RESUMO
Several studies have investigated the antibody response to SARS-CoV-2, focusing particularly on the systemic humoral immune response and the production of immunoglobulin G (IgG) antibodies. IgA antibodies play a crucial role in protecting against respiratory viral infections but have also been associated with the pathophysiology of COVID-19. We performed a prospective study of 169 COVID-19 patients - 50 with critical/severe (ICU), 47 with moderate (Non-ICU), and 72 with asymptomatic COVID-19 - to explore the humoral immune response to SARS-CoV-2 infection. We found that the early systemic IgA response strongly induced in patients with severe disease did not block IgG neutralization functions and activated FcRs more effectively than IgG. However, even if SIgA levels were high, mucosal IgA antibodies could not control the infection effectively in patients with severe disease. Our findings highlight the complexity of the immune response to SARS-CoV-2 exhibiting high systemic levels of IgA with strong neutralizing capacity in severe cases, together with higher levels of IgA-FcR activation than in asymptomatic patients. They also suggest the need for further research to fully understand the role of IgA and its structural alterations in mucosal tissues in cases of severe disease and the impact of these antibodies on disease progression.
Assuntos
Anticorpos Antivirais , COVID-19 , Imunidade nas Mucosas , Imunoglobulina A , Imunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Imunoglobulina A/imunologia , Estudos Prospectivos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Idoso , Adulto , Anticorpos Neutralizantes/imunologia , Índice de Gravidade de Doença , Imunidade HumoralRESUMO
Understanding the immune response generated by SARS-CoV-2 is critical for assessing efficient therapeutic protocols and gaining insights into the durability of protective immunity. The current work was aimed at studying the specific humoral responses against SARS-CoV-2 in Cuban COVID-19 convalescents. We developed suitable tools and methods based on ELISA methodology, for supporting this evaluation. Here, we describe the development of an ELISA for the quantification of anti-RBD IgG titers in a large number of samples and a similar test in the presence of NH4SCN as chaotropic agent for estimating the RBD specific antibody avidity. Additionally, a simple and rapid ELISA based on antibody-mediated blockage of the binding RBD-ACE2 was implemented for detecting, as a surrogate of conventional test, the levels of anti-RBD inhibitory antibodies in convalescent sera. In a cohort of 273 unvaccinated convalescents, we identified higher anti-RBD IgG titer (1 : 1,330, p < 0.0001) and higher levels of inhibitory antibodies blocking RBD-ACE2 binding (1 : 216, p < 0.05) among those who had recovered from severe illness. Our results suggest that disease severity, and not demographic features such as age, sex, and skin color, is the main determinant of the magnitude and neutralizing ability of the anti-RBD antibody response. An additional paired longitudinal assessment in 14 symptomatic convalescents revealed a decline in the antiviral antibody response and the persistence of neutralizing antibodies for at least 4 months after the onset of symptoms. Overall, SARS-CoV-2 infection elicits different levels of antibody response according to disease severity that declines over time and can be monitored using our homemade serological assays.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Ensaio de Imunoadsorção Enzimática , Imunidade Humoral , Imunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Cuba , Masculino , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pessoa de Meia-Idade , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Idoso , Enzima de Conversão de Angiotensina 2/metabolismo , Afinidade de Anticorpos/imunologiaRESUMO
Background: Humoral bactericidal activity was first recognized nearly a century ago. However, the extent of inter-individual heterogeneity and the mechanisms underlying such heterogeneity beyond antibody or complement systems have not been well studied. Methods: The plasma bactericidal activity of five healthy volunteers were tested against 30 strains of Gram-negative uropathogens, Klebsiella pneumoniae and Escherichia coli, associated with bloodstream infections. IgG and IgM titers specific to K. pneumoniae strains KP13883 and KPB1 were measured by ELISA, and complement inhibitor was used to measure the contribution of complement-induced killing. Furthermore, MALDI-TOF mass spectrometry was conducted to determine the metabolomic components of plasma with bactericidal properties in 25 healthy individuals using Bayesian inference of Pearson correlation between peak intensity and colony counts of surviving bacteria. Results: Plasma bactericidal activity varied widely between individuals against various bacterial strains. While individual plasma with higher IgM titers specific to K. pneumoniae strain KP13883 showed more efficient killing of the strain, both IgM and IgG titers for K. pneumoniae strain KPB1 did not correlate well with the killing activity. Complement inhibition assays elucidated that the complement-mediated killing was not responsible for the inter-individual heterogeneity in either isolate. Subsequently, using MALDI-TOF mass spectrometry on plasmas of 25 healthy individuals, we identified several small molecules including gangliosides, pediocins, or saponins as candidates that showed negative correlation between peak intensities and colony forming units of the test bacteria. Conclusion: This is the first study to demonstrate the inter-individual heterogeneity of constitutive innate humoral bactericidal function quantitatively and that the heterogeneity can be independent of antibody or the complement system.
Assuntos
Anticorpos Antibacterianos , Proteínas do Sistema Complemento , Imunidade Humoral , Imunoglobulina G , Imunoglobulina M , Klebsiella pneumoniae , Humanos , Proteínas do Sistema Complemento/imunologia , Imunoglobulina M/imunologia , Imunoglobulina M/sangue , Klebsiella pneumoniae/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue/imunologia , Adulto , Masculino , Feminino , Escherichia coli/imunologia , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.
Assuntos
Anticorpos Anti-Hepatite , Vírus da Hepatite E , Hepatite E , Imunoglobulina M , Transplante de Fígado , Humanos , Hepatite E/epidemiologia , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Incidência , Estudos Retrospectivos , Adulto , China/epidemiologia , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Imunoglobulina M/sangue , RNA Viral/sangue , Imunoglobulina G/sangue , Transplantados/estatística & dados numéricos , Adulto Jovem , Idoso , Adolescente , PrevalênciaRESUMO
Effective treatment and immunoprophylaxis of viral respiratory infections with neutralizing monoclonal antibodies (mAbs) require maintaining inhibitory concentrations of mAbs at the airway surface. While engineered mAbs with increased affinity to the neonatal Fc receptor (FcRn) are increasingly employed, little is known how increased affinity of Fc to FcRn influences basal-to-apical transepithelial transport (transcytosis) of mAbs across the airway epithelium. To investigate this, we utilized a model of well-differentiated human airway epithelium (WD-HAE) that exhibited robust FcRn expression, and measured the transepithelial transport of a mAb against SARS-CoV-2 Spike protein (CR3022) with either wildtype IgG1-Fc or Fc modified with YTE or LS mutations known to increase affinity for FcRn. Despite the marked differences in the affinity of these CR3022 variants for FcRn, we did not find substantial differences in basal-to-apical transport reflective of systemic dosing, or apical-to-basal transport reflective of inhaled dosing, compared to the transport of wildtype IgG1-Fc. These results suggest increasing FcRn affinity may only have limited influence over transcytosis rates of systemically dosed mAbs across the human airway epithelium over short time scales. Over longer time scales, the elevated circulating levels of mAbs with greater FcRn affinity, due to more effective FcRn-mediated recycling, may better resupply mAb into the respiratory tract, leading to more effective extended immunoprophylaxis.
Assuntos
Anticorpos Monoclonais , Antígenos de Histocompatibilidade Classe I , Imunoglobulina G , Receptores Fc , Mucosa Respiratória , Transcitose , Humanos , Receptores Fc/metabolismo , Receptores Fc/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia , Imunoglobulina G/imunologia , Anticorpos Monoclonais/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , COVID-19/prevenção & controleAssuntos
Anticorpos Monoclonais Humanizados , Aquaporina 4 , Imunoglobulina G , Vacinas Meningocócicas , Neuromielite Óptica , Humanos , Aquaporina 4/imunologia , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Adulto , MasculinoAssuntos
Doença Relacionada a Imunoglobulina G4 , Pseudotumor Orbitário , Humanos , Masculino , Pseudotumor Orbitário/diagnóstico , Pseudotumor Orbitário/imunologia , Pseudotumor Orbitário/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/imunologia , Doença Relacionada a Imunoglobulina G4/complicações , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/imunologia , Neoplasias da Mama Masculina/diagnóstico , Resultado do Tratamento , Imunoglobulina G/sangue , Pessoa de Meia-Idade , BiópsiaRESUMO
Pemphigus is an IgG-mediated autoimmune condition characterized by autoantibodies targeting desmogleins, leading to acantholysis. Current treatments, including systemic corticosteroids and immunosuppressive drugs, are associated with significant adverse effects. Mesenchymal stem cells (MSCs) offer a promising alternative due to their immunomodulatory properties and low immunogenicity. This study evaluates the immunomodulatory effects of dental follicle mesenchymal stem cells (DF-MSCs) obtained from healthy donors on Pemphigus vulgaris (PV) patients and healthy controls by examining T-cell proliferation, apoptosis, cytokine levels, and anti-desmoglein 1/3 IgG profiles. Peripheral blood mononuclear cells (PBMCs) were isolated from twenty-one symptomatic PV patients and eleven healthy volunteers. DF-MSCs were characterized and differentiated into osteocytes, adipocytes, and chondrocytes. Peripheral blood mononuclear cells (PBMCs) were co-cultured with DF-MSCs, and various assays were conducted to evaluate T-cell proliferation, apoptosis, regulatory T cells, cytokine expression, and autoantibody levels. Results showed that DF-MSC co-cultures significantly reduced lymphocyte proliferation (43.58-16.27%), IL-4 (38.06 ng/L to 32.26 ng/L), TNF-α (32.45 ng/L to 29.41 ng/L), and DSG1 (3.29 ng/ml to 3.00 ng/ml) and DSG3 (262.40 ng/ml to 245.08 ng/ml) levels in PV patients. An increase in regulatory T cells (1.22-3.75%), IL-10 (47.46 pg/ml to 54.94 pg/ml), and IFN-γ (12.39 ng/ml to 19.70 ng/ml) was also observed. No significant changes were noted in healthy controls. These findings suggest that DF-MSCs could potentially offer a curative approach for treating pemphigus by restoring immune balance. However, further clinical trials are necessary to confirm their efficacy.
Assuntos
Autoanticorpos , Proliferação de Células , Células-Tronco Mesenquimais , Pênfigo , Humanos , Pênfigo/imunologia , Pênfigo/terapia , Pênfigo/sangue , Células-Tronco Mesenquimais/imunologia , Feminino , Masculino , Autoanticorpos/sangue , Autoanticorpos/imunologia , Adulto , Técnicas de Cocultura , Desmogleína 3/imunologia , Apoptose/imunologia , Saco Dentário/imunologia , Células Cultivadas , Citocinas/metabolismo , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Diferenciação Celular/imunologia , Desmogleína 1/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos T Reguladores/imunologia , Estudos de Casos e ControlesRESUMO
Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Infecções por Papillomavirus , Humanos , China/epidemiologia , Estudos Soroepidemiológicos , Masculino , Feminino , Anticorpos Antivirais/sangue , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Adulto , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Adulto Jovem , Idoso , Adolescente , Criança , Imunoglobulina G/sangue , Pré-Escolar , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Papillomaviridae/imunologia , Papillomaviridae/genética , Papillomaviridae/classificação , Testes de Neutralização , Vacinação/estatística & dados numéricos , Idoso de 80 Anos ou mais , Lactente , Papillomavirus HumanoRESUMO
OBJECTIVE: To study the relationship of the parameters of immunity and systemic inflammation with the structural magnetic resonance imaging (MRI) parameters in patients with mild cognitive impairment (MCI) and pre-MCI undergoing neurocognitive rehabilitation to search for candidate markers of its effectiveness. MATERIAL AND METHODS: The main group included 49 patients, aged ≥60 years, with MCI and pre-MCI with memory impairment, who underwent a course of neurorehabilitation for 5 weeks. The control group included 19 volunteers of similar age with a total MoCA score of ≥25, who did not have cognitive impairment and immuno-inflammatory disorders. The parameters of cellular and humoral immunity and markers of inflammation were studied, and structural MRI was performed. RESULTS: The content of activated natural killer cells (NK-cells) was increased in MCI and pre-MCI (0.63±0.12% vs. 0.22±0.07% in the control group, p=2.2·10-7). The level of immunoglobulin G (IgG) <12.5 g/l in patients with MCI and pre-MCI with the Montreal Cognitive Assessment Scale (MoCA) score <22 was associated with a decrease in the volume of the right nucleus accumbens (376±35 mm3 in patients with IgG <12.5 g/l (p=0.0013) and 480±44 mm3 at IgG <12.5 g/l, 480±44 mm3 in the control group), as well as with a decrease of the thickness and volume of a number of other cortical zones. A logistic regression model including the level of immunoglobulin G, NK cells, CD8+ NK cells and right amygdala volume was constructed to predict the number of MoCA scores 6 months after the course of rehabilitation (R2=0.57; p<1·10-5; standard error of estimate: 2.93). CONCLUSION: As a result of this work, the perspectives of assessing the immunological parameters in combination with socio-demographic data and morphometric changes of the brain as potential prognostic markers of the dynamics of cognitive impairment in patients with MCI and pre-MCI after neurorehabilitation has been shown.
Assuntos
Biomarcadores , Disfunção Cognitiva , Células Matadoras Naturais , Imageamento por Ressonância Magnética , Humanos , Disfunção Cognitiva/imunologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Células Matadoras Naturais/imunologia , Imunoglobulina G/sangue , Inflamação/imunologiaRESUMO
BACKGROUND: The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. OBJECTIVES: To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. METHODS: Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. FINDINGS: Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. MAIN CONCLUSIONS: The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Citocinas , Pessoal de Saúde , Imunização Secundária , Imunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Masculino , Feminino , Anticorpos Antivirais/sangue , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pessoa de Meia-Idade , Citocinas/imunologia , Citocinas/sangue , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina A/análise , Vacinação , Adulto Jovem , Imunidade Humoral/imunologia , Vacinas de Produtos InativadosRESUMO
BACKGROUND: HEV is endemic in several Middle Eastern countries including Saudi Arabia, which hosts the annual pilgrimage for Muslims from around the world. One of the Hajj rituals is the sacrifice of animals, including camels, cows, goats, and sheep. HEV Zoonosis is established in swine and other suspected species, including deer, rabbits, dromedary, and Bactrian camels. HEV was identified in small, domesticized animals like goats, cows, sheep, and horses. We previously investigated HEV seroprevalence in Camels. This study aimed to evaluate HEV seroprevalence in other highly consumed ruminants in Saudi Arabia, namely cows, sheep, and goats. METHODS: Sera from cows (n = 47), goats (n = 56), and sheep (n = 67) were analyzed for the presence of HEV-IgG by using in-house developed ELISA assays. RESULTS: The highest seroprevalence was found in sheep (62.7%), followed by cows (38.3%), and then goats (14.3%), with a p-value of < 0.001. No other demographic characteristics of the animals were significantly correlated with the HEV seroprevalence. CONCLUSIONS: This study provides baseline data as the first study on the seroprevalence of HEV in ruminant animals in Saudi Arabia. The high seroprevalence found in sheep and cows must be further investigated for the potential zoonotic HEV transmission to humans. Further studies are needed to investigate the active viremia in these animal species through nucleic acid detection and sequencing to provide data on the circulating HEV genotypes among the targeted animal species. The detection of HEV in different animal products, such as milk, liver, and others, also remains an important study area to consider.
Assuntos
Cabras , Vírus da Hepatite E , Hepatite E , Ruminantes , Animais , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/isolamento & purificação , Hepatite E/epidemiologia , Hepatite E/veterinária , Hepatite E/virologia , Estudos Soroepidemiológicos , Cabras/virologia , Ovinos , Arábia Saudita/epidemiologia , Bovinos , Ruminantes/virologia , Feminino , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G/sangue , Zoonoses/virologia , Zoonoses/epidemiologia , Zoonoses/diagnóstico , Anticorpos Anti-Hepatite/sangue , Doenças das Cabras/virologia , Doenças das Cabras/epidemiologia , Doenças das Cabras/diagnóstico , Doenças das Cabras/sangue , MasculinoRESUMO
BACKGROUND: Pregnancy is a critical time for women, making them more susceptible to infectious diseases like COVID-19. This study aims to determine the immunogenicity of COVID-19 in pregnant women who have been infected compared to those who have received the inactive COVID-19 vaccine. MATERIALS AND METHODS: In this retrospective cohort study, pregnant women who received the inactivated COVID-19 vaccine (Sinopharm) and those with a history of COVID-19 infection during pregnancy were studied. Participants who had experienced stillbirth, received different COVID-19 vaccines, or had intrauterine fetal death were excluded from the study. Overall, the study included 140 participants. The participants were divided into two groups of 70 participants - pregnant women who received the Sinopharm vaccine and pregnant women who had COVID-19 infection during pregnancy. Before delivery, blood samples were collected from all mothers to evaluate the maternal immunoglobulin G (IgG) level. Blood samples were also taken from the baby's umbilical cord during delivery to measure the newborn's IgG level. Additionally, blood samples were collected from babies whose mothers showed signs of acute infection to measure their IgM levels and evaluate vertical transmission. FINDINGS: The study found a significant relationship between the mean level of maternal IgG and umbilical cord IgG within the groups (P < 0.001). The highest levels of maternal IgG (2.50 ± 2.17) and umbilical cord IgG (2.43 ± 2.09) were observed in pregnant women with a previous COVID-19 infection and no history of vaccination (P < 0.001). Only one baby was born with a positive IgM, and this baby was born to a mother who showed signs of COVID-19 infection in the last five days of pregnancy. The mother was 28 years old, with a BMI of 33; it was her first pregnancy, and she gave birth to a male newborn at term. CONCLUSION: Administering an inactivated vaccine during pregnancy can generate immunity in both the mother and the child. However, the vaccine's immunity level may not be as potent as that conferred by COVID-19 infection during pregnancy. Nonetheless, the risk of vertical transmission of COVID-19 is considered minimal and can be classified as negligible.
Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunoglobulina G , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , Gravidez , Feminino , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Estudos Retrospectivos , Imunoglobulina G/sangue , Adulto , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Vacinação , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Recém-Nascido , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Gestantes , Imunogenicidade da VacinaRESUMO
BACKGROUND: Herpes simplex virus type 1 (HSV-1) is a major cause of viral encephalitis, genital mucosal infections, and neonatal infections. Lactococcus lactis (L. lactis) has been proven to be an effective vehicle for delivering protein antigens and stimulating both mucosal and systemic immune responses. In this study, we constructed a recombinant L. lactis system expressing the protective antigen glycoprotein D (gD) of HSV-1. RESULTS: To improve the stability and persistence of antigen stimulation of the local mucosa, we inserted the immunologic adjuvant interleukin (IL)-2 and the Fc fragment of IgG into the expression system, and a recombinant L. lactis named NZ3900-gD-IL-2-Fc was constructed. By utilizing this recombinant L. lactis strain to elicit an immune response and evaluate the protective effect in mice, the recombinant L. lactis vaccine induced a significant increase in specific neutralizing antibodies, IgG, IgA, interferon-γ, and IL-4 levels in the serum of mice. Furthermore, in comparison to the mice in the control group, the vaccine also enhanced the proliferation levels of lymphocytes in response to gD. Moreover, recombinant L. lactis expressing gD significantly boosted nonspecific immune reactions in mice through the activation of immune-related genes. Furthermore, following the HSV-1 challenge of the murine lung mucosa, mice inoculated with the experimental vaccine exhibited less lung damage than control mice. CONCLUSION: Our study presents a novel method for constructing a recombinant vaccine using the food-grade, non-pathogenic, and non-commercial bacterium L. lactis. The findings indicate that this recombinant vaccine shows promise in preventing HSV-1 infection in mice.
Assuntos
Herpes Simples , Herpesvirus Humano 1 , Lactococcus lactis , Camundongos Endogâmicos BALB C , Lactococcus lactis/genética , Animais , Camundongos , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/genética , Herpes Simples/prevenção & controle , Herpes Simples/imunologia , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas Sintéticas/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologiaRESUMO
RATIONALE: Eczematous external otitis (EEO) is the most difficult-to-treat otitis externa, and characterized by the symptoms of inflammation with hypersensitivity of the external ear canal skin. It is acknowledged as a chronic skin inflammation primarily caused by dermatological and allergic reactions. Food allergens are also considered a cause to induce the inflammation. However, the role of food specific IgG4 in this disease is unclear yet. PATIENT CONCERNS: A 54-year-old woman complained of recurrent itching of the external auditory meatus for 3 years and nails chapping of hands for 2 years. DIAGNOSES AND INTERVENTIONS: She was diagnosed with EEO and underwent the therapeutic strategy as food elimination of egg, milk and wheat, guided by the result of food specific IgG4 together with probiotics on the basis of previous symptom controlling therapy. OUTCOMES: After 17 months' treatment, she was finally free of all the symptoms and the serum IgG4 specific to all foods are under normal limit. LESSONS: To the best of our knowledge, it is the first report revealing the clinical significance of food specific IgG4 in EEO, and the successful treatment with diet elimination guided by food specific IgG4 threw a new light on the clinical management of refractory EEO.
Assuntos
Hipersensibilidade Alimentar , Imunoglobulina G , Otite Externa , Humanos , Feminino , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/imunologia , Otite Externa/tratamento farmacológico , Eczema/dietoterapia , Probióticos/administração & dosagem , Probióticos/uso terapêuticoRESUMO
Elevated numbers of antibody-secreting cells (ASCs) and anti-double-stranded DNA (anti-dsDNA) antibodies are found in nasal polyp (NP) tissue. The presence of anti-dsDNA IgG in tissue prospectively predicts recurrent NP but the characteristics of the source ASCs are unknown. Here, we investigated whether NP B cells expressing the extrafollicular marker EBI2 have increased propensity for autoantibody production and evaluated the molecular characteristics of NP ASCs. NPs showed increased frequencies of anti-dsDNA IgG and total IgG ASCs compared with tonsils, with more pronounced differences among EBI2+ cells. In NPs, EBI2+ cells were frequently double negative (IgD-CD27-) and ASCs. Single-cell RNA-Seq analysis of tonsils and NPs revealed substantial differences in B lineage composition, including differences in percentages of ASCs, germinal centers, proliferative cells, and non-ASCs. NPs exhibited higher expression of specific isotypes (IGHE, IGHA1, IGHA2, and IGHG4) and mature plasma genes, including SDC1 and XBP1, than tonsils. Gene Ontology biological processes indicated upregulated NF-κB and downregulated apoptosis pathways in NP ASCs. Together, these data indicate that NP EBI2+ ASCs secret increased total and anti-dsDNA IgG compared with those from tonsils and had molecular features of mature plasma cell differentiation.
Assuntos
Células Produtoras de Anticorpos , Imunoglobulina G , Pólipos Nasais , Humanos , Pólipos Nasais/imunologia , Pólipos Nasais/patologia , Pólipos Nasais/metabolismo , Células Produtoras de Anticorpos/imunologia , Células Produtoras de Anticorpos/metabolismo , Masculino , Feminino , Adulto , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Pessoa de Meia-Idade , Tonsila Palatina/imunologia , Tonsila Palatina/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Antígenos de Histocompatibilidade Menor/imunologia , Anticorpos Antinucleares/imunologia , Idoso , Adulto JovemRESUMO
BACKGROUND: B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide is the only blood biomarker in established risk calculators for pulmonary arterial hypertension (PAH). Profiling systemic-originated plasma immunoglobulin G (IgG) N-glycans, which reflect different components of the pathophysiology of PAH including immune dysregulation and inflammation, may improve PAH risk assessment. OBJECTIVES: This study sought to identify plasma IgG N-glycan biomarkers that predict survival in PAH to improve risk assessment. METHODS: This cohort study examined 622 PAH patients from 2 national centers (Beijing [discovery] cohort: n = 273; Shanghai [validation] cohort: n = 349). Plasma IgG N-glycomes were profiled by a robust mass spectrometry-based method. Prognostic IgG N-glycan traits were identified and validated in the 2 cohorts using Cox regression and Kaplan-Meier survival analyses. The added value of IgG N-glycan traits to previously established risk models was assessed using Harrell C-indexes and survival analysis. RESULTS: Plasma IgG fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377; 95% CI: 0.168-0.845; P = 0.018) with confirmation in the validation cohort (HR: 0.445; 95% CI: 0.264-0.751; P = 0.005). IgG fucosylation remained a robust predictor of mortality in combined cohorts after full adjustment and in subgroup analyses. Integrating IgG fucosylation into previously established risk models improved their predictive capacity, marked by an overall elevation in Harrell C-indexes. IgG fucosylation was useful in further stratifying the intermediate-risk patients classified by a previously established model. CONCLUSIONS: Plasma IgG fucosylation informs PAH prognosis independent of established factors, offering additional value for predicting PAH outcomes.
Assuntos
Biomarcadores , Imunoglobulina G , Humanos , Feminino , Masculino , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Prognóstico , Biomarcadores/sangue , Adulto , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/mortalidade , Estudos de Coortes , Polissacarídeos/sangue , Idoso , Medição de Risco/métodos , China/epidemiologiaRESUMO
Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcµR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.
Assuntos
Plaquetas , COVID-19 , Ativação do Complemento , Imunoglobulina M , Trombose , Humanos , Trombose/imunologia , Animais , Imunoglobulina M/imunologia , Ativação do Complemento/imunologia , Camundongos , Plaquetas/imunologia , Plaquetas/metabolismo , COVID-19/imunologia , COVID-19/complicações , SARS-CoV-2/imunologia , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Ativação Plaquetária/imunologia , Imunoglobulina G/imunologia , MasculinoRESUMO
SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal-Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.
Assuntos
Anticorpos Antivirais , COVID-19 , Convalescença , Citocinas , Imunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Citocinas/sangue , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Estudos Longitudinais , Idoso , Eosinófilos/imunologia , Eosinófilos/metabolismoRESUMO
BACKGROUND: To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. CASE PRESENTATION: A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. CONCLUSIONS: This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.