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1.
Front Immunol ; 13: 853682, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493446

RESUMO

The antibody and T cell responses after SARS-CoV-2 vaccination have not been formally compared between kidney and liver transplant recipients. Using a multiplex assay, we measured IgG levels against 4 epitopes of SARS-CoV-2 spike protein and nucleocapsid (NC) antigen, SARS-CoV-2 variants, and common coronaviruses in serial blood samples from 52 kidney and 50 liver transplant recipients undergoing mRNA SARS-CoV-2 vaccination. We quantified IFN-γ/IL-2 T cells reactive against SARS-CoV-2 spike protein by FluoroSpot. We used multivariable generalized linear models to adjust for the differences in immunosuppression between groups. In liver transplant recipients, IgG levels against every SARS-CoV-2 spike epitope increased significantly more than in kidney transplant recipients (MFI: 19,617 vs 6,056; P<0.001), a difference that remained significant after adjustments. Vaccine did not affect IgG levels against NC nor common coronaviruses. Elicited antibodies recognized all variants tested but at significantly lower strength than the original Wuhan strain. Anti-spike IFN-γ-producing T cells increased significantly more in liver than in kidney transplant recipients (IFN-γ-producing T cells 28 vs 11 spots/5x105 cells), but this difference lost statistical significance after adjustments. SARS-CoV-2 vaccine elicits a stronger antibody response in liver than in kidney transplant recipients, a phenomenon that is not entirely explained by the different immunosuppression.


Assuntos
COVID-19 , Transplante de Fígado , Vacinas Virais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Epitopos , Humanos , Imunoglobulina G , Rim , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
2.
Respir Res ; 23(1): 141, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35641962

RESUMO

BACKGROUND: Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD. METHODS: We measured serum IgG subclass concentrations of 489 hospitalized patients with COPD who were enrolled in the Rapid Transition Program (clinicaltrials.gov identifier NCT02050022). To evaluate the impact of IgG subclass deficiency on 1-year mortality, Cox proportional hazards regression analyses were performed with adjustments for potential confounders. RESULTS: Deficiencies in IgG1, IgG2, IgG3, and IgG4 were present in 1.8%, 12.1%, 4.3%, and 11.2% of patients, respectively. One-year mortality was 56% in patients with IgG1 deficiency, 27% in IgG2 deficiency, 24% in IgG3 deficiency, and 31% in IgG4 deficiency. Cox proportional modeling showed that IgG1 and IgG4 deficiencies increased the 1-year mortality risk with an adjusted hazard ratio of 3.92 (95% confidence interval [CI] = 1.55-9.87) and 1.74 (95% CI = 1.02-2.98), respectively. Neither IgG2 nor IgG3 deficiency significantly increased 1-year mortality. Two or more IgG subclass deficiencies were observed in 5.3%. Patients with 2 or more IgG subclass deficiencies had a higher 1-year mortality than those without any deficiencies (46.2% vs. 19.7%, p < 0.001), with an adjusted hazard ratio of 2.22 (95% CI = 1.18-4.17). CONCLUSIONS: IgG1 and IgG4 deficiency was observed in 1.8% and 11.2% of hospitalized patients with COPD, respectively, and these deficiencies were associated with a significantly increased risk of 1-year mortality.


Assuntos
Deficiência de IgG , Síndromes de Imunodeficiência , Doença Pulmonar Obstrutiva Crônica , Humanos , Deficiência de IgG/diagnóstico , Imunoglobulina G , Doença Pulmonar Obstrutiva Crônica/diagnóstico
3.
Front Immunol ; 13: 865486, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686131

RESUMO

De novo immune responses to myeloid and other blood-borne tumors are notably limited and ineffective, making our ability to promote immune responses with vaccines a major challenge. While focus has been largely on cytotoxic cell-mediated tumor eradication, B-cells and the antibodies they produce also have roles in anti-tumor responses. Indeed, therapeutic antibody-mediated tumor cell killing is routinely employed in patients with hematolymphoid cancers, but whether endogenous antibody responses can be incited to blood-born tumors remains poorly studied. A major limitation of immunoglobulin therapies is that cell surface expression of tumor-associated antigen (TAA) targets is dynamic and varied, making promotion of polyclonal, endogenous B cell responses appealing. Since many TAAs are self-antigens, developing tumor vaccines that enable production of antibodies to non-polymorphic antigen targets remains a challenge. As B cell responses to RNA vaccines are known to occur, we employed the Viral Replicon Particles (VRP) which was constructed to encode mouse FLT3. The VRP-FLT3 vaccine provoked a rapid IgG B-cell response to this self-antigen in leukemia and lymphoma mouse models. In addition, IgGs to other TAAs were also produced. Our data suggest that vaccination with RNA viral particle vectors incites a loss of B-cell tolerance that enables production of anti-tumor antibodies. This proof of principle work provides impetus to employ such strategies that lead to a break in B-cell tolerance and enable production of broadly reactive anti-TAA antibodies as potential future therapeutic agents for patients with hematolymphoid cancers.


Assuntos
Alphavirus , Vacinas Anticâncer , Neoplasias , Vacinas Virais , Animais , Antígenos de Neoplasias , Humanos , Imunoglobulina G , Camundongos , Neoplasias/genética , Replicon
4.
Biomed Res Int ; 2022: 4792374, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686237

RESUMO

Background: Liver cancer (LC) is the most devastating disease affecting a large set of populations in the world. The mortality due to LC is escalating, indicating the lack of effective therapeutic options. Immunotherapeutic agents may play an important role against cancer cells. As immune cells, especially T lymphocytes, which are part of cancer immunology, the design of vaccine candidates for cytotoxic T lymphocytes may be an effective strategy for curing liver cancer. Results: In our study, based on an immunoinformatics approach, we predicted potential T cell epitopes of MHC class I molecules using integrated steps of data retrieval, screening of antigenic proteins, functional analysis, peptide synthesis, and experimental in vivo investigations. We predicted the binding affinity of epitopes LLECADDRADLAKY, VSEHRIQDKDGLFY, and EYILSLEELVNGMY of LC membrane-bounded extracellular proteins including butyrophilin-like protein-2 (BTNL2), glypican-3 (GPC3), and serum albumin (ALB), respectively, with MHC class I molecules (allele: HLA-A∗01:01). These T cell epitopes rely on the level of their binding energy and antigenic properties. We designed and constructed a trivalent immunogenic model by conjugating these epitopes with linkers to activate cytotoxic T cells. For validation, the nonspecific hematological assays showed a significant rise in the count of white blood cells (5 × 109/l), lymphocytes (13 × 109/l), and granulocytes (5 × 109/l) compared to the control after administration of trivalent peptides. Specific immunoassays including granzyme B and IgG ELISA exhibited the significant concentration of these effector molecules in blood serum, indicating the activity of cytotoxic T cells. Granzyme concentration increased to 1050 pg/ml at the second booster dose compared to the control (95 pg/ml), while the concentration of IgG raised to 6 g/l compared to the control (2 g/l). Conclusion: We concluded that a potential therapeutic trivalent vaccine can activate and modulate the immune system to cure liver cancer on the basis of significant outcomes of specific and nonspecific assays.


Assuntos
Vacinas Anticâncer , Neoplasias Hepáticas , Animais , Epitopos de Linfócito T , Antígenos de Histocompatibilidade Classe I , Imunoglobulina G , Neoplasias Hepáticas/terapia , Peptídeos , Ratos , Ratos Sprague-Dawley , Linfócitos T Citotóxicos
5.
PLoS One ; 17(6): e0268780, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35679232

RESUMO

OBJECTIVES: Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease. METHODS: This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls. RESULTS: After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0-125.0), baseline IgG 3-5 g/l: 99.9 AU/ml (95%CI 14.4-400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0-400.0), healthy controls 250.0 AU/ml (95%CI 209.0-358.0), p = 0.007. CONCLUSION: In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.


Assuntos
COVID-19 , Vacinas , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Humanos , Imunidade Humoral , Imunoglobulina G , SARS-CoV-2 , Vacinação , Vacinas Sintéticas
6.
PLoS One ; 17(6): e0266214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35679264

RESUMO

We determined the association between Toxoplasma gondii (T. gondii) infection and insomnia. Through an age-and gender-matched case-control study, 577 people with insomnia (cases) and 577 people without insomnia (controls) were tested for anti-T. gondii IgG and IgM antibodies using commercially available enzyme-immunoassays. Anti-T. gondii IgG antibodies were found in 71 (12.3%) of 577 individuals with insomnia and in 46 (8.0%) of 577 controls (OR = 1.62; 95% CI: 1.09-2.39; P = 0.01). Men with insomnia had a higher (16/73: 21.9%) seroprevalence of T. gondii infection than men without insomnia (5/73: 6.8%) (OR: 3.81; 95% CI: 1.31-11.06; P = 0.009). The rate of high (>150 IU/ml) anti-T. gondii IgG antibody levels in cases was higher than the one in controls (OR = 2.21; 95% CI: 1.13-4.31; P = 0.01). Men with insomnia had a higher (8/73: 11.0%) rate of high anti-T. gondii IgG antibody levels than men without insomnia (0/73: 0.0%) (P = 0.006). The rate of high anti-T. gondii IgG antibody levels in cases >50 years old (11/180: 6.1%) was higher than that (3/180: 1.7%) in controls of the same age group (OR: 3.84; 95% CI: 1.05-14.00; P = 0.05). No difference in the rate of IgM seropositivity between cases and controls was found (OR = 1.33; 95% CI: 0.57-3.11; P = 0.50). Results of this seroepidemiology study suggest that infection with T. gondii is associated with insomnia. Men older than 50 years with T. gondii exposure might be prone to insomnia. Further research to confirm the association between seropositivity and serointensity to T. gondii and insomnia is needed.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Toxoplasma , Toxoplasmose , Anticorpos Antiprotozoários , Estudos de Casos e Controles , Humanos , Imunoglobulina G , Imunoglobulina M , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Toxoplasmose/complicações , Toxoplasmose/epidemiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-35680348

RESUMO

INTRODUCTION: Hospital-wide SARS-CoV-2 seroprevalence is rarely explored and can identify areas of unexpected risk. We determined the seroprevalence against SARS-CoV-2 in all health care workers (HCW) at a hospital. METHODS: Cross-sectional study (14-27/04/2020). We determined SARS-CoV-2 IgG by ELISA in all HCW including external workers of a teaching hospital in Madrid. They were classified by professional category, working area, and risk for SARS-CoV-2 exposure. RESULTS: Among 2919 HCW, 2590 (88,7%) were evaluated. The mean age was 43.8 years (SD 11.1), and 73.9% were females. Globally, 818 (31.6%) workers were IgG positive with no differences for age, sex or previous diseases. Of these, 48.5% did not report previous symptoms. Seropositivity was more frequent in high- (33.1%) and medium- (33.8%) than in low-risk areas (25.8%, p=0.007), but not for hospitalization areas attending COVID-19 and non-COVID-19 patients (35.5 vs 38.3% p>0.05). HWC with a previous SARS-CoV2 PCR-positive test were IgG seropositive in 90.8%. By multivariate logistic regression analysis seropositivity was significantly associated with being physicians (OR 2.37, CI95% 1.61-3.49), nurses (OR 1.67, CI95% 1.14-2.46), nurse assistants (OR 1.84, CI95% 1.24-2.73), HCW working at COVID-19 hospitalization areas (OR 1.71, CI95% 1.22-2.40), non-COVID-19 hospitalization areas (OR 1.88, CI95% 1.30-2.73), and at the Emergency Room (OR 1.51, CI95% 1.01-2.27). CONCLUSIONS: Seroprevalence uncovered a high rate of infection previously unnoticed among HCW. Patients not suspected of having COVID-19 as well as asymptomatic HCW may be a relevant source for nosocomial SARS-CoV-2 transmission.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , COVID-19/epidemiologia , Estudos Transversais , Feminino , Pessoal de Saúde , Hospitais de Ensino , Humanos , Imunoglobulina G , Masculino , RNA Viral , Estudos Soroepidemiológicos
8.
Cells ; 11(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35681515

RESUMO

The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents.


Assuntos
Eosinófilos , Interleucina-5 , Autofagia , DNA , Imunoglobulina G
9.
Int J Mol Sci ; 23(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35682724

RESUMO

The involvement of immunoglobulin (Ig) G3 in the humoral immune response to SARS-CoV-2 infection has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) in COVID-19. The exact molecular mechanism is unknown, but it is thought to involve this IgG subtype's differential ability to fix, complement and stimulate cytokine release. We examined the binding of convalescent patient antibodies to immobilized nucleocapsids and spike proteins by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. IgG3 was a major immunoglobulin found in all samples. Differential analysis of the spectral signatures found for the nucleocapsid versus the spike protein demonstrated that the predominant humoral immune response to the nucleocapsid was IgG3, whilst for the spike protein it was IgG1. However, the spike protein displayed a strong affinity for IgG3 itself, as it would bind from control plasma samples, as well as from those previously infected with SARS-CoV-2, similar to the way protein G binds IgG1. Furthermore, detailed spectral analysis indicated that a mass shift consistent with hyper-glycosylation or glycation was a characteristic of the IgG3 captured by the spike protein.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Anticorpos Antivirais , Humanos , Imunoglobulina G , Nucleocapsídeo , SARS-CoV-2
10.
J Clin Virol ; 152: 105193, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35660747

RESUMO

BACKGROUND: The mRNA Covid-19 vaccine (BNT162b2) is administered in two doses with 21 days interval. On 4th October 2021 European Medicines Agency approved administration of a booster dose in at least 6 months after the second dose for people aged 18 years and older. OBJECTIVES: In the present study we compare the anti-SARS-COV-2 IgG and IgA antibody responses post complete vaccination, 7 months later and after the 3rd (booster) dose of the BNT162B2 vaccine in healthy adults. STUDY DESIGN: The levels of vaccine IgG and IgA antibodies to SARS-CoV-2 were assessed in serum samples obtained from individuals vaccinated with two doses and a booster of BNT162b2 vaccine. Samples were tested using the SARS-CoV-2 receptor-binding domain (RCB) IgG and IgA semi-quantitative commercial ELISA assay. RESULTS: The geometric mean of the anti-SARS-COV-2 IgG and IgA antibody level 7 months after vaccination of 90 healthy adults with BNT162B2 vaccine decreased significantly from 12.0 to 5.4 and 5.6 to 2.3, respectively. After the third dose of the same vaccine, the antibody level increased again, to values higher than at the beginning after the second dose. CONCLUSIONS: Significant decrease of antibody levels within a few months after full vaccination could result in the higher risk of SARS-CoV-2 infection, especially when new variants of the virus emerge. The booster could be crucial for protection against new SARS-CoV-2 variants. The antibody level seems to decrease slower in vaccinated individuals with history of COVID-19 and in younger individuals.


Assuntos
COVID-19 , Imunoglobulina A , Adulto , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunoglobulina G , SARS-CoV-2 , Vacinação , Vacinas de Produtos Inativados
11.
Vet Immunol Immunopathol ; 249: 110442, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35662038

RESUMO

The aim of this study was to determine the diagnostic accuracy of digital serum total protein (TP) and digital Brix refractometers in estimating different passive immunity levels (<10, <18, <25 mg/mL) in dairy calves. Blood samples were collected from 260 apparently healthy Holstein calves, aged 2-7 days. Serum IgG concentrations were measured using digital Brix and TP refractometers and the radial immunodiffusion (RID) assay, as the gold standard. Data were analyzed by a receiver operating characteristics (ROC) analysis, the area under the ROC curves (AUC) and Cohen's kappa (κ). Optimal thresholds were determined as < 8.4, < 9.0 and < 9.4% for the digital Brix refractometer, and < 5.0, < 5.4 and < 5.8 g/dL for the serum TP refractometer in estimating IgG concentrations of < 10, < 18, < 25 mg/mL, respectively. The sensitivity (Se) and specificity (Sp) of the Brix refractometer were 96.3% and 88.8% for < 8.4% Brix, 97.0% and 83.4% for < 9.0% Brix, and 85.5% and 77.8% for < 9.4% Brix, respectively. The Se and Sp of the serum TP refractometer were 96.3% and 90.1% for < 5.0 g/dL, 91.0% and 89.6% for < 5.4 g/dL, 79.6% and 85.2% for < 5.8 g/dL, respectively. The discriminant ability of the refractometers was moderately accurate in estimating IgG concentrations of < 10 and < 18 mg/mL, and highly accurate in estimating IgG concentrations of < 25 mg/mL. Both refractometers substantially agreed with RID-IgG results and almost perfectly agreed with each other. In conclusion, the digital Brix and digital serum TP refractometers offer a good utility for determining different passive immunity levels in dairy calves.


Assuntos
Imunoglobulina G , Refratometria , Animais , Animais Recém-Nascidos , Bovinos , Colostro , Feminino , Imunidade Materno-Adquirida , Imunodifusão/métodos , Imunodifusão/veterinária , Gravidez , Refratometria/métodos , Refratometria/veterinária , Sensibilidade e Especificidade
12.
PLoS One ; 17(6): e0264298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35679259

RESUMO

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR] = 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR = 4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR = 0.25; CI 0.08, 0.80 and aOR = 0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR = 0.16; CI 0.03, 0.97 and aOR = 0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.


Assuntos
COVID-19 , Faringite , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/terapia , Tosse , Humanos , Imunização Passiva , Imunoglobulina G , RNA Viral , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
13.
PLoS One ; 17(6): e0269917, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35687563

RESUMO

The purpose of this study was to identify factors associated with the increase in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S1) protein and neutralizing antibody titer following SARS-CoV-2 vaccination. This observational study was conducted among healthcare workers working for a private hospital group in Fukushima Prefecture, Japan. Two blood samples were obtained from each participant. The first sample was obtained before the first dose of BNT162b2 (Pfizer-BioNTech) vaccine, and a second sample was obtained approximately 6 weeks later. Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein, immunoglobulin M (IgM) antibody against SARS-CoV-2 N-protein, and neutralizing activity were measured using the chemiluminescent immunoassay with iFlash 3000. A total of 231 healthcare workers who agreed to participate, and were negative for anti-SARS-CoV-2 IgM antibodies at enrollment, were included in the analysis. All participants had elevated IgG antibodies and neutralizing activity above the cutoff values. A total of 174 (75.3%) and 208 (90.0%) participants experienced adverse reactions after the first and second vaccine doses, respectively. Younger age, female sex, not taking immunosuppressive or antipyretic analgesic medication regularly, a lack of local adverse reactions after the first dose, and the presence of adverse reactions (fever, muscle, and joint pain) after the second dose were associated with higher IgG antibody titers and neutralizing activity. Intake of analgesic antipyretic for adverse reactions to vaccines was not significantly associated with antibody and neutralizing activity titer production. Immune responses after vaccination may differ among individuals, and continued countermeasures to prevent SARS-CoV-2 infection are vital.


Assuntos
Antipiréticos , COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Pessoal de Saúde , Humanos , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação
14.
Sci Immunol ; 7(72): eabh3816, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35687695

RESUMO

The gut microbiome elicits antigen-specific immunoglobulin G (IgG) at steady state that cross-reacts to pathogens to confer protection against systemic infection. The role of gut microbiome-specific IgG antibodies in the development of the gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we show that gut microbiome-induced maternal IgG is transferred to the neonatal intestine through maternal milk via the neonatal Fc receptor and directly inhibits Citrobacter rodentium colonization and attachment to the mucosa. Enhanced neonatal immunity against oral C. rodentium infection was observed after maternal immunization with a gut microbiome-derived IgG antigen, outer membrane protein A, or induction of IgG-inducing gut bacteria. Furthermore, by generating a gene-targeted mouse model with complete IgG deficiency, we demonstrate that IgG knockout neonates are more susceptible to C. rodentium infection and exhibit alterations of the gut microbiome that promote differentiation of interleukin-17A-producing γδ T cells in the intestine, which persist into adulthood and contribute to increased disease severity in a dextran sulfate sodium-induced mouse model of colitis. Together, our studies have defined a critical role for maternal gut microbiome-specific IgG antibodies in promoting immunity against enteric pathogens and shaping the development of the gut microbiome and immune cells in early life.


Assuntos
Colite , Infecções por Enterobacteriaceae , Microbioma Gastrointestinal , Animais , Citrobacter rodentium , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/prevenção & controle , Imunoglobulina G , Camundongos
15.
BMC Microbiol ; 22(1): 156, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690730

RESUMO

OBJECTIVE & AIM: The coronavirus disease, so far (COVID-19) has brought about millions of infections and fatalities throughout the world. Our aim was to determine the correlation between rubella IGG titers with the severity COVID-19.  MATERIALS & METHODS: This study was conducted among COVID-19 confirmed patients over 18 years of age. The disease severity levels were categorized by WHO interim guidance. The rubella-specific IgG antibody-titer spectrum was measured (within first 48 h of hospitalization) by enzyme-linked immunosorbent assay (ELISA). RESULT: In a study of 46 inpatients with varying COVID-19 disease severity (mild, moderate, severe, and critical), we observed a negative correlation between rubella IgG antibody titers and COVID-19 severity (P-Value = 0.017), There was an interaction between COVID-19 vaccination history and rubella IGG on severity COVID-19 (P-Value = 0.0015). There was an interaction between age group under 44 years (including national measles- rubella (MR) vaccination in Iran) and rubella IGG titers on severity COVID-19 too (p-value = 0.014). CONCLUSION: In conclusion, MR vaccination seems to have a positive effect in reducing the severity of the disease, emphasizing that, the important and separate effect of the IGG rubella (due to natural or extrinsic immunity) titers is determining.


Assuntos
COVID-19 , Rubéola (Sarampo Alemão) , Adolescente , Adulto , Anticorpos Antivirais , Vacinas contra COVID-19 , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G
16.
J Neuroinflammation ; 19(1): 140, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690819

RESUMO

BACKGROUND: Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial. METHODS: We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing. RESULTS: These experiments showed that patient's anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient's antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice. CONCLUSIONS: Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.


Assuntos
Moléculas de Adesão Celular Neuronais , Doenças do Sistema Nervoso , Animais , Autoanticorpos , Moléculas de Adesão Celular Neuronais/metabolismo , Imunoglobulina G/farmacologia , Camundongos , Doenças do Sistema Nervoso/patologia , Neurônios
17.
Eur Rev Med Pharmacol Sci ; 26(10): 3787-3796, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35647861

RESUMO

OBJECTIVE: In a prospective study, SARS-CoV-2 IgG seroprevalence was assessed during the second pandemic wave (W2) in a cohort of Inflammatory Bowel Disease (IBD) patients using biologics. The secondary aim was to compare, in the same cohort, the frequency of seropositivity and of COVID-19 during the second vs. the first (W1) wave. PATIENTS AND METHODS: From November 2020 to March 2021, SARS-CoV-2 IgG seropositivity and the prevalence of COVID-19 were assessed in a cohort of IBD patients using biologics already studied at W1. INCLUSION CRITERIA: age ≥ 18 years; diagnosis of IBD; follow-up; written consent. EXCLUSION CRITERIA: SARS-CoV-2 vaccination. Risk factors for infection, compatible symptoms, history of infection or COVID-19, nasopharyngeal swab test were recorded. Data were expressed as median [range]. The χ2 test, Student's t-test, logistic regression analysis was used. RESULTS: IBD cohort at W1 and W2 included 85 patients: 45 CD (52.9%), 40 UC (47.1%). When comparing the same 85 patients at W2 vs. W1, a higher SARS-CoV-2 seroprevalence at W2 was at the limit of the statistical significance (9.4% vs. 2.3%; p=0.05). The prevalence of COVID-19 at W2 vs. W1 was 3.5% (3/85) vs. 0% (0/85) (p=0.08). Contacts with COVID-19 patients and symptoms compatible with COVID-19 were more frequent at W2 vs. W1 (18.8 % vs. 0%; p=0.0001; 34.1% vs. 15.3%; p=0.004). At W2, history of contacts and new onset diarrhea were more frequent in seropositive patients [4/8 (50%) vs. 12/77 (15.6%); p=0.01 and 4/8 (50%) vs. 2/77 (2.6%); p=0.0001]. At W2, the risk factors for seropositivity included cough, fever, new onset diarrhea, rhinitis, arthromyalgia, dysgeusia/anosmia at univariate (p<0.05), but not at multivariate analysis. History of contacts was the only risk factor for seropositivity at univariate (p=0.03), but not at multivariate analysis (p=0.1). CONCLUSIONS: During W2, characterized by a high viral spread, IBD and biologics appeared not to increase the prevalence of SARS-CoV-2 infection or COVID-19 disease. New onset diarrhea mimicking IBD relapse may be observed in patients with SARS-CoV-2 infection.


Assuntos
Produtos Biológicos , COVID-19 , Doenças Inflamatórias Intestinais , Adolescente , Anticorpos Antivirais , Produtos Biológicos/uso terapêutico , COVID-19/epidemiologia , Vacinas contra COVID-19 , Diarreia , Humanos , Imunoglobulina G , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Recidiva Local de Neoplasia , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Estudos Soroepidemiológicos
18.
PLoS One ; 17(6): e0269253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35648773

RESUMO

BACKGROUND: Hepatitis E virus (HEV) infection is responsible for inflammatory liver disease and can cause severe health problems. Because the seroprevalence of HEV varies within different population groups and between regions of the continent, we conducted a systematic review on the topic in order to provide evidence for targeted prevention strategies. METHODS: We performed a systematic review in PubMed, SCIELO, LILACS, EBSCO, and Cochrane Library and included reports up to 25 May 2021 (PROSPERO registration number: CRD42020173934). We assessed the risk of bias, publication bias, and heterogeneity between studies and conducted a random-effect meta-analysis for proportions using a (binomial-normal) generalized linear mixed model (GLMM) fitted by Maximum Likelihood (ML). We also reported other characteristics like genotype and risk factors. RESULTS: Of 1212 identified records, 142 fulfilled the inclusion criteria and were included in the qualitative analysis and 132 in the quantitative analysis. Our random-effects GLMM pooled overall estimate for past infection (IgG) was 7.7% (95% CI 6.4%-9.2%) with high heterogeneity (I2 = 97%). We found higher seroprevalence in certain population groups, for example in people with pig related exposure for IgG (ranges from 6.2%-28% and pooled estimate of 13.8%, 95% CI: 7.6%-23.6%), or with diagnosed or suspected acute viral hepatitis for IgM (ranges from 0.3%-23.9% and pooled estimate of 5.5%, 95% CI: 2.0%-14.1%). Increasing age, contact with pigs and meat products, and low socioeconomic conditions are the main risk factors for HEV infection. Genotype 1 and 3 were documented across the region. CONCLUSION: HEV seroprevalence estimates demonstrated high variability within the Americas. There are population groups with higher seroprevalence and reported risk factors for HEV infection that need to be prioritized for further research. Due to human transmission and zoonotic infections in the region, preventive strategies should include water sanitation, occupational health, and food safety.


Assuntos
Vírus da Hepatite E , Hepatite E , América , Humanos , Imunoglobulina G , Estudos Soroepidemiológicos
19.
BMJ Case Rep ; 15(6)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35649620

RESUMO

Immunoglobulin G4-related disease (IgG4-RD) is a rare fibroinflammatory immune-mediated condition which can affect multiple organ systems and form mass-like lesions. Initial presentation can mimic other diseases such as pancreatic malignancy when there is pancreatic involvement or tuberculosis (TB) when there are pulmonary lesions or hypertrophic pachymeningitis (HP). Here, we report a novel case of IgG4-RD presenting as bilateral subdural haematomas with additional findings. Our patient is a male who presented with headaches and blurred vision. Physical examination showed disconjugate gaze with a fixed pupil. Trauma survey radiologic imaging revealed a pancreatic mass concerning for malignancy. Subsequent workup found hypophysitis with optic chiasm compression and hypopituitarism, mediastinal lymphadenopathy and HP. Laboratory values showed an elevated serum IgG4 level and latent TB. Our case adds to the existing IgG4-RD literature by highlighting a unique presentation. It is important to maintain it on the differential diagnosis especially in multisystemic presentations with competing diagnoses.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Linfadenopatia , Meningite , Diagnóstico Diferencial , Humanos , Hipertrofia/diagnóstico , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/patologia , Linfadenopatia/diagnóstico , Masculino , Meningite/diagnóstico
20.
Sci Rep ; 12(1): 9147, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650227

RESUMO

Recently, immune response to coronavirus disease (COVID-19) has attracted attention where an association between higher antibody titer and worsening disease severity has been reported. However, our experiences with severe COVID-19 patients with low antibody titers led to hypothesizing that suppressed humoral immune response may be associated with poorer prognosis in severe COVID19. In this study, antibody titers in severe COVID19 patients were measured at 7, 10, 12, and 14 days after onset. Patients were divided into survivors and non-survivors. SARS-CoV-2 IgM in survivors and non-survivors were 0.06 AU and 0.02 AU (P = 0.048) at 10 days, 0.1 AU and 0.03 AU (P = 0.02) at 12 days, and 0.17 AU and 0.06 AU (P = 0.02) at 14 days. IgG in survivors and non-survivors were 0.01 AU and 0.01 AU (P = 0.04) at 7 days, 0.42 AU and 0.01 AU (P = 0.04) at 12 days, and 0.42 AU and 0.01 AU (P = 0.02) at 14 days. Multivariate analysis showed better survival among patients with IgM positivity at 12 days (P = 0.04), IgG positivity at 12 days (P = 0.04), IgM positivity at 14 days (P = 0.008), and IgG positivity at 14 days (P = 0.005). In severe COVID-19, low antibody titers on days 12 and 14 after onset were associated with poorer prognosis.


Assuntos
COVID-19 , Anticorpos Antivirais , Humanos , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2
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