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1.
Zhonghua Nei Ke Za Zhi ; 58(11): 826-828, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31665859

RESUMO

This study aims to explore the diagnostic value of specific immunoglobulin E (sIgE) and specific immunoglobulin G (sIgG) of Aspergillus fumigatus in the diagnosis of allergic broncho-pulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). A total of 17 ABPA patients and 14 SAFS patients were enrolled. The levels of sIgG [2 294.00 (1 527.00, 14 170.00) U/ml vs. 972.60 (650.90, 1 792.00) U/ml] and sIgE [8.77 (1.64, 16.85) kU/L vs. 1.04 (0.70, 2.05) kU/L] in ABPA patients were significantly higher than those in SAFS patients (P<0.05). Aspergillus fumigatus sIgG was strongly correlated with Aspergillus fumigatus sIgE (r(s)=0.797, P<0.001) in ABPA patients. When combined with Aspergillus fumigatus sIgG (>1 000.00 U/mL) and Aspergillus fumigatus sIgE (>1.00 kU/L), the sensitivity was 82.3% and specificity 78.6% for the differential diagnosis of ABPA and SAFS. It demonstrates the diagnostic value of Aspergillus fumigatus sIgG and sIgE.


Assuntos
Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Asma/complicações , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Anticorpos Antifúngicos/imunologia , Aspergilose Broncopulmonar Alérgica/sangue , Aspergilose Broncopulmonar Alérgica/imunologia , Aspergilose Broncopulmonar Alérgica/microbiologia , Aspergillus fumigatus/imunologia , Asma/sangue , Asma/diagnóstico , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Índice de Gravidade de Doença
2.
Artigo em Inglês | MEDLINE | ID: mdl-31380292

RESUMO

Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA). Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients. However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides. More specific antibodies are therefore needed. Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen. The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species. Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium. The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope. Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins. Glycoarray analysis revealed that AP3 recognizes oligo-[ß-D-Galf-1,5] sequences containing four or more residues with longer chains more efficiently. We also showed that AP3 captures GM in serum, suggesting it may be useful as a diagnostic tool for patients with IA.


Assuntos
Anticorpos Antifúngicos/imunologia , Anticorpos Monoclonais/imunologia , Antígenos de Fungos/imunologia , Aspergilose/imunologia , Aspergillus/imunologia , Mananas/imunologia , Animais , Antígenos de Fungos/genética , Aspergillus/genética , Aspergillus flavus/genética , Aspergillus flavus/imunologia , Aspergillus fumigatus/imunologia , Parede Celular/química , Reações Cruzadas , Modelos Animais de Doenças , Epitopos/isolamento & purificação , Feminino , Testes Imunológicos , Mananas/genética , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos Bacterianos/imunologia , Proteínas Recombinantes
3.
Future Microbiol ; 14: 867-884, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31340660

RESUMO

Aim: Cryptococcus neoformans is the major agent of cryptococcosis. The main virulence factor is the polysaccharide (PS) capsule. Changes in cryptococcal PS properties have been poorly elucidated. Materials & methods: We analyzed the mechanical properties of secreted PS and intact capsules, using dynamic light scattering and optical tweezers. Results: Storage and loss moduli showed that secreted PS behaves as a viscoelastic liquid, while capsular PS behaves as a viscoelastic solid. The secreted PS remains as a viscoelastic fluid at different temperatures with thermal hysteresis after 85°C. Antibody binding altered the viscoelastic behavior of both secreted and capsular PS. Conclusion: Deciphering the mechanical aspects of these structures could reveal features that may have consequences in novel therapies against cryptococcosis.


Assuntos
Anticorpos Antifúngicos/metabolismo , Cryptococcus neoformans/química , Polissacarídeos/fisiologia , Temperatura , Fatores de Virulência/fisiologia , Anticorpos Antifúngicos/imunologia , Cápsulas Fúngicas/química , Cápsulas Fúngicas/imunologia , Cápsulas Fúngicas/fisiologia , Pinças Ópticas , Tamanho da Partícula , Polissacarídeos/química , Polissacarídeos/imunologia , Polissacarídeos/metabolismo , Reologia , Fatores de Virulência/química , Fatores de Virulência/imunologia , Fatores de Virulência/metabolismo , Substâncias Viscoelásticas
4.
Mycopathologia ; 184(3): 393-402, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31201650

RESUMO

Recently, we have reported serological cross-reactivity between paracoccidioidomycosis ceti and paracoccidioidomycosis, histoplasmosis, and coccidioidomycosis. However, data on the interaction of Arthrographis kalrae with the above pathogenic fungal infections are lacking. A. kalrae is a widely occurring ascomycetous fungus; causes superficial and deep mycoses; shows thermally dependent dimorphism; and has a genomic profile related to the above-mentioned fungal species. Our study aims to investigate cross-reactivity using eight murine sera, obtained from experimental infection with two A. kalrae isolates. The murine sera were incubated with fungal cells of A. kalrae, Coccidioides posadasii, Histoplasma capsulatum, Paracoccidioides sp., and P. brasiliensis. Thirty murine sera, obtained from experimental infection with six isolates of H. capsulatum, sera from three cases of dolphin paracoccidioidomycosis ceti, two human sera from patients with paracoccidioidomycosis, and a serum sample from a healthy person with a history of coccidioidomycosis, were also incubated with A. kalrae fungal cells and the respective fungal cells that caused the infection as positive controls. Sera derived from the mice infected with A. kalrae reacted strongly when incubated with the Paracoccidioides sp., P. brasiliensis, and C. posadasii, but no positive reaction was observed against the fungal cells of H. capsulatum. The murine sera infected with three out of six isolates of H. capsulatum, and all cetacean and human serum samples reacted positively with the fungal cells of A. kalrae. The present study demonstrated serological cross-reactions among A. kalrae infection, coccidioidomycosis, paracoccidioidomycosis, paracoccidioidomycosis ceti, and histoplasmosis.


Assuntos
Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Antígenos de Fungos/imunologia , Ascomicetos/imunologia , Reações Cruzadas , Animais , Golfinhos , Humanos , Camundongos
5.
mSphere ; 4(3)2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167944

RESUMO

Rhodotorula yeasts are pink, encapsulated basidiomycetes isolated from a variety of environments and clinical settings. They are increasingly linked with disease, particularly central venous catheter infections and meningitis, in immunocompromised patients. Eight clinical and eight environmental strains molecularly typed as Rhodotorula mucilaginosa were compared to six Cryptococcus neoformans strains for phenotypic variability. Growth on cell integrity-challenging media suggested that R. mucilaginosa cells possess differences in signaling pathways, cell wall composition, or assembly and that their membranes are more susceptible to perturbations than those of C. neoformans All 16 R. mucilaginosa strains produced urease, while none produced melanin with l-3,4-dihydroxyphenylalanine (l-DOPA) as a substrate. India ink staining reveals that clinical R. mucilaginosa capsules are larger than environmental capsules but that both are generally smaller than C. neoformans capsules. All R. mucilaginosa strains were resistant to fluconazole. Only two clinical strains were susceptible to voriconazole; all of the environmental strains were resistant. We generated an anticapsular antibody (Rh1) to R. mucilaginosa; Rh1 did not bind C. neoformans control strains, was specific to Rhodotorula species, and bound to all tested Rhodotorula strains. Binding assays performed with wheat germ agglutinin (WGA), concanavalin A (ConA), calcofluor white (CFW), and eosin Y dye (EY) cell surface probes suggested that chitin may be more accessible in R. mucilaginosa but that the total abundance of chitooligomers is less than in C. neoformans This report describes a novel reagent that can be used to identify Rhodotorula species and lays the foundation for future cell envelope composition analysis.IMPORTANCE Currently, there is very little known about the phenotypic variability within species of Rhodotorula strains and the role of their capsule. Cryptococcus neoformans has been considered the only encapsulated human fungal pathogen, but as more individuals come to live in states of immunocompromised health, they are more susceptible to fungal infections, including those by Rhodotorula R. mucilaginosa species are some of those most commonly associated with clinical infections. We wanted to know if clinical and environmental strains of R. mucilaginosa demonstrated disparate capsule phenotypes. With limited antifungal options available and clinical Rhodotorula spp. often resistant to common antifungal drugs such as fluconazole, caspofungin (1, 2), and voriconazole (2), a better understanding of the fungal biology could inform the design and use of future antifungal drugs. The generation of an antibody specific to Rhodotorula fungi could be a useful diagnostic tool, and this work presents the first mention of such in the literature.


Assuntos
Parede Celular/química , Cápsulas Fúngicas/química , Rhodotorula/química , Animais , Anticorpos Antifúngicos/imunologia , Antifúngicos/farmacologia , Parede Celular/efeitos dos fármacos , Cryptococcus neoformans/química , Cryptococcus neoformans/efeitos dos fármacos , Cápsulas Fúngicas/efeitos dos fármacos , Humanos , Melaninas , Fenótipo , Coelhos , Rhodotorula/efeitos dos fármacos , Transdução de Sinais , Urease/biossíntese
6.
Intern Med ; 58(19): 2835-2838, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243216

RESUMO

Allergic bronchopulmonary aspergillosis (ABPA) is an eosinophilic inflammatory condition characterized by exaggerated immune responses to the fungal genus Aspergillus. Pulmonary manifestations in patients with Crohn's disease (CD) are frequent comorbidities. A 66-year-old man with CD treated with an anti-tumor necrosis factor-α antibody presented with dyspnea. Laboratory findings of elevated blood eosinophils and total serum IgE and positive aspergillus-specific antibodies as well as imaging findings of central bronchiectasis and mucoid impaction indicated a diagnosis of ABPA. To our knowledge, this is the first report of ABPA arising in a patient with CD. We discuss the pathophysiological mechanism of this rare complication.


Assuntos
Aspergilose Broncopulmonar Alérgica/etiologia , Doença de Crohn/complicações , Pulmão/diagnóstico por imagem , Idoso , Anticorpos Antifúngicos/imunologia , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/microbiologia , Aspergillus/imunologia , Eosinófilos/patologia , Humanos , Imunoglobulina E/imunologia , Pulmão/fisiopatologia , Masculino , Radiografia Torácica , Tomografia Computadorizada por Raios X
7.
J Immunol ; 202(10): 2945-2956, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988115

RESUMO

Imprime PGG (Imprime) is an i.v. administered, yeast ß-1,3/1,6 glucan in clinical development with checkpoint inhibitors. Imprime-mediated innate immune activation requires immune complex formation with naturally occurring IgG anti-ß glucan Abs (ABA). We administered Imprime to healthy human volunteers to assess the necessity of ABA for Imprime-mediated immunopharmacodynamic (IPD) changes. Imprime (4 mg/kg) was administered i.v. in single and multiple infusions. Subsets of subjects were premedicated with antihistamine and corticosteroid. Peripheral blood was measured before, during and after Imprime administration for IPD changes (e.g., ABA, circulating immune complexes, complement activation, complete blood counts, cytokine/chemokine, and gene expression changes). IPD changes were analyzed based on pretreatment serum ABA levels: low-ABA (<20 µg/ml), mid-ABA (≥20-50 µg/ml), and high-ABA (≥50 µg/ml). At the end of infusion, free serum ABA levels decreased, circulating immune complex levels increased, and complement activation was observed. At ∼1-4 h after end of infusion, increased expression of cytokines/chemokines, a 1.5-4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed. Low-ABA subjects typically showed minimal IPD changes except when ABA levels rose above 20 µg/ml after repeated Imprime dosing. Mild-to-moderate infusion-related reactions occurred in subjects with ABA ≥20 µg/ml. Premedications alleviated some of the infusion-related reactions, but also inhibited cytokine responses. In conclusion, ABA levels, being critical for Imprime-mediated immune activation may provide a plausible, mechanism-based biomarker to identify patients most likely to respond to Imprime-based anticancer immunotherapy.


Assuntos
Adjuvantes Imunológicos , Polissacarídeos Fúngicos , Imunoterapia , Neoplasias , Saccharomyces cerevisiae/química , beta-Glucanas , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacocinética , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Quimiocinas/sangue , Quimiocinas/imunologia , Feminino , Polissacarídeos Fúngicos/administração & dosagem , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacocinética , Humanos , Masculino , Neoplasias/sangue , Neoplasias/imunologia , Neoplasias/terapia , beta-Glucanas/administração & dosagem , beta-Glucanas/química , beta-Glucanas/farmacocinética
9.
Infect Immun ; 87(4)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30670549

RESUMO

Disseminated infections with the fungal species Cryptococcus neoformans or, less frequently, Cryptococcus gattii are an important cause of mortality in immunocompromised individuals. Central to the virulence of both species is an elaborate polysaccharide capsule that consists predominantly of glucuronoxylomannan (GXM). Due to its abundance, GXM is an ideal target for host antibodies, and several monoclonal antibodies (mAbs) have previously been derived using purified GXM or whole capsular preparations as antigens. In addition to their application in the diagnosis of cryptococcosis, anti-GXM mAbs are invaluable tools for studying capsule structure. In this study, we report the production and characterization of a novel anti-GXM mAb, Crp127, that unexpectedly reveals a role for GXM remodeling during the process of fungal titanization. We show that Crp127 recognizes a GXM epitope in an O-acetylation-dependent, but xylosylation-independent, manner. The epitope is differentially expressed by the four main serotypes of Cryptococcus neoformans and C. gattii, is heterogeneously expressed within clonal populations of C. gattii serotype B strains, and is typically confined to the central region of the enlarged capsule. Uniquely, however, this epitope redistributes to the capsular surface in titan cells, a recently characterized morphotype where haploid 5-µm cells convert to highly polyploid cells of >10 µm with distinct but poorly understood capsular characteristics. Titan cells are produced in the host lung and critical for successful infection. Crp127 therefore advances our understanding of cryptococcal morphological change and may hold significant potential as a tool to differentially identify cryptococcal strains and subtypes.


Assuntos
Criptococose/microbiologia , Cryptococcus neoformans/crescimento & desenvolvimento , Cryptococcus neoformans/imunologia , Epitopos/imunologia , Polissacarídeos/imunologia , Animais , Anticorpos Antifúngicos/imunologia , Criptococose/imunologia , Cryptococcus neoformans/química , Cryptococcus neoformans/patogenicidade , Humanos , Camundongos Endogâmicos BALB C , Polissacarídeos/química , Sorogrupo , Especificidade da Espécie , Virulência
10.
Artigo em Inglês | MEDLINE | ID: mdl-30117403

RESUMO

Backgraund and Objective: Anti-Saccharomyces Cerevisiae Antibodies (ASCA) that are considered to reflect immune response against increased intestinal permeability due to mucosal damage are among the serological markers of Crohn's Disease. METHODS: This microbial seromarker was recently shown to be elevated in several autoimmune disorders such as celiac disease, autoimmune liver diseases, type 1 diabetes, and Graves' disease. Despite that fact, ASCA seropositivity in Autoimmune Polyglandular Syndrome (APS) has never been reported before. RESULTS: Herein, we present a 46-year-old woman who has uveitis, autoimmune thyroiditis, and primary ovarian failure. CONCLUSION: Based on the coexistence of these diseases, the patient was diagnosed with APS type III. Moreover, ASCA seropositivity was detected although she has no overt intestinal disease.


Assuntos
Anticorpos Antifúngicos/imunologia , Poliendocrinopatias Autoimunes/imunologia , Saccharomyces cerevisiae/imunologia , Biomarcadores , Feminino , Humanos , Pessoa de Meia-Idade , Poliendocrinopatias Autoimunes/sangue
11.
Mycoses ; 62(1): 32-40, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30152879

RESUMO

BACKGROUND: Onychomycosis is the most prevalent nail disease and is mainly caused by two dermatophyte species Trichophyton rubrum and Trichophyton interdigitale with a frequency in the range of 80% and 20%, respectively. The secreted protease Sub6 of the subtilisin family, which was never detected in vitro growth conditions, was found to be a robust marker of onychomycosis. OBJECTIVE: The aim of this work was to detect tinea unguium using anti-Sub6 monoclonal antibodies in proteins extracted from clinical nail samples. METHODS: We produced monoclonal antibodies in mice using recombinant Sub6 as an antigen. Selected monoclonal antibodies were tested by Western blot analysis and ELISA on protein extracts from onychomycosis samples. RESULTS: Several monoclonal antibodies used to quantify Sub6 in proteins extracted from clinical nail samples were produced and characterised. We showed that these antibodies were very specific and allowed the detection of T. rubrum and T. interdigitale in onychomycosis. Sub6 was detected in clinical samples infected by T. rubrum and not detected in nails with trauma and other diseases. CONCLUSION: Anti-Sub6 monoclonal antibodies could be useful for a rapid diagnosis of tinea unguium and/or therapeutic survey of dermatophyte in onychomycosis by ELISA or an immunochromatography device such as a strip test.


Assuntos
Anticorpos Antifúngicos/imunologia , Anticorpos Monoclonais/imunologia , Antígenos de Fungos/análise , Imunoensaio/métodos , Onicomicose/diagnóstico , Onicomicose/microbiologia , Trichophyton/isolamento & purificação , Animais , Western Blotting/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Camundongos , Peptídeo Hidrolases/análise , Sensibilidade e Especificidade
12.
Am J Physiol Lung Cell Mol Physiol ; 316(1): L291-L301, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30284926

RESUMO

Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells play an important role in infectious diseases. In the present study, the immune regulatory role of mature B cells in host defense to Pneumocystis was evaluated. Pneumocystis infection resulted in a decrease in B cells in patients and mice, and the Pneumocystis burden in B cell-deficient mice also progressively increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was delayed in B cell-activating factor receptor (BAFF-R)-deficient mice (BAFF-R-/- mice), which had few B cells and Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild-type (WT) mice. There were fewer effector CD4+ T cells and higher percentages of T helper (Th)1/Th17 cells in BAFF-R-/- mice than in WT mice. Adoptive transfer of naive B cells, mRNA sequencing, and IL-1ß neutralization experiments indicated that IL-1ß is a likely determinant of the IL-10-producing B cell-mediated suppression of Th1/Th17-cell immune responses in BAFF-R-/- PCP mice. Our data indicated that B cells play a vital role in the regulation of Th cells in response to Pneumocystis infection.


Assuntos
Linfócitos B/imunologia , Interleucina-10/imunologia , Pneumocystis/imunologia , Pneumonia por Pneumocystis/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adulto , Animais , Anticorpos Antifúngicos/imunologia , Receptor do Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/imunologia , Linfócitos B/patologia , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Interleucina-10/genética , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Masculino , Camundongos , Camundongos Knockout , Pneumonia por Pneumocystis/genética , Pneumonia por Pneumocystis/patologia , Células Th1/patologia , Células Th2/patologia
13.
Inflamm Bowel Dis ; 25(2): 336-344, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30265311

RESUMO

Background: We evaluated the impact of variations in ATG16L1 and NOD2 and genes on serologic responses in patients with inflammatory bowel disease (IBD). Methods: We recruited 308 IBD patients: 130 with Crohn's disease (CD), 67 with ulcerative colitis (UC), 111 with UC and an ileal pouch (UC-pouch), and 74 healthy controls. NOD2 variants (1007fs, G908R, R702W) and the ATG16L1 A300T variant were analyzed. The antiglycan antibodies anti-Saccharomyces cerevisiae (ASCA), antilaminaribioside (ALCA), antichitobioside (ACCA), and antimannobioside carbohydrate (AMCA) were analyzed by enzyme-linked immunosorbent assay. Results: Antichitobioside was positive in 28% of patients with CD carrying the ATG16L1 A300T variant (either heterozygote or homozygote) compared with only 3% in those without the variant (P < 0.001). Anti-Saccharomyces cerevisiae was positive in 86% of patients with CD carrying the NOD2 1007fs variant compared with 36% in those without the variant (P < 0.001). UC-pouch patients with the NOD2 1007fs variant had elevated ASCA and ALCA levels compared with those without the variant (50% vs 7%, P = 0.004, and 50% vs 8%, P = 0.006, respectively). Importantly, ATG16L1 A300T and NOD2 variants were not associated with serologic responses in healthy controls and unoperated UC patients. Multivariate analysis demonstrated that these genetic variants are the main factors associated with specific antiglycan antibody levels in CD and pouch patients. Conclusions: Genetic variants may have disease-specific phenotypic (serotypic) effects. This implies that genetic risk factors may also be disease modifiers.


Assuntos
Anticorpos/sangue , Proteínas Relacionadas à Autofagia/genética , Biomarcadores/análise , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Mutação , Proteína Adaptadora de Sinalização NOD2/genética , Anticorpos/imunologia , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Estudos de Casos e Controles , Estudos Transversais , Seguimentos , Genótipo , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/epidemiologia , Fenótipo , Polissacarídeos/imunologia , Prognóstico , Saccharomyces cerevisiae/imunologia , Sorogrupo
15.
Nat Commun ; 9(1): 5288, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30538246

RESUMO

The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations. Antibody genes from Candida-reactive B cell cultures were cloned and expressed in Expi293F human embryonic kidney cells to generate a panel of human recombinant anti-Candida mAbs that demonstrate morphology-specific, high avidity binding to the cell wall. The species-specific and pan-Candida mAbs generated through this technology display favourable properties for diagnostics, strong opsono-phagocytic activity of macrophages in vitro, and protection in a murine model of disseminated candidiasis.


Assuntos
Anticorpos Antifúngicos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Linfócitos B/imunologia , Candida albicans/fisiologia , Candidíase/imunologia , Candidíase/prevenção & controle , Fagocitose , Animais , Anticorpos Antifúngicos/genética , Anticorpos Antifúngicos/imunologia , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Candida , Candida albicans/efeitos dos fármacos , Candidíase/microbiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C
16.
Allergol. immunopatol ; 46(6): 557-564, nov.-dic. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-177895

RESUMO

Introduction and objectives: Although the prevalence of sensitization to fungi is not precisely known, it can reach 50% in inner cities and has been identified as a risk factor in the development of asthma. Whereas the prevalence of allergic diseases is increasing, it is unclear whether the same occurs with sensitization to fungi. Patients and methods: A retrospective study was performed at the "Hospital Infantil de México Federico Gómez". From skin tests taken between 2004 and 2015, information was gathered about Alternaria alternata, Aspergillus fumigatus, Candida albicans, Cladosporium herbarum, Mucor mucedo and Penicillium notatum. The participating patients were 2-18 years old, presented some type of allergic condition, and underwent immediate hypersensitivity tests to the fungi herein examined. Descriptive analysis and chi-squared distribution were used. Results: Of the 8794 patients included in the study, 14% showed a negative result to the entire panel of environmental allergens. The remaining 7565 individuals displayed sensitization to at least one fungus, which most frequently was Aspergillus, with a rate of 16.8%. When the patients were divided into age groups, the same trend was observed. The highest percentage of sensitization (58%) toward at least one type of fungus was found in 2014, and the lowest percentage (49.8%) in 2008. Conclusion: The rate of sensitization to at least one type of fungus was presently over 50%, higher than that detected in other medical centers in Mexico. This rate was constant over the 11-year study, and Aspergillus exhibited the greatest frequency of sensitization among the patients


No disponible


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Alérgenos/imunologia , Anticorpos Antifúngicos/imunologia , Asma/epidemiologia , Fungos/imunologia , Hipersensibilidade/epidemiologia , Imunização , México/epidemiologia , Estudos Retrospectivos , Prevalência
17.
Mycopathologia ; 183(5): 793-803, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30168080

RESUMO

Paracoccidioidomycosis ceti is a cutaneous disease of cetaceans caused by uncultivated Paracoccidioides brasiliensis or Paracoccidioides spp. Serological cross-reactions between paracoccidioidomycosis ceti and paracoccidioidomycosis, paracoccidioidomycosis and histoplasmosis, and paracoccidioidomycosis and coccidioidomycosis have been reported before. The present study aimed to detect immunohistochemical cross-reaction between antibodies to Paracoccidioides sp. and Histoplasma capsulatum, and vice versa. Thirty murine sera, obtained from experimental infections of 6 isolates of H. capsulatum, were reacted with paraffin-embedded yeast-form cells of Paracoccidioides sp. derived from a case of paracoccidioidomycosis ceti in Japan. The murine sera were also reacted with human isolates of H. capsulatum yeast cells, with P. brasiliensis yeast cells, and with fungal cells of Coccidioides posadasii. Three dolphins' sera from cases of paracoccidioidomycosis ceti, two human sera from patients with paracoccidioidomycosis, and a serum from a healthy person with a history of coccidioidomycosis were used in order to determine that the tested fungal cells reacted properly. Sera derived from mice infected with an isolate of H. capsulatum reacted positively against yeast cells of Paracoccidioides sp., yeast cells of P. brasiliensis, and fungal cells of C. posadasii, while those derived from other strains were negative. The present study recorded for the first time the cross-reaction between the yeast cells of H. capsulatum and antibodies against Paracoccidioides spp., the yeast cells of Paracoccidioides sp. and antibodies against H. capsulatum, the yeast cells of Paracoccidioides sp. and antibodies against Coccidioides sp., and fungal cells of C. posadasii and antibodies against Paracoccidioides spp.


Assuntos
Anticorpos Antifúngicos/imunologia , Reações Cruzadas , Histoplasma/imunologia , Imuno-Histoquímica , Paracoccidioides/imunologia , Paracoccidioidomicose/veterinária , Animais , Golfinhos , Humanos , Camundongos , Paracoccidioidomicose/imunologia
18.
PLoS One ; 13(8): e0202804, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30157221

RESUMO

The sensitivity of the double agar gel immunodiffusion test is about 90% in patients with untreated paracoccidioidomycosis (PCM), but it is much lower in cases of relapse. In addition, serum from patients with PCM caused by Paracoccidioides lutzii, frequent in the Midwest region of Brazil, do not react with the classical antigen obtained from Pb B-339. These findings showed the need for alternative diagnostic methods, such as biological markers through proteomics. The aim of this study was to identify biomarkers for the safe identification of PCM relapse and specific proteins that could distinguish infections caused by Paracoccidioides brasiliensis from those produced by Paracoccidioides lutzii. Proteomic analysis was performed in serum from 9 patients with PCM caused by P. brasiliensis, with and without relapse, from 4 patients with PCM produced by P. lutzii, and from 3 healthy controls. The comparative evaluation of the 29 identified plasma proteins suggested that the presence of the immunoglobulin (Ig) alpha-2 chain C region and the absence of Ig heavy chain V-III TIL indicate infection by P. lutzii. In addition, the absence of complement factor B protein might be a predictor of relapse. The evaluation of these proteins in a higher number of patients should be carried out in order to validate these findings.


Assuntos
Biomarcadores/sangue , Paracoccidioides/metabolismo , Paracoccidioidomicose/diagnóstico , Proteômica , Adolescente , Adulto , Idoso de 80 Anos ou mais , Anticorpos Antifúngicos/química , Anticorpos Antifúngicos/imunologia , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Proteínas Fúngicas/análise , Proteínas Fúngicas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Paracoccidioides/isolamento & purificação , Paracoccidioidomicose/microbiologia , Recidiva , Risco , Espectrometria de Massas em Tandem
19.
Sensors (Basel) ; 18(7)2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-29996525

RESUMO

Candidemia and invasive candidiasis is a cause of high mortality and morbidity rates among hospitalized patients worldwide. The occurrence of the infections increases due to the complexity of the patients and overuse of the antifungal therapy. The current Candida detection method includes blood culturing which is a lengthy procedure and thus delays the administration of the antifungal therapy. Even though the results are available after 48 h it is still the gold standard in pathogen detection in a hospital setting. In this work we present an electrochemical impedance sensor that is capable of detecting Candida albicans yeast. The yeast cells are captured on electrodes specifically functionalized with anti-Candida antibodies and detection is achieved by electrochemical impedance spectroscopy. The sensor allows for detection of the yeast cells at clinically relevant concentrations in less than 1 h.


Assuntos
Candida albicans/isolamento & purificação , Espectroscopia Dielétrica/instrumentação , Anticorpos Antifúngicos/imunologia , Candida albicans/imunologia , Candidemia/sangue , Candidemia/diagnóstico , Candidemia/microbiologia , Candidíase/sangue , Candidíase/diagnóstico , Candidíase/microbiologia , Eletrodos , Humanos , Fatores de Tempo
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