epitope kexin-based antigen.

ABSTRACT: Interest in the detection of specific anti-Pneumocystis jirovecii antibodies has emerged as less-invasive alternative diagnostic approaches. Here is presented the performance of an ELISA based on a recombinant synthetic multi-epitope kexin 1 (Kex1) antigen of P. jirovecii, previously developed. Results showed that IgM anti-Kex1 levels were found significantly increased in patients with Pneumocystis pneumonia (PcP) compared with non-PcP cases (p < 0.001), allowing a diagnostic performance of PcP with a 70.8% sensitivity and a 75.0% specificity. These results suggest that this Kex1-based ELISA is a promising tool toward the serodiagnosis of PcP when the standard methods are difficult to perform.

SUBMITTER: Tomas AL

PROVIDER: S-EPMC7561569 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Detection of anti-Pneumocystis jirovecii antibodies in human serum using a recombinant synthetic multi-epitope kexin-based antigen.

Tomás Ana Luísa AL Cardoso Fernando F de Sousa Bruno B Matos Olga O

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 20200616 11

Interest in the detection of specific anti-Pneumocystis jirovecii antibodies has emerged as less-invasive alternative diagnostic approaches. Here is presented the performance of an ELISA based on a recombinant synthetic multi-epitope kexin 1 (Kex1) antigen of P. jirovecii, previously developed. Results showed that IgM anti-Kex1 levels were found significantly increased in patients with Pneumocystis pneumonia (PcP) compared with non-PcP cases (p < 0.001), allowing a diagnostic performance of PcP ...[more]

PMID: 32557324

Similar Datasets

Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii.

Project description:Diagnosis of Pneumocystis pneumonia (PcP) relies on the detection of P. jirovecii in respiratory specimens obtained by invasive techniques. Thus, the development of a serological test is urgently needed as it will allow the diagnosis of PcP using blood, an inexpensive and non-invasive specimen. This study aims to combine the production of a multi-epitope synthetic recombinant antigen (RSA) and an ELISA test for detection of anti-P. jirovecii antibodies, in order to develop a new approach for PcP diagnosis. The RSA was selected and designed based on the study of the immunogenicity of the carboxyl-terminal domain of the major surface glycoprotein. This antigen was purified and used as an antigenic tool in an ELISA technique for detection of Ig, IgG and IgM antibodies anti-P. jirovecii (patent-pending no. PT109078). Serum specimens from 88 patients previously categorized in distinct clinical subgroups and 17 blood donors, were analysed. The IgM anti-P. jirovecii levels were statistically increased in patients with PcP (p?=?0.001) and the ELISA IgM anti-P. jirovecii test presented a sensitivity of 100% and a specificity of 80.8%, when associated with the clinical diagnosis criteria. This innovative approach, provides good insights about what can be done in the future serum testing for PcP diagnosis.

| S-EPMC5099754 | biostudies-literature

Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii.

Project description:Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4+ T cells were depleted, and the mice were exposed to Pneumocystis murina Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii Potential orthologs of Pca1 have been identified in P. jirovecii Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.

| S-EPMC5364303 | biostudies-literature

Pneumocystis jirovecii

Project description:Pathogenic fungus that causes pneumonia in immunocompromised persons

| PRJNA20531 | ENA

Pneumocystis jirovecii

Project description:Pneumocystis jirovecii Metagenome

| PRJNA782857 | ENA

Serum antibody levels to the Pneumocystis jirovecii major surface glycoprotein in the diagnosis of P. jirovecii pneumonia in HIV+ patients.

Project description:BackgroundPneumocystis jirovecii remains an important cause of fatal pneumonia (Pneumocystis pneumonia or PcP) in HIV+ patients and other immunocompromised hosts. Despite many previous attempts, a clinically useful serologic test for P. jirovecii infection has never been developed.Methods/principal findingsWe analyzed serum antibody responses to the P. jirovecii major surface glycoprotein recombinant fragment C1 (MsgC1) in 110 HIV+ patients with active PcP (cases) and 63 HIV+ patients with pneumonia due to other causes (controls) by an enzyme-linked immunosorbent assay (ELISA). The cases had significantly higher IgG and IgM antibody levels to MsgC1 than the controls at hospital admission (week 0) and intervals up to at least 1 month thereafter. The sensitivity, specificity and positive predictive value (PPV) of IgG antibody levels increased from 57.2%, 61.7% and 71.5% at week 0 to 63.4%, 100%, and 100%, respectively, at weeks 3-4. The sensitivity, specificity and PPV of IgM antibody levels rose from 59.7%, 61.3%, and 79.3% at week 0 to 74.6%, 73.7%, and 89.8%, respectively, at weeks 3-4. Multivariate analysis revealed that a diagnosis of PcP was the only independent predictor of high IgG and IgM antibody levels to MsgC1. A high LDH level, a nonspecific marker of lung damage, was an independent predictor of low IgG antibody levels to MsgC1.Conclusions/significanceThe results suggest that the ELISA shows promise as an aid to the diagnosis of PCP in situations where diagnostic procedures cannot be performed. Further studies in other patient populations are needed to better define the usefulness of this serologic test.

| S-EPMC3000336 | biostudies-literature

Humans Are Selectively Exposed to Pneumocystis jirovecii.

Project description:Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal spore dispersal and transmission is poorly understood. The democratization of shotgun metagenomics allows us to explore important questions about fungal propagation. We focus on Pneumocystis, a genus of host-specific fungi that infect mammals via airborne particles. In humans, Pneumocystis jirovecii causes lethal infections in immunocompromised patients if untreated, although its environmental reservoir and transmission route remain unclear. Here, we attempt to clarify, by analyzing human exposome metagenomic data sets, whether humans are exposed to different Pneumocystis species present in the air but only P. jirovecii cells are able to replicate or whether they are selectively exposed to P. jirovecii Our analysis supports the latter hypothesis, which is consistent with a local transmission model. These data also suggest that healthy carriers are a major driver for the transmission.

| S-EPMC7064776 | biostudies-literature

Pneumocystis jirovecii Rtt109, a novel drug target for Pneumocystis pneumonia in immunosuppressed humans.

Project description:Pneumocystis pneumonia (PcP) is a significant cause of morbidity and mortality in immunocompromised patients. In humans, PcP is caused by the opportunistic fungal species Pneumocystis jirovecii. Progress in Pneumocystis research has been hampered by a lack of viable in vitro culture methods, which limits laboratory access to human-derived organisms for drug testing. Consequently, most basic drug discovery research for P. jirovecii is performed using related surrogate organisms such as Pneumocystis carinii, which is derived from immunosuppressed rodents. While these studies provide useful insights, important questions arise about interspecies variations and the relative utility of identified anti-Pneumocystis agents against human P. jirovecii. Our recent work has identified the histone acetyltransferase (HAT) Rtt109 in P. carinii (i.e., PcRtt109) as a potential therapeutic target for PcP, since Rtt109 HATs are widely conserved in fungi but are absent in humans. To further address the potential utility of this target in human disease, we now demonstrate the presence of a functional Rtt109 orthologue in the clinically relevant fungal pathogen P. jirovecii (i.e., PjRtt109). In a fashion similar to that of Pcrtt109, Pjrtt109 restores H3K56 acetylation and genotoxic resistance in rtt109-null yeast. Recombinant PjRtt109 is an active HAT in vitro, with activity comparable to that of PcRtt109 and yeast Rtt109. PjRtt109 HAT activity is also enhanced by the histone chaperone Asf1 in vitro. PjRtt109 and PcRtt109 showed similar low micromolar sensitivities to two reported small-molecule HAT inhibitors in vitro. Together, these results demonstrate that PjRtt109 is a functional Rtt109 HAT, and they support the development of anti-Pneumocystis agents directed at Rtt109-catalyzed histone acetylation as a novel therapeutic target for human PcP.

| S-EPMC4068529 | biostudies-literature

Designing a Recombinant Multi-Epitope Antigen of <i>Echinococcus granulosus</i> to Diagnose Human Cystic Echinococcosis.

Project description:BackgroundCystic echinococcosis can cause severe disease and probable death in humans. Epitopes of its antigens play a key role in the sensitivity and specificity of immunodiagnostic tests.MethodsEpitope prediction software programs predict the most antigenic linear B-cell epitopes of AgB (8 kD), Ag5, and Ag95. Six such epitopes were predicted and connected by "Gly-Ser" linker and synthesized. The purity of the concentrated recombinant multi-epitope protein was assessed by 15% SDS-PAGE. Overall, 186 serum samples were collected from the Loghman Hakim Hospital and different laboratories, Tehran, Iran, from July 2016 to February 2017. Patients infected with hepatic hydatid cysts, patients infected by other parasites and viruses, and healthy individuals were used to detect the anti-CE IgG using recombinant multi-epitope protein.ResultsForty-one samples out of 43 cases of hydatidosis were diagnosed correctly as positive, and two were negative. In addition, six negative cases of healthy individual group were diagnosed as positive and negative with rMEP-ELISA and the commercial kit, respectively. Therefore, these six samples were considered as false positive using our method. In addition, a diagnostic sensitivity of 95.3% (95% CI, 84.19% to 99.43%) and a specificity of 95.0% (95% CI, 89.43% to 98.14%) were obtained using optimum cutoff value (0.20). The sensitivity and specificity of the commercial kit was 100%.ConclusionOur findings showed high diagnostic accuracy of the ELISA test using the developed recombinant protein, which encourages the use of this recombinant multi-epitope protein for rapid serological diagnosis of hydatidosis.

| S-EPMC7244849 | biostudies-literature

Isolation and characterization of a recombinant antigen of Pneumocystis carinii.

Project description:Pneumocystis carinii contains a major group of antigens which migrates as a broad band of 45 to 55 kDa and 35 to 45 kDa in organisms derived from rats and humans, respectively. This complex is among the most common P. carinii antigens found in the respiratory tract and is recognized by serum antibodies of infected individuals. We have isolated a cDNA clone encoding the 3' portion of a 45- to 55-kDa antigen of rat-derived P. carinii. The predicted protein encoded by this cDNA contains a distinctive domain composed of 10 copies of a 7-amino-acid sequence motif rich in glutamic acid residues. Affinity-purified antibodies to this peptide reacted with the 45- to 55-kDa band of rat-derived P. carinii and with the 35- to 45-kDa band of human-derived P. carinii, indicating shared epitopes. The fusion protein was recognized by serum antibodies from rats and humans with natural exposure to P. carinii and by human immunodeficiency virus patients with P. carinii pneumonia. The production of this recombinant protein should allow more detailed studies of the host-parasite relationship of this important opportunistic infection.

| S-EPMC257572 | biostudies-other

Active immunization against Pneumocystis carinii with a recombinant P. carinii antigen.

Project description:Mice immunized with recombinant mouse Pneumocystis carinii antigen A12-thioredoxin fusion protein developed an antibody response that recognized P. carinii antigens, as determined by Western blotting and immunofluorescence analysis. Compared to mice immunized with thioredoxin alone, mice immunized with A12-thioredoxin had significantly reduced lung P. carinii burdens after CD4+ T-cell depletion and challenge with P. carinii.

| S-EPMC1418926 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data