Dataset Information

Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins.

ABSTRACT: American tegumentary leishmaniasis (TL) caused by Leishmania braziliensis is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of Leishmania-specific anti-α-Gal antibodies. However, the native parasite α-Gal glycotope(s) is(are) still elusive, thus they have not yet been explored for a more accurate TL diagnosis. Using a chemiluminescent immunoassay, we evaluated the seroreactivity of TL patients across its clinical spectrum, and of endemic (EC) and nonendemic healthy controls (NEC) against three synthetic neoglycoproteins (NGP29b, NGP30b, and NGP28b), respectively comprising the L. major-derived type-2 glycoinositolphospholipid (GIPL)-1 (Galfβ1,3Manα), GIPL-2 (Galα1,3Galfβ1,3Manα), and GIPL-3 (Galα1,6Galα1,3Galfβ) glycotopes. Contrary to NGP29b and NGP30b, NGP28b exhibited high sensitivity and specificity to a CL serum pool. More importantly, NGP28b reacted strongly and specifically with individual sera from distinct clinical forms of TL, especially with SC sera, with 94% sensitivity and 97% specificity, by post-two-graph receiver-operating characteristic curve analysis. Contrary to NGP29b, NGP28b showed low cross-reactivity with Chagas disease and control (NEC/EC) sera. Additionally, seroreactivity of CL patients against NGP28b was significantly decreased after successful chemotherapy, indicating that L. braziliensis-specific anti-α-Gal antibodies may serve as an early biomarker of cure in CL. Our data also points towards the applicability of L. major type-2 GIPL-3-derived Galα1,6Galα1,3Galfβ glycotope for the serological diagnosis of American TL, particularly of the subclinical form.

SUBMITTER: Viana SM

PROVIDER: S-EPMC9518598 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins.

Viana Sayonara M SM Montoya Alba L AL Carvalho Augusto M AM de Mendonça Brunele S BS Portillo Susana S Olivas Janet J JJ Karimi Nasim H NH Estevao Igor L IL Ortega-Rodriguez Uriel U Carvalho Edgar M EM Dutra Walderez O WO Maldonaldo Rosa A RA Michael Katja K de Oliveira Camila I CI Almeida Igor C IC

Emerging microbes & infections 20221201 1

American tegumentary leishmaniasis (TL) caused by <i>Leishmania braziliensis</i> is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of <i>Leishmania</i>-specific anti-α-Gal antibodies. Howev ...[more]

PMID: 36039908

Similar Datasets

Project description:BackgroundTegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by Leishmania parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.Methodology and principal findingsThis review focuses on the frequency of TL coinfections in human populations, interactions between Leishmania and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of Trypanosoma cruzi coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., Leishmania and Sporothrix schenckii), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.Conclusions and significanceIn patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.

Project description:BackgroundTegumentary leishmaniasis (TL) is a parasitic disease that can present a cutaneous or mucocutaneous clinical form (CL and MCL, respectively). The disease is caused by different Leishmania species and transmitted by phlebotomine sand flies. Bolivia has one of the highest incidences of the disease in South America and the diagnosis is done by parasitological techniques. Our aim was to describe the clinical and immunological characteristics of CL and MCL patients attending the leishmaniasis reference center in Cochabamba, Bolivia, in order to gain updated clinical and epidemiological information, to evaluate the diagnostic methods used and to identify biomarkers related to clinical disease and its evolution.Methodology/principal findingsThe study was conducted from September 2014 to November 2015 and 135 patients with lesions compatible with CL or MCL were included. Epidemiological and clinical data were collected using a semi-structured questionnaire. Two parasitological diagnostic methods were used: Giemsa-stained smears and culture of lesion aspirates. Blood samples obtained from participants were used to measure the concentrations of different cytokines. 59.2% (80/135) were leishmaniasis confirmed cases (CL: 71.3%; MCL: 28.7%). Sixty percent of the confirmed cases were positive by smears and 90.6% were positive by culture. 53.8% were primo-infections. Eotaxin and monokine induced by IFN-γ presented higher serum concentrations in the MCL clinical presentation compared to CL cases and no-cases. None of the cytokines presented different concentrations between primo-infections and secondary infections due to treatment failure.Conclusions/significanceIn Bolivia, parasitological diagnosis remains the reference standard in diagnosis of leishmaniasis because of its high specificity, whereas the sensitivity varies over a wide range leading to loss of cases. Until more accurate tools are implemented, all patients should be tested by both smears and culture of lesion aspirates to minimize the risk of false negatives. Our results showed higher concentrations of several cytokines in MCL compared to CL, but no differences were observed between CL and no-cases. In addition, none of the cytokines differed between primary and secondary infections. These results highlight the need of further research to identify biomarkers of susceptibility and disease progression, in addition to looking at the local cellular immune responses in the lesions.

Project description:BackgroundThe vitamin D pathway contributes to the microbicidal activity of macrophages against Leishmania infection. In addition to induction of this pathway, interferon-gamma (IFNγ), interleukin (IL)-15, and IL32γ are part of a network of pro-inflammatory cytokines. The aim of this study was to evaluate single-nucleotide polymorphisms (SNPs) in the components of the vitamin D pathway and associated cytokine genes that could be related to resistance or susceptibility to American tegumentary leishmaniasis (ATL).MethodsThe expressions of IFNG, IL15, IL32, CYP27B1, VDR, and other pro-inflammatory cytokines TNF, IL6, and IL17 genes were evaluated using real-time polymerase chain reaction (qPCR) in lesions of patients with localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). SNP genotypes/alleles (in IL15, IL32, CYP27B1, and VDR) were evaluated by TaqMan PCR assays using DNA from the blood of patients and healthy individuals. Serum vitamin D levels were determined by chemiluminescence.ResultsVitamin D pathway-associated genes were expressed in cutaneous as well as mucosal lesions. IFNG, IL6, and IL17 were more highly expressed in ML than in LCL. In contrast, IL32γ/CYP27B1/VDR mRNAs were mainly correlated in LCL, and IL32γ in ML makes strong connections with all cytokines. The SNP IL32 rs1555001 was less frequent in patients with ML. In addition, some SNPs appear to influence the VDR and CYP27B1 (IL15 rs10519613 and IL15 rs3775597) and IL6 (VDR rs7975232) expressions in LCL and the IL17 expression in ML (IL15 rs3775597). Gene expression was also correlated with clinical parameters, such as number of lesions (CYP27B1 mRNA) and treatment failure (VDR mRNA). In addition, one SNP was associated with treatment failure in ML (VDR rs7975232).ConclusionsOur findings suggested that some SNPs in the vitamin D pathway-associated genes can be related to resistance and therapeutic outcomes of ATL. They are promising candidates that need to be further evaluated to understand their biological effects in the control or immunopathogenesis of ATL.

Dataset Information

Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins.

Publications

Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets