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1.
Sci Transl Med ; 16(754): eadl3848, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959329

RESUMO

Autoantibodies to nuclear antigens are hallmarks of systemic lupus erythematosus (SLE) where they contribute to pathogenesis. However, there remains a gap in our knowledge regarding how different isotypes of autoantibodies contribute to this autoimmune disease, including the production of the critical type I interferon (IFN) cytokines by plasmacytoid dendritic cells (pDCs) in response to immune complexes (ICs). We focused on IgA, which is the second-most prevalent isotype in serum and, along with IgG, is deposited in glomeruli in individuals with lupus nephritis. We show that individuals with SLE have serum IgA autoantibodies against most nuclear antigens, correlating with IgG against the same antigen. We investigated whether IgA autoantibodies against a major SLE autoantigen, Smith ribonucleoprotein (Sm/RNP), played a role in IC activation of pDCs. We found that pDCs expressed the IgA-specific Fc receptor, FcαR, and IgA1 autoantibodies synergized with IgG in RNA-containing ICs to generate robust primary blood pDC IFN-α responses in vitro. pDC responses to these ICs required both FcαR and FcγRIIa, showing synergy between these Fc receptors. Sm/RNP IC binding to and internalization by pDCs were greater when ICs contained both IgA1 and IgG. Circulating pDCs from individuals with SLE had higher binding of IgA1-containing ICs and higher expression of FcαR than pDCs from healthy control individuals. Although pDC FcαR expression correlated with the blood IFN-stimulated gene signature in SLE, Toll-like receptor 7 agonists, but not IFN-α, up-regulated pDC FcαR expression in vitro. Together, we show a mechanism by which IgA1 autoantibodies contribute to SLE pathogenesis.


Assuntos
Complexo Antígeno-Anticorpo , Autoanticorpos , Células Dendríticas , Imunoglobulina A , Imunoglobulina G , Lúpus Eritematoso Sistêmico , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Imunoglobulina A/sangue , Autoanticorpos/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Complexo Antígeno-Anticorpo/imunologia , Complexo Antígeno-Anticorpo/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/sangue , RNA/metabolismo , Feminino , Interferon-alfa/metabolismo , Adulto , Receptores Fc/metabolismo , Receptores Fc/imunologia , Receptor 7 Toll-Like/metabolismo , Masculino , Receptores de IgG/metabolismo
2.
Int J Mol Sci ; 25(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39000360

RESUMO

Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b-/-) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b-/- mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Camundongos Knockout , Animais , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Anticorpos Antinucleares , Membranas Mitocondriais/metabolismo , Células Eritroides/metabolismo , Células Eritroides/patologia , Modelos Animais de Doenças , Imunoglobulina G/metabolismo , Camundongos Endogâmicos C57BL , Baço/metabolismo , Baço/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Feminino
3.
Int J Mol Sci ; 25(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39000522

RESUMO

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies.


Assuntos
Arachis , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/diagnóstico , Hipersensibilidade a Amendoim/imunologia , Criança , Feminino , Masculino , Pré-Escolar , Arachis/imunologia , Arachis/efeitos adversos , Testes Cutâneos/métodos , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Alérgenos/imunologia , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Estudo de Prova de Conceito , Adolescente , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Antígenos de Plantas/imunologia
4.
Scand J Immunol ; 99(4): e13353, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39007994

RESUMO

Lyme borreliosis, caused by Borrelia burgdorferi sensu lato, is the most common tickborne disease. Its neuronal form, neuroborreliosis, comprises 3 to 38% of borreliosis cases in Europe. Borrelia outer surface proteins and virulence factors, OspE and BBK32, have been previously reported to help cause infection by promoting attachment to human host epithelial cells and evading complement attack. We assessed the serological responses to BBK32 and OspE in 19 individuals diagnosed with neuroborreliosis to see whether antibodies that could both target the bacteria and neutralize the virulence mechanisms on the microbial surface emerge. Results evaluate levels of total protein, IgG and the chemokine CXCL13, a determinant for B-cell recruitment during neuroinflammation, in patients' cerebrospinal fluid samples. Antibody levels against BBK32 and OspE correlated with those against VlsE, a well-characterized diagnostic serological marker of the disease. A dual serological profile of the patients was observed. K-means clustering split the cohort into two discrete groups presenting distinct serological and CNS responses. One group contained young patients with low levels of anti-BBK32 and OspE antibodies. The other group showed stronger responses, possibly following prolonged infections or reinfections. Additionally, we assessed anti-ganglioside antibodies that could cause autoimmunity or complement dysregulation but observed that they did not correlate with neuroborreliosis in our patient cohort. The dual nature of antibody responses against the virulence factors BBK32 and OspE in neuroborreliosis patients may suggest the necessity of repeated exposures for efficient immune responses. Better protection could be achieved if the virulence factors were formulated into vaccines.


Assuntos
Anticorpos Antibacterianos , Antígenos de Bactérias , Proteínas da Membrana Bacteriana Externa , Borrelia burgdorferi , Neuroborreliose de Lyme , Humanos , Neuroborreliose de Lyme/imunologia , Neuroborreliose de Lyme/sangue , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Idoso , Borrelia burgdorferi/imunologia , Antígenos de Bactérias/imunologia , Fatores de Virulência/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Quimiocina CXCL13/sangue , Quimiocina CXCL13/imunologia , Proteínas de Bactérias/imunologia , Formação de Anticorpos/imunologia
5.
Sensors (Basel) ; 24(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39001098

RESUMO

The quartz tuning fork (QTF) is a promising instrument for biosensor applications due to its advanced properties such as high sensitivity to physical quantities, cost-effectiveness, frequency stability, and high-quality factor. Nevertheless, the fork's small size and difficulty in modifying the prongs' surfaces limit its wide use in experimental research. Our study presents the development of a QTF immunosensor composed of three active layers: biocompatible natural melanin nanoparticles (MNPs), glutaraldehyde (GLU), and anti-IgG layers, for the detection of immunoglobulin G (IgG). Frequency shifts of QTFs after MNP functionalization, GLU activation, and anti-IgG immobilization were measured with an Asensis QTF F-master device. Using QTF immunosensors that had been modified under optimum conditions, the performance of QTF immunosensors for IgG detection was evaluated. Accordingly, a finite element method (FEM)-based model was produced using the COMSOL Multiphysics software program (COMSOL License No. 2102058) to simulate the effect of deposited layers on the QTF resonance frequency. The experimental results, which demonstrated shifts in frequency with each layer during QTF surface functionalization, corroborated the simulation model predictions. A modelling error of 0.05% was observed for the MNP-functionalized QTF biosensor compared to experimental findings. This study validated a simulation model that demonstrates the advantages of a simulation-based approach to optimize QTF biosensors, thereby reducing the need for extensive laboratory work.


Assuntos
Técnicas Biossensoriais , Imunoglobulina G , Melaninas , Nanopartículas , Quartzo , Imunoglobulina G/química , Imunoglobulina G/imunologia , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Nanopartículas/química , Melaninas/química , Quartzo/química , Imunoensaio/métodos , Imunoensaio/instrumentação , Simulação por Computador , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Anti-Idiotípicos/química , Humanos
6.
Int J Epidemiol ; 53(4)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-39008896

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. METHODS: A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. RESULTS: Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3-243.9); IgG: 8.6 (5.5-13.5); LF2: [67.8 (30.0-153.1), 10.9 (7.2-16.4)]); and BFRF1: 26.1 (10.1-67.5), 6.1 (2.7-13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. CONCLUSIONS: In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings.


Assuntos
Anticorpos Antivirais , Detecção Precoce de Câncer , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Imunoglobulina A , Imunoglobulina G , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , China/epidemiologia , Feminino , Pessoa de Meia-Idade , Herpesvirus Humano 4/imunologia , Estudos Prospectivos , Anticorpos Antivirais/sangue , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/epidemiologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/sangue , Adulto , Imunoglobulina A/sangue , Detecção Precoce de Câncer/métodos , Imunoglobulina G/sangue , Idoso , Estudos de Casos e Controles , Modelos de Riscos Proporcionais , População do Leste Asiático
7.
Exp Dermatol ; 33(7): e15125, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38946225

RESUMO

The 16th non-collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%-90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti-BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti-NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His-tagged proteins covering the entire BP180 ectodomain (BP180(ec)1-4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A-negative pemphigoid patients.


Assuntos
Autoanticorpos , Autoantígenos , Colágeno Tipo XVII , Esclerose Múltipla , Colágenos não Fibrilares , Doença de Parkinson , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Humanos , Doença de Parkinson/imunologia , Doença de Parkinson/sangue , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/sangue , Autoantígenos/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/sangue , Autoanticorpos/sangue , Autoanticorpos/imunologia , Penfigoide Mucomembranoso Benigno/imunologia , Penfigoide Mucomembranoso Benigno/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Epitopos/imunologia , Domínios Proteicos , Feminino , Masculino , Idoso
8.
BMJ Open ; 14(6): e084582, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950992

RESUMO

BACKGROUND: Toxoplasmosis is a zoonotic parasitic disease caused by Toxoplasma gondii (T. gondii). It has a wide host range and is capable of vertical transmission in pregnant women, which may lead to undesirable pregnancy outcomes such as congenital malformations, miscarriage, premature birth and stillbirth. This study investigated the seroprevalence of T. gondii infection among pregnant women attending the antenatal clinic at Namwala District Hospital in Southern Zambia. METHODS: This was a cross-sectional study where blood was collected, and the serum was tested for Toxoplasma IgG and IgM. A questionnaire was administered to participants on demographic characteristics and risk factors. Data were entered in Microsoft Excel and exported to STATA version 14 for analysis. RESULTS: A total of 401 women were enrolled in the study from 3 March to 5 August 2021. The seroprevalence of Toxoplasma IgG was 4.2% (n=17), while the seroprevalence of Toxoplasma IgM was 0.7% (n=3). The median age was 27 (IQR: 24-30) years, and a larger proportion had primary-level education (n=223, 55.6%). The majority (81.6%) of the women were married. None of the risk factors investigated in this study were significant for T. gondii infection. CONCLUSION: There was a low seroprevalence of T. gondii infection among pregnant women in the Namwala district of Southern Province, Zambia, and regular screening may not be warranted in this population. Continued research on toxoplasmosis is recommended to understand its epidemiology across Zambia.


Assuntos
Anticorpos Antiprotozoários , Imunoglobulina M , Complicações Parasitárias na Gravidez , Toxoplasma , Toxoplasmose , Humanos , Feminino , Zâmbia/epidemiologia , Estudos Transversais , Estudos Soroepidemiológicos , Adulto , Gravidez , Toxoplasmose/epidemiologia , Toxoplasmose/sangue , Fatores de Risco , Toxoplasma/imunologia , Adulto Jovem , Imunoglobulina M/sangue , Anticorpos Antiprotozoários/sangue , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/sangue , Imunoglobulina G/sangue , Cuidado Pré-Natal
10.
Biomed Environ Sci ; 37(6): 628-638, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38988113

RESUMO

Objective: Pertussis cases have increased markedly since 2018 in Guangxi. The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population. Method: A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay (ELISA). Results: Of the collected samples, 1,833 (17.94%) tested positive for anti-pertussis IgG, with the median concentration of 16.06 IU/mL. Antibody level < 10 IU/mL accounted for more than 60% in children under 4 years of age, but declined with age, whereas the percentages of the other three levels (10-40, 40-50, and ≥ 50 IU/mL) increased almost with age ( P < 0.001). Moreover, 7,924 samples were selected for anti-pertussis toxin IgG, of which 653 (8.24%) tested positive (≥ 40 IU/mL) with the median concentration of 5.89 IU/mL, and 204 participants (2.56%) had recent pertussis infection (≥ 100 IU/mL). Among the different age groups, the highest rates of positivity and recent infection were observed at 11-20 years of age, the lowest positivity rate at 5 years of age, and the lowest recent infection rate at 4 years of age ( P < 0.001, P = 0.005, respectively). Conclusion: The survey results showed that all age groups in Guangxi lacked immunity against pertussis, which was one of the main factors contributing to the resurgence of pertussis in 2018. In addition, the prevalence of pertussis is relatively high in Guangxi, and its incidence is seriously underestimated, especially in adolescents and adults.


Assuntos
Anticorpos Antibacterianos , Imunoglobulina G , Coqueluche , Humanos , Coqueluche/epidemiologia , Coqueluche/imunologia , Coqueluche/sangue , Pré-Escolar , Criança , China/epidemiologia , Adolescente , Adulto , Lactente , Feminino , Anticorpos Antibacterianos/sangue , Adulto Jovem , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Bordetella pertussis/imunologia , Idoso , Toxina Pertussis/imunologia , Recém-Nascido , Ensaio de Imunoadsorção Enzimática
11.
Immun Inflamm Dis ; 12(7): e1338, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38990142

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) infection is an important risk factor for Coronavirus Disease 2019 (COVID-19), but data on the prevalence of COVID-19 among people living with HIV (PLWH) is limited in low-income countries. Our aim was to assess the seroprevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies and associated factors among PLWH in Sierra Leone. METHODS: We conducted a cross-sectional survey of PLWH aged 18 years or older in Sierra Leone between August 2022 and January 2023. Participants were tested for SARS-CoV-2 antibodies using a rapid SARS-CoV-2 antibody (immunoglobulin M/immunoglobulin G [IgG]) kits. Stepwise logistic regression was used to explore factors associated with SARS-CoV-2 antibody seroprevalence with a significance level of p < .05. RESULTS: In our study, 33.4% (1031/3085) participants had received a COVID-19 vaccine, and 75.7% were SARS-CoV-2 IgG positive. Higher IgG seroprevalence was observed in females (77.2% vs. 71.4%, p = .001), adults over 60 years (88.2%), those with suppressed HIV RNA (80.7% vs. 51.7%, p < .001), antiretroviral therapy (ART)-experienced individuals (77.9% vs. 44.6%, p < .001), and vaccinated participants (80.7% vs. 73.2%, p < .001). Patients 60 years or older had the highest odds of IgG seroprevalence (adjusted odds ratio [aOR] = 2.73, 95% CI = 1.68-4.65). Female sex (aOR = 1.28, 95%CI = 1.05-1.56), COVID-19 vaccination (aOR = 1.54, 95% CI = 1.27-1.86), and ART (aOR = 2.20, 95% CI = 1.56-3.11) increased the odds, whereas HIV RNA ≥ 1000 copies/mL (aOR = 0.32, 95% CI = 0.26-0.40) reduced the odds of IgG seroprevalence. CONCLUSIONS: We observed a high seroprevalence of SARS-CoV-2 antibody among PLWH in Sierra Leone. We recommend the introduction of targeted vaccination for PLWH with a high risk of severe COVID-19, especially those with an unsuppressed HIV viral load.


Assuntos
Anticorpos Antivirais , COVID-19 , Infecções por HIV , Imunoglobulina G , SARS-CoV-2 , Humanos , Masculino , Feminino , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/sangue , Serra Leoa/epidemiologia , Estudos Soroepidemiológicos , Adulto , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Estudos Transversais , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Adulto Jovem , Fatores de Risco , Adolescente , Idoso , Vacinas contra COVID-19/imunologia
12.
Microb Biotechnol ; 17(7): e14518, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953907

RESUMO

Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and mortality among newborn piglets. However, current PEDV vaccines are not effective to protect the pigs from field epidemic strains because of poor mucosal immune response and strain variation. Therefore, it is indispensable to develop a novel oral vaccine based on epidemic strains. Bacillus subtilis spores are attractive delivery vehicles for oral vaccination on account of the safety, high stability, and low cost. In this study, a chimeric gene CotC-Linker-COE (CLE), comprising of the B. subtilis spore coat gene cotC fused to the core neutralizing epitope CO-26 K equivalent (COE) of the epidemic strain PEDV-AJ1102 spike protein gene, was constructed. Then recombinant B. subtilis displaying the CLE on the spore surface was developed by homologous recombination. Mice were immunized by oral route with B. subtilis 168-CLE, B. subtilis 168, or phosphate-buffered saline (PBS) as control. Results showed that the IgG antibodies and cytokine (IL-4, IFN-γ) levels in the B. subtilis 168-CLE group were significantly higher than the control groups. This study demonstrates that B. subtilis 168-CLE can generate specific systemic immune and mucosal immune responses and is a potential vaccine candidate against PEDV infection.


Assuntos
Anticorpos Antivirais , Bacillus subtilis , Vírus da Diarreia Epidêmica Suína , Esporos Bacterianos , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/imunologia , Animais , Bacillus subtilis/genética , Bacillus subtilis/imunologia , Esporos Bacterianos/genética , Esporos Bacterianos/imunologia , Camundongos , Anticorpos Antivirais/sangue , Suínos , Vacinas Virais/imunologia , Vacinas Virais/genética , Vacinas Virais/administração & dosagem , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/prevenção & controle , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Administração Oral , Citocinas/metabolismo , Imunoglobulina G/sangue , Camundongos Endogâmicos BALB C , Feminino , Técnicas de Visualização da Superfície Celular , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
13.
Parasite ; 31: 38, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38995111

RESUMO

In total, 901 dairy cow sera and data were collected from 51 farms in Nakhon Pathom, Ratchaburi and Kanchanaburi provinces (Western Region of Thailand). Serum samples were processed via the multispecies ELISA method to detect IgG antibodies against Toxoplasma gondii infection. The results demonstrated that the calculated true prevalence was 1.48% (95% CI, 0.64-2.75%) for the individual-level and 29.41% (95% CI, 18.71-43%) for the farm-level. The univariate risk factor analysis showed that the number of total owned cats, the presence of stray cats, and the frequency of cleaning per day were significant factors (p < 0.2). These three factors were subjected to logistic regression analysis, and the results revealed that the frequency of cleaning farms per day was a potential risk factor for T. gondii-seropositive farms (OR = 2.745, 95% CI, 1.15-8.69, p = 0.02). The frequency of cleaning might increase the T. gondii oocyst distribution within the barn area, thus increasing the possibility of infection. Our findings show that T. gondii continues to circulate in the dairy cow population in the western part of Thailand. The presence of cats on farms was not found to be associated with T. gondii infection, but the high frequency of cleaning the floor was, and contributed to the potential risk of infection.


Title: Prévalence et facteurs de risque de l'infection à Toxoplasma gondii chez les bovins laitiers de la région occidentale de la Thaïlande. Abstract: Au total, 901 sérums de vaches laitières et des données ont été collectés dans 51 fermes des provinces de Nakhon Pathom, Ratchaburi et Kanchanaburi (région occidentale de la Thaïlande). Les échantillons de sérum ont été traités via la méthode ELISA multi-espèces pour détecter les anticorps IgG contre l'infection à Toxoplasma gondii. Les résultats ont démontré que la prévalence réelle calculée était de 1,48 % (IC à 95 %, 0,64­2,75 %) au niveau individuel et de 29,41 % (IC à 95 %, 18,71­43 %) au niveau des exploitations. L'analyse factorielle a montré que le nombre total de chats possédés, la présence de chats errants et la fréquence quotidienne de nettoyage étaient des facteurs significatifs (p < 0,2). Ces trois facteurs ont été soumis à une analyse de régression logistique et les résultats ont révélé que la fréquence quotidienne de nettoyage des exploitations était un facteur de risque potentiel pour les exploitations séropositives à T. gondii (OR = 2,745, IC à 95 % = 1,15­8,69, p = 0,02). La fréquence du nettoyage pourrait favoriser la répartition des oocystes de T. gondii dans les étables, augmentant ainsi le risque d'infection. Nos résultats indiquent que T. gondii continue de circuler dans la population de vaches laitières de l'ouest de la Thaïlande. La présence de chats dans les fermes n'a pas été associée à l'infection à T. gondii, mais la fréquence élevée du nettoyage du sol l'était et contribuait au risque potentiel d'infection.


Assuntos
Anticorpos Antiprotozoários , Doenças dos Bovinos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Toxoplasma , Toxoplasmose Animal , Animais , Bovinos , Tailândia/epidemiologia , Toxoplasmose Animal/epidemiologia , Fatores de Risco , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Toxoplasma/imunologia , Anticorpos Antiprotozoários/sangue , Feminino , Gatos , Estudos Soroepidemiológicos , Imunoglobulina G/sangue , Ensaio de Imunoadsorção Enzimática/veterinária , Indústria de Laticínios , Prevalência , Doenças do Gato/epidemiologia , Doenças do Gato/parasitologia , Modelos Logísticos
14.
Front Immunol ; 15: 1414830, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007131

RESUMO

Introduction: Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx. Methods: We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses. Results: In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01). Conclusion: Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Imunidade Celular , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Anticorpos Antivirais/sangue , Idoso , Noruega/epidemiologia , Fatores de Risco , Imunoglobulina G/sangue
15.
Medicine (Baltimore) ; 103(28): e38983, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996095

RESUMO

RATIONALE: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease of the central nervous system that affects the meninges, brain, spinal cord, and optic nerves. GFAP astrocytopathy can coexist with a variety of antibodies, which is known as overlap syndrome. Anti-NMDAR-positive encephalitis overlap syndrome has been reported; however, encephalitis overlap syndrome with both anti-NMDAR and sulfatide-IgG positivity has not been reported. PATIENT CONCERNS: The patient was a 50-year-old male who was drowsy and had chills and weak limbs for 6 months. His symptoms worsened after admission to our hospital with persistent high fever, dysphoria, gibberish, and disturbance of consciousness. Positive cerebrospinal fluid NMDA, GFAP antibodies, and serum sulfatide antibody IgG were positive. DIAGNOSES: Autoimmune GFAP astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome. INTERVENTIONS: In addition to ventilator support and symptomatic supportive treatment, step-down therapy with methylprednisolone (1000 mg/d, halved every 3 days) and pulse therapy with human immunoglobulin (0.4 g/(kg d) for 5 days) were used. OUTCOMES: After 6 days of treatment, the patient condition did not improve, and the family signed up to give up the treatment and left the hospital. CONCLUSIONS: Patients with autoimmune GFAP astrocytopathy may be positive for anti-NMDAR and sulfatide-IgG, and immunotherapy may be effective in patients with severe conditions. LESSONS: Autoimmune GFAP astrocytopathy with nonspecific symptoms is rarely reported and is easy to be missed and misdiagnosed. GFAP astrocytopathy should be considered in patients with fever, headache, disturbance of consciousness, convulsions, and central infections that do not respond to antibacterial and viral agents. Autoimmune encephalopathy-related antibody testing should be performed as soon as possible, early diagnosis should be confirmed, and immunomodulatory therapy should be administered promptly.


Assuntos
Proteína Glial Fibrilar Ácida , Sulfoglicoesfingolipídeos , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Glial Fibrilar Ácida/imunologia , Proteína Glial Fibrilar Ácida/sangue , Sulfoglicoesfingolipídeos/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Autoanticorpos/sangue , Metilprednisolona/uso terapêutico , Encefalite/diagnóstico , Encefalite/imunologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Astrócitos/imunologia , Astrócitos/patologia , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/imunologia
16.
Arch Virol ; 169(8): 163, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990396

RESUMO

Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness.


Assuntos
Anticorpos Antivirais , Imunidade Humoral , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae , Receptor 4 Toll-Like , Vacinas de Produtos Inativados , Animais , Subtipo H7N9 do Vírus da Influenza A/imunologia , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/imunologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Camundongos , Anticorpos Antivirais/imunologia , Cães , Células Madin Darby de Rim Canino , Vacinas de Produtos Inativados/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Feminino , Anticorpos Neutralizantes/imunologia , Proteção Cruzada/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Adjuvantes de Vacinas , Imunoglobulina G/imunologia , Imunoglobulina G/sangue
17.
Nat Commun ; 15(1): 5878, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38997292

RESUMO

The bat immune system features multiple unique properties such as dampened inflammatory responses and increased tissue protection, explaining their long lifespan and tolerance to viral infections. Here, we demonstrated that body temperature fluctuations corresponding to different physiological states in bats exert a large impact on their antibody repertoires. At elevated temperatures typical for flight, IgG from the bat species Myotis myotis and Nyctalus noctula show elevated antigen binding strength and diversity, recognizing both pathogen-derived antigens and autoantigens. The opposite is observed at temperatures reflecting inactive physiological states. IgG antibodies of human and other mammals, or antibodies of birds do not appear to behave in a similar way. Importantly, diversification of bat antibody specificities results in preferential recognition of damaged endothelial and epithelial cells, indicating an anti-inflammatory function. The temperature-sensitivity of bat antibodies is mediated by the variable regions of immunoglobulin molecules. Additionally, we uncover specific molecular features of bat IgG, such as low thermodynamic stability and implication of hydrophobic interactions in antigen binding as well as high prevalence of polyreactivity. Overall, our results extend the understanding of bat tolerance to disease and inflammation and highlight the link between metabolism and immunity.


Assuntos
Quirópteros , Imunoglobulina G , Quirópteros/imunologia , Animais , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Humanos , Temperatura , Especificidade de Anticorpos/imunologia , Antígenos/imunologia , Autoantígenos/imunologia , Autoantígenos/metabolismo
18.
BMC Infect Dis ; 24(1): 696, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997625

RESUMO

BACKGROUND AND PURPOSE: The seroprevalence of antibodies against measles, mumps, and rubella (MMR) was evaluated 17 years following a mass vaccination campaign in individuals aged 2 to 22 years who had received routine immunization but were not eligible for an extended immunization program. METHODS: Samples were acquired from Iran's National Measles Laboratory (NML), with individuals showing positive IgM results excluded. Out of the samples collected in 2020, a random selection of 290 serum samples was chosen, representing individuals between the ages of 2 and 22 years from diverse regions in the country. These samples were subjected to analysis using an enzyme-linked immunosorbent assay (ELISA) to quantify specific IgG antibodies against MMR. RESULTS: The seroprevalence rates of antibodies for measles, mumps, and rubella were determined to be 76.2%, 89.3%, and 76.9%, respectively. Younger age groups exhibited higher seropositivity rates for measles and mumps, whereas the 7- to 11-year-old group demonstrated the highest seropositivity rate for rubella. A reduction in antibody status was observed from younger to older age groups, particularly those aged 17-22. CONCLUSION: The study unveiled suboptimal antibody levels for measles and rubella, highlighting the necessity for further investigation and potential adjustments to future vaccination strategies. Moreover, the decline in antibody status post-vaccination can accumulate in seronegative individuals over time, elevating the risk of outbreaks.


Assuntos
Anticorpos Antivirais , Vacinação em Massa , Vacina contra Sarampo-Caxumba-Rubéola , Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Humanos , Criança , Adolescente , Irã (Geográfico)/epidemiologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Pré-Escolar , Anticorpos Antivirais/sangue , Sarampo/epidemiologia , Sarampo/imunologia , Sarampo/prevenção & controle , Masculino , Feminino , Adulto Jovem , Estudos Soroepidemiológicos , Rubéola (Sarampo Alemão)/imunologia , Rubéola (Sarampo Alemão)/epidemiologia , Rubéola (Sarampo Alemão)/prevenção & controle , Caxumba/imunologia , Caxumba/epidemiologia , Caxumba/prevenção & controle , Vacinação em Massa/estatística & dados numéricos , Imunoglobulina G/sangue , Vacinação/estatística & dados numéricos , Ensaio de Imunoadsorção Enzimática
19.
Orphanet J Rare Dis ; 19(1): 266, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010060

RESUMO

BACKGROUND: The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. METHODS: We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. RESULTS: IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. CONCLUSIONS: Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Pericardite , Humanos , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Pericardite/tratamento farmacológico , Pericardite/patologia , Pericardite/diagnóstico por imagem , Feminino , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/patologia , Idoso , Adulto , Arterite/tratamento farmacológico , Arterite/diagnóstico por imagem , Arterite/patologia , Imunoglobulina G , Estudos de Coortes , Glucocorticoides/uso terapêutico
20.
BMC Pediatr ; 24(1): 425, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956534

RESUMO

BACKGROUND: Seroprevalence studies provide information on the true extent of infection and capture demographic and geographic differences, indicating the level of immunity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We sought to provide local evidence of SARS-CoV-2 exposure in school-aged children during in-class teaching in Maputo City and Province, Mozambique. METHODS: Between August and November 2022, we performed a cross-sectional study in school-aged children in four schools in rural, peri-urban, and urban areas of Maputo City and Province. A point-of-care test was used to evaluate SARS-CoV-2 antigens and anti-SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. Descriptive statistics were used to estimate the prevalence of the antigens and antibodies. Multiple logistic regression models were used to estimate the adjusted odds ratio (AOR) for the factors associated with anti-SARS-CoV-2 antibodies. RESULTS: A total of 736 school-aged children were analyzed. The prevalence of the SARS-CoV-2 antigen was 0.5% (4/736). The prevalence of SARS-CoV-2 antigens was 0.0% (0/245), 0.8% (2/240) and 0.8% (2/251), in the rural, peri-urban and urban areas respectively. The overall seroprevalence of the anti-SARS-CoV-2 antibodies (IgG or IgM) was 80.7% (594/736). In rural area anti-SARS-CoV-2 IgG or IgM antibodies were detected in 76.7% (188/245), while in peri-urban area they were detected in 80.0% (192/240) and in urban area they were detected in 85.3% (214/251). In the adjusted logistic regression model, school-aged children from the urban area were more likely to have anti-SARS-CoV-2 IgG or IgM antibodies than were school-aged children from the rural area (adjusted odds ratio: 1.679; 95% CI: 1.060-2.684; p-value = 0.028). CONCLUSIONS: During the in-class teaching period, active SARS-CoV-2 cases in school-aged children were observed. More than half of the school-aged children were exposed to SARS-CoV-2, and SARS-CoV-2 was significantly more common in the schools at the urban area than in the school in the rural area at Maputo City and Province.


Assuntos
Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/imunologia , Estudos Transversais , Criança , Masculino , Feminino , Moçambique/epidemiologia , SARS-CoV-2/imunologia , Estudos Soroepidemiológicos , Anticorpos Antivirais/sangue , Imunoglobulina M/sangue , Imunoglobulina G/sangue , Prevalência , Instituições Acadêmicas
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