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1.
BMC Vet Res ; 20(1): 170, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702674

RESUMO

BACKGROUND: Blood sampling from neonatal piglets is related to multiple disadvantages. Therefore, a new, alternative matrix is required to assess piglets' early immune status efficiently. The present study aimed to assess the usefulness of processing fluid for determining selected piglets' immune parameters. 264 pigs - 31 sows, 146 male piglets, and 87 female piglets from commercial indoor farrow-to-finish pig herd were included in this study. 264 serum, 31 colostrum, and 146 processing fluid samples were collected. Serum was collected from all animals, colostrum was collected from sows, and processing fluid was collected from male piglets only. Using commercial ELISA tests, the concentration of various immunoglobulins, cytokines, and acute phase proteins was assessed in each matrix. Statistical analyses were employed to determine differences in the concentration of measured indices between piglets' serum and processing fluid and correlations in the concentration of tested indices between particular sets of matrices. RESULTS: Statistical analyses did not reveal significant differences in the IgG, IgA, IL-1ß, IL-4, IL-6, and IFN-γ concentration between piglets' serum and processing fluid (p > 0.05). A positive correlation (p < 0.05) regarding the concentration of some indices between processing fluid and samples collected from sows was also observed. CONCLUSIONS: Processing fluid can be considered a promising alternative to blood for assessing some immunological indices in piglets, such as IgG, IgA, IL-1ß, IL-4, IL-6, and IFN-γ, and, possibly, in the indirect assessment of some indices in lactating sows, including IgA, IL-1ß, IL-4, IL-6, IL-8, IFN-γ, or Pig-MAP.


Assuntos
Colostro , Citocinas , Imunoglobulinas , Animais , Colostro/química , Colostro/imunologia , Feminino , Masculino , Suínos/sangue , Citocinas/sangue , Citocinas/análise , Imunoglobulinas/sangue , Imunoglobulinas/análise , Animais Recém-Nascidos/imunologia , Animais Recém-Nascidos/sangue , Animais Lactentes/imunologia , Animais Lactentes/sangue , Proteínas de Fase Aguda/análise , Proteínas de Fase Aguda/metabolismo
2.
Front Immunol ; 15: 1374535, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707898

RESUMO

Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection. Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time. Results: The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871-1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144-1.160, P-value<0.001). Discussion: The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Fatores de Tempo , Imunoglobulinas/sangue , Fatores de Risco , Agamaglobulinemia/sangue , Agamaglobulinemia/imunologia , Agamaglobulinemia/etiologia , Biomarcadores/sangue , Infecções/etiologia , Infecções/imunologia , Infecções/sangue , Infecções/epidemiologia
3.
Anim Sci J ; 95(1): e13946, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651265

RESUMO

This study explored the effects of a Bacillus subtilis and Lactobacillus acidophilus mixture containing the co-fermented products of the two probiotics on growth performance, serum immunity and cecal microbiota of Cherry Valley ducks. This study included 480 one-day-old Cherry Valley ducks divided into four feeding groups: basal diet (control group) and basal diet supplemented with 300, 500, or 700 mg/kg of the probiotic powder; the ducks were raised for 42 days. Compared with the control group, body weight on day 42 and the average daily gain on days 15-42 significantly increased (p < 0.05), and the feed conversion rate significantly decreased (p < 0.05) in the experimental groups. Furthermore, the serum immunoglobulin (Ig) A, IgG, IgM, and interleukin (IL)-4 levels increased significantly (p < 0.05), and IL-1ß, IL-2, and tumor necrosis factor-α decreased significantly (p < 0.05) in the experimental groups. Finally, Sellimonas, Prevotellaceae NK3B31 group, Lachnospiraceae NK4A136 group and Butyricoccus played an important role in the cecal microbiota of the experimental group. Thus, the probiotic powder has impacts on the growth performance, serum immunity and cecal microbiota of Cherry Valley Ducks.


Assuntos
Bacillus subtilis , Ceco , Patos , Lactobacillus acidophilus , Probióticos , Animais , Probióticos/administração & dosagem , Ceco/microbiologia , Patos/crescimento & desenvolvimento , Patos/microbiologia , Patos/imunologia , Patos/sangue , Microbioma Gastrointestinal , Dieta/veterinária , Ração Animal , Imunoglobulinas/sangue , Suplementos Nutricionais
5.
Scand J Immunol ; 99(6): e13368, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38527944

RESUMO

Cellular debris resulting from large trauma might overwhelm the scavenger mechanisms and lead to autoimmune reactions. We analysed whether a major well-defined trauma in humans induces laboratory signs of transient autoimmunity in the months after the insult. We included 50 patients with pertrochanteric femur fracture undergoing intramedullary nail osteosynthesis in a prospective cohort study and followed them at 3-4 days, 6 weeks, 12 weeks and 12 months postoperatively. By standard techniques, we assessed levels of total immunoglobulins, anti-nuclear antibodies (ANA), anti-cardiolipin antibodies, anti-dsDNA antibodies and anti-C1q antibodies, as well as antibodies against cytomegalovirus (CMV) as a control. Blood leukocyte differential and lymphocyte subpopulations were determined at baseline and in the first two postoperative samples. The mean age of the patients reached 80.1 years, and 23 (46%) completed all visits. Serum concentrations of total IgG, IgM and IgA increased at all follow-up time points. The ANA fluorescence light intensity units increased at 12 weeks and 12 months postoperatively (p < 0.0001), but the proportion of ANA-positive patients did not change (35%). The values of anti-C1q mildly increased at all follow-up visits, but not the ratio to total IgG. Anti-dsDNA remained negative in all patients, and anti-cardiolipin IgG/IgM antibodies did not change. Anti-CMV IgG antibodies increased significantly at all follow-up visits, without change in the ratio to total IgG. Flow cytometry showed an increased proportion of B-cells 3-4 days postoperatively. In conclusion, major musculoskeletal trauma in elderly patients induces a generalized non-specific increase in immunoglobulin production without laboratory signs for enhanced systemic autoimmunity.


Assuntos
Autoanticorpos , Humanos , Masculino , Feminino , Estudos Prospectivos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Complemento C1q/imunologia , Imunoglobulina M/sangue , Estudos de Coortes , Autoimunidade , Imunoglobulinas/sangue
6.
Elife ; 122023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127423

RESUMO

Germline CTLA-4 deficiency causes severe autoimmune diseases characterized by dysregulation of Foxp3+ Tregs, hyper-activation of effector memory T cells, and variable forms autoimmune cytopenia including gradual loss of B cells. Cancer patients with severe immune-related adverse events (irAE) after receiving anti-CTLA-4/PD-1 combination immunotherapy also have markedly reduced peripheral B cells. The immunological basis for B cell loss remains unexplained. Here, we probe the decline of B cells in human CTLA-4 knock-in mice by using anti-human CTLA-4 antibody Ipilimumab conjugated to a drug payload emtansine (Anti-CTLA-4 ADC). The anti-CTLA-4 ADC-treated mice have T cell hyper-proliferation and their differentiation into effector cells which results in B cell depletion. B cell depletion is mediated by both CD4 and CD8 T cells and at least partially rescued by anti-TNF-alpha antibody. These data revealed an unexpected antagonism between T and B cells and the importance of regulatory T cells in preserving B cells.


Assuntos
Abatacepte , Linfócitos B , Linfócitos T Reguladores , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Abatacepte/farmacologia , Animais , Camundongos , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Depleção Linfocítica , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Apoptose/efeitos dos fármacos , Imunoglobulinas/sangue , Imunoglobulinas/imunologia , Células CHO , Cricetulus , Camundongos Endogâmicos C57BL , Masculino , Feminino
7.
JAMA ; 330(12): 1167-1174, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37750879

RESUMO

Importance: While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. Objective: To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Design, Setting, and Participants: Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Exposure: Induced first-trimester abortion. Main Outcomes and Measures: The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Results: Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Conclusions and Relevance: Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.


Assuntos
Aborto Induzido , Eritrócitos , Isoimunização Rh , Adulto , Feminino , Humanos , Gravidez , Aborto Induzido/métodos , Imunoglobulinas/sangue , Estudos Prospectivos , Isoimunização Rh/diagnóstico , Isoimunização Rh/imunologia , Isoimunização Rh/terapia , Risco , Primeiro Trimestre da Gravidez/imunologia , Eritrócitos/imunologia , Adulto Jovem , Negro ou Afro-Americano , Brancos
8.
Int J Mol Sci ; 24(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37511357

RESUMO

Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively). Our results revealed that patients with supposed circulating CGs displayed a pattern of serological parameters that closely resembled Cryo II and Cryo III, with a stronger similarity to Cryo II. Accordingly, we analyzed the groups of Circulating and Cryo II for their immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements, finding a similar mixed distribution of monoclonal, oligoclonal, and polyclonal responses compared to a control group of ten HCV-RNA-negative patients recovered from infection, who displayed a 100% polyclonal response. Our results strengthened the hypothesis that circulating CGs are the origin of symptoms in HCV-RNA-positive patients without cryoprecipitate and demonstrated that an analysis of clonal IGH and TCR rearrangements is the best option for the early diagnosis of extrahepatic complications.


Assuntos
Crioglobulinemia , Crioglobulinas , Hepatite C Crônica , Vasculite , Vasculite/diagnóstico , Vasculite/imunologia , Vasculite/virologia , Humanos , Masculino , Feminino , Crioglobulinemia/diagnóstico , Crioglobulinemia/virologia , Crioglobulinas/análise , Fator Reumatoide/sangue , Imunoglobulinas/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações
9.
Int Immunol ; 35(5): 243-253, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36591893

RESUMO

Immunogenicity can be evaluated by detecting antibodies (Abs) induced by an antigen. Presently deployed assays, however, do not consider the negative impacts of Ab poly-specificity, which is well established at the monoclonal antibody level. Here, we studied antibody poly-specificity at the serum level (i.e. nonspecific Ab-probe interactions, NSIs), and ended up establishing a new platform for viral peptide immunogenicity evaluation. We first selected three peptides of high, medium and low immunogenicity, using a 'vaccine serum response rate'-based approach (i.e. the gold standard). These three peptides (Pi) in the bovine serum albumin-Pi form were used to immunize chickens, resulting in longitudinal serum samples for screening with a non-cognate peptide library. The signal intensity of Ab-peptide specific binding and 'NSI count' was used to evaluate the viral peptides' immunogenicity. Only the NSI count agreed with the gold standard. The NSI count also provides more informative data on antibody production than the aggregated signal intensity by whole-protein-based indirect enzyme-linked immunosorbent assay.


Assuntos
Especificidade de Anticorpos , Imunoglobulinas , Peptídeos , Proteínas Virais , Biblioteca de Peptídeos , Imunoglobulinas/sangue , Animais , Galinhas , Vírus da Doença de Newcastle/imunologia , Peptídeos/imunologia , Ensaio de Imunoadsorção Enzimática , Formação de Anticorpos , Proteínas Virais/imunologia
10.
Allergol. immunopatol ; 51(4): 151-157, 2023. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-222645

RESUMO

Background and aim: Bronchial asthma is a prevalent type of respiratory disease that affects a large proportion of pediatric patients. The purpose of this study is to further investigate the clinical effects of budesonide combined with montelukast sodium in treating bronchial asthma. Methods: Eighty-six children with bronchial asthma were equally divided into study and control groups via randomized double-blind controlled trial. The control group was treated with aerosol inhalation of budesonide combined with placebo, while the study group was treated with budesonide combined with montelukast sodium. Pulmonary function parameters, immunoglobulin, and recovery of related symptoms, along with the adverse reaction rate, were observed and compared between both groups. Results: Before treatment, there was no marked difference in pulmonary function parameters and immunoglobulin indexes between both groups (P > 0.05). All pulmonary function indicators and immunoglobulin indexes in both groups improved following therapy, with the study group outperforming the control group (P < 0.05). The recovery time of related symptoms in the study group was shorter than that in the control group (P < 0.05). The incidence of adverse reactions in both groups was compared, with notable differences (P < 0.05). Conclusion: Budesonide combined with montelukast sodium in the treatment of bronchial asthma has the value of clinical application and promotion (AU)


Assuntos
Humanos , Pré-Escolar , Criança , Budesonida/administração & dosagem , Broncodilatadores/administração & dosagem , Asma/tratamento farmacológico , Imunoglobulinas/sangue , Antiasmáticos/administração & dosagem , Antagonistas de Leucotrienos/administração & dosagem , Citocromo P-450 CYP1A2/administração & dosagem , Quimioterapia Combinada , Resultado do Tratamento
11.
J Immunother Cancer ; 10(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35091456

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICI) are a novel cancer therapeutic that have been successful in treating advanced malignancies; however, they also cause immune-related adverse events (irAE). Given that some irAE are clinically similar to traditional autoimmune diseases, autoantibodies have been suggested as possible biomarkers of irAE. However, there are very little data on autoantibody investigation prior to ICI. Our aim was to determine if specific baseline autoantibodies were associated with irAE and see if changes in autoantibody concentration corresponded with irAE development. METHODS: This study used data from an oncologic clinical trial of adaptive dosing combination ICI therapy in patients with advanced melanoma. Plasma was collected at baseline and 6 weeks after ICI initiation and tested in a microarray of 120 autoantigens commonly associated with autoimmune disease, as well as antinuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (anti-CCP). Autoantibody concentrations were compared between patients experiencing an organ-specific event versus not. Heatmaps, volcano plots and hierarchical clustering were used to determine autoantibody concentration differences among irAE patient clusters as defined by signal intensity of autoantibodies. Kaplan-Meier curves were created and a log-rank test was performed to assess differences in survival. RESULTS: The microarray analysis demonstrated that patients who experienced specific irAE had fewer differentially expressed autoantibodies at baseline than those that did not have those specific irAE, and a greater fold change (FC) in antibody concentration from baseline to 6 weeks corresponded with specific irAE development. However, no autoantibodies were identified as being predictive of specific events. Time to first irAE was less than 6 weeks in 69% of patients, and these patients had less autoantibodies at baseline. Considering ANA, RF and CCP autoantibodies, there were no significant differences between the seropositive and seronegative patients in irAE development, severity, timing or survival. CONCLUSION: Patients with low autoantibody concentrations at baseline as well as a greater FC in autoantibody concentration over 6 weeks developed more distinct organ-specific irAE. This may suggest differences in the balance of cellular immunity and humoral pathways that are relevant in the pathogenesis of irAE, though further investigation is needed.


Assuntos
Autoanticorpos/sangue , Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/tratamento farmacológico , Idoso , Anticorpos Antiproteína Citrulinada/sangue , Anticorpos Antinucleares/sangue , Feminino , Humanos , Imunoglobulinas/sangue , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Fator Reumatoide/sangue
12.
J Nutr Biochem ; 101: 108947, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35017006

RESUMO

In this study, cyclophosphamide (Cy) was used to treat mice to establish an immunosuppressant model in mice, and the regulatory effects of polysaccharides from Fuzhuan brick tea (FBTPSs) including crude FBTPSs (CFBTPSs) and the purified fraction (FBTPSs-3) on the immune function and gut microbiota of mice were investigated. The results showed that CFBTPSs and FBTPSs-3 restored the levels of body weight, feed intake, immune organ index, cytokine and immunoglobulin A in mice. The Cy-induced injury of gut including intestinal morphology and expression of tight junction proteins were also restored. Furthermore, CFBTPSs and FBTPSs-3 could significantly modulate gut microbiota by increasing the relative abundance of Muribaculaceae and reduceing the relative abundances of Lachnospiraceae, Helicobacteraceae, Clostridaceae, Desulfovibrionaceae and Deferribacteraceae. Moreover, the gut microbiota derived short-chain fatty acids might play an important role in improvement of immune function by FBTPSs. Our results showed that FBTPSs could regulate the immune function of mice, which provided evidences for the development of FBTPSs as potentially functional foods to improve human health.


Assuntos
Microbioma Gastrointestinal , Sistema Imunitário/fisiologia , Polissacarídeos/administração & dosagem , Chá , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Peso Corporal , Ciclofosfamida , Citocinas/biossíntese , Ingestão de Alimentos , Ácidos Graxos Voláteis/metabolismo , Alimento Funcional , Imunoglobulinas/sangue , Imunossupressores , Intestinos/metabolismo , Intestinos/microbiologia , Intestinos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Junções Íntimas/metabolismo
13.
Behav Brain Res ; 416: 113532, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34416302

RESUMO

Predation risk can program offspring behavior, physiology, and fitness through maternal effect, but most studies have mainly focused on this effect during pregnancy; little is known about the effect of postpartum predation risk on offspring's phenotype. Here, we compared the antipredator behaviors of adult offspring (approximately 90 days old) produced by female Brandt's voles (Lasiopodomys brandtii) exposed to one of three treatments: cat odor (CO), rabbit odor (RO), and distilled water (DW) for 60 min daily from postpartum day 1-18. Basal levels of plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT), hypothalamic corticotrophin releasing hormone (CRH), as well as spleen immunoglobulins (IgA, IgM, and IgG) were also measured. Our data showed that the offspring of CO-exposed mothers displayed less head-out behavior to acute 15-min CO exposure, and female offspring showed more freezing behavior. CO offspring showed significantly lower basal ACTH and CORT levels than the RO and DW offspring. Additionally, female but not male CO offspring had higher hypothalamic CRH expression and spleen IgG levels than controls, showing a sex-specific effect. These findings demonstrate that postpartum maternal predator risk exposure promotes a passive-avoidant response to these cues in adult offspring, showing a cross-generational maternal effect of postpartum predation risk. Further, these changes may be associated with alterations in the hypothalamic-pituitary-adrenal axis and immune function.


Assuntos
Arvicolinae , Imunoglobulinas/sangue , Exposição Materna , Odorantes , Período Pós-Parto/imunologia , Comportamento Predatório/fisiologia , Hormônio Adrenocorticotrópico/sangue , Animais , Arvicolinae/imunologia , Arvicolinae/fisiologia , Corticosterona/sangue , Corticosterona/fisiologia , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo
14.
Clin Immunol ; 235: 108791, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34214649

RESUMO

Coronavirus Disease 2019 (COVID-19) emerged as a global pandemic resulting in significant mortality and morbidity. COVID-19 vaccines have been shown to be highly effective in preventing COVID-19 infections and significantly reducing disease severity and mortality. We report on a novel COVID-19 antibody assay using a unique platform to rapidly detect SARS-CoV-2 antibodies with a drop of fingerstick blood in a subject following COVID-19 vaccination. We show early detection of SARS-CoV-2 antibodies post vaccination and persistence of detectable antibodies for at least 6 months. Rapid point of care COVID-19 antibody tests might have a role in assessing the appearance and durability of immune response following COVID-19 vaccination.


Assuntos
Anticorpos Antivirais/imunologia , Vacina BNT162/imunologia , Coleta de Amostras Sanguíneas/métodos , COVID-19/imunologia , Imunoglobulinas/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Vacina BNT162/administração & dosagem , COVID-19/epidemiologia , COVID-19/virologia , Teste Sorológico para COVID-19/métodos , Dedos , Humanos , Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Reprodutibilidade dos Testes , SARS-CoV-2/fisiologia , Vacinação
15.
J Allergy Clin Immunol ; 149(1): 315-326.e9, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34146579

RESUMO

BACKGROUND: Noninfectious complications are the greatest cause of morbidity and mortality in common variable immunodeficiency (CVID), but their pathogenesis remains poorly defined. OBJECTIVE: Using high-throughput approaches, we aimed to identify, correlate, and determine the significance of immunologic features of CVID with noninfectious complications (CVIDc). METHODS: We simultaneously applied proteomics, RNA sequencing, and mass cytometry to a large cohort with primary antibody deficiency. RESULTS: CVIDc is differentiated from uncomplicated CVID, other forms of primary antibody deficiency, and healthy controls by a distinct plasma proteomic profile. In addition to confirming previously reported elevations of 4-1BB, IL-6, IL-18, and IFN-γ, we found elevations of colony-stimulating factor 1, IL-12p40, IL-18R, oncostatin M, TNF, and vascular endothelial growth factor A to differentiate CVIDc. This cytokine dysregulation correlated with deficiency of LPS-specific antibodies and increased soluble CD14, suggesting microbial translocation. Indicating potential significance of reduced LPS-specific antibodies and resultant microbial-induced inflammation, CVIDc had altered LPS-induced gene expression matching plasma proteomics and corresponding with increased CD14+CD16- monocytes, memory T cells, and tissue inflammation ameliorated by T-cell-targeted therapy. Unsupervised machine learning accurately differentiated subjects with CVIDc and supported cytokine dysregulation, antibody deficit, and T-cell activation as defining and convergent features. CONCLUSIONS: Our data expand understanding of CVIDc proteomics, establish its link with deficiency of IgA and LPS-specific antibodies, and implicate altered LPS-induced gene expression and elevated monocytes and T cells in this cytokine dysregulation. This work indicates that CVIDc results when insufficient antibody neutralization of pathogen-associated molecular patterns, like LPS, occurs in those with a heightened response to these inflammatory mediators, suggesting a 2-hit model of pathogenesis requiring further exploration.


Assuntos
Imunodeficiência de Variável Comum/imunologia , Citocinas/imunologia , Imunoglobulinas/deficiência , Adulto , Células Cultivadas , Imunodeficiência de Variável Comum/sangue , Feminino , Expressão Gênica , Humanos , Imunoglobulinas/sangue , Leucócitos Mononucleares/imunologia , Receptores de Lipopolissacarídeos/sangue , Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade
16.
Gastroenterol Hepatol ; 45(1): 47-58, 2022 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34029644

RESUMO

INTRODUCTION: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. PATIENTS AND METHODS: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. RESULTS: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA. CONCLUSIONS: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.


Assuntos
Atresia Biliar/sangue , Atresia Biliar/diagnóstico , Complemento C3/análise , Área Sob a Curva , Atresia Biliar/complicações , Complemento C4/análise , Feminino , Humanos , Imunoglobulinas/sangue , Lactente , Icterícia Obstrutiva/etiologia , Subpopulações de Linfócitos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , gama-Glutamiltransferase/sangue
17.
Toxicology ; 465: 153047, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34838595

RESUMO

Recent evidences suggest the role of chronic lead (Pb) exposure in altering immunological parameters. Present study aimed to systematically review existing literature and synthesize quantitative evidence on the association between chronic Pb exposure and changes in immunological markers. Observational studies reporting immunological markers such as leukocyte derivative counts (CD3+, CD4+, CD8+, CD45+, CD56+, lymphocyte, and total leukocyte), cytokine, Immunoglobulin (Igs), C-reactive protein (CRP) among Pb-exposed and unexposed controls were systematically searched from PubMed, Scopus and Embase digital databases from inception to January 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered during systematic review. Mean differences in the immunological markers between Pb-exposed and control groups were pooled using random-effects model. The heterogeneity was assessed using Cochran-Q test and I2 statistic. The review included forty studies reporting immunological markers in Pb-exposed and unexposed control groups. The occupational Pb-exposed group exhibited significantly higher BLL, impaired immunological markers, characterized by a marginal lowering in lymphocyte count, lymphocyte subsets (CD3+, CD4+, CD4+/CD8+ ratio), IFN-γ and IgG levels, while CD8+, IgM, IgA, IgE, and cytokines (IL-4, IL-6, IL-10, and TNF-α) exhibited a trend of higher values in comparison to the control group. Further, inflammatory marker viz., total leukocyte count was significantly higher among Pb-exposed. The included studies exhibited high levels of heterogeneity. In conclusion, Occupational Pb exposure alters the immunological markers such as the circulating cytokines and leukocyte counts. However, high-quality, multicentered studies are required to strengthen present observations and further understand the Pb's role on the immune system. Prospero Registration ID: CRD42021228252.


Assuntos
Poluentes Ambientais/efeitos adversos , Sistema Imunitário/efeitos dos fármacos , Chumbo/efeitos adversos , Subpopulações de Linfócitos/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Antígenos CD/sangue , Biomarcadores/sangue , Citocinas/sangue , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunoglobulinas/sangue , Mediadores da Inflamação/sangue , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Medição de Risco
18.
Toxicology ; 465: 153057, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34864091

RESUMO

The large conjugated π bond in the molecular structure of carbon nanotubes (CNTs) interacts with the benzene ring structure in di (n-butyl) phthalates (DBP) through a π - π bond. Compounds of CNTs and DBP form easily, becoming another environmental pollutant of concern. We explore whether CNTs entering animals slow down the degradation of the DBP adsorbed in the CNT cavity, thereby prolonging the "hormonal activity" of DBP. In our study, male BALb/c mice were used as experimental subjects divided into four groups: the control group; the multi-walled carbon nanotubes (MWCNTs) exposure group (10mg/kg/d); the DBP exposure group (2.15 mg/kg/d); and the compound exposure group (MWCNTs + DBP). After 30 days of exposure, the mice were sacrificed and their spleens used for immunotoxicology study. The results showed that the exposure groups exhibited splenomegaly and suffered severe oxidative damage to the spleen. In the compound exposure group: levels of IgA and IgG in the serum of the mice changed, and were significantly different from levels in both the MWCNTs and DBP exposure groups (p <0.05); the pathological sections of the spleen showed that the boundary between the white pulp area (WP) and the red pulp area (RP) was blurred, that the cell arrangement was loose, and that more red blood cells were retained in the spleen. Proteomics mass spectrometry analysis showed that compared with the control group, 70 proteins were up-regulated and 27 proteins were down-regulated in the MWCNTs group, 36 proteins were up-regulated and 23 proteins were down-regulated in the DBP group, 87 proteins were up-regulated and 21 proteins were down-regulated in the compound exposure group. The results of GO enrichment analysis and KEGG enrichment analysis of the differentially expressed proteins showed that the compound exposure harmed the spleen antigen recognition, processing, and presentation, inhibited the activation and proliferation of B cells and T cells, and hindered the adaptive immune responses. Our results showed that MWCNTs and DBP compounds can damage the spleen, and impair the innate and adaptive immune functions of the body.


Assuntos
Dibutilftalato/toxicidade , Poluentes Ambientais/toxicidade , Nanotubos de Carbono/toxicidade , Baço/efeitos dos fármacos , Esplenomegalia/induzido quimicamente , Imunidade Adaptativa/efeitos dos fármacos , Animais , Redes Reguladoras de Genes , Imunidade Inata/efeitos dos fármacos , Imunoglobulinas/sangue , Masculino , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Proteoma/metabolismo , Medição de Risco , Baço/imunologia , Baço/metabolismo , Baço/patologia , Esplenomegalia/imunologia , Esplenomegalia/metabolismo , Esplenomegalia/patologia , Transcriptoma/efeitos dos fármacos
19.
Cell Mol Biol (Noisy-le-grand) ; 67(3): 11-23, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34933737

RESUMO

The use of plant extracts represents a promising approach for the synthesis of silver nanoparticles (AgNPs). This study reports the low-cost, green synthesis of AgNPs using the extract of clove and black seeds. The biosynthesized AgNPs were confirmed and characterized by analysis of the spectroscopy profile of the UV-visible spectrophotometer. The purpose of the present study is to evaluate the inhibitory effect concentration (MIC) of AgNPs, clove, and black cumin seed extracts on the growth and swarming of P. mirabilis. Clinical isolates of P. mirabilis were isolated from patients suffering from urinary tract infections. Thirteen types of antibiotics were used in the present study to detect their ability to inhibit P. mirabilis's resistance. Immunological findings included the determination of serum levels of IgG, IgM, IgA and complement protein C3 and C4. Results showed that IgG and IgA concentrations significantly increased (1311.13 ± 72.54 and 279 ± 21.31) respectively in UTI patients in comparison to the healthy control group which was 1089.88 ± 37.33 and 117.611 ± 4.19 respectively, While IgM concentrations were increased non significantly in UTI patients (153.331 ± 6.45) in comparison to healthy control (145.2 ± 13.49). Complement components C3 showed a significant increase in UTI patients with mean values of 125.95 ± 6.22 compared to the control group with mean values of 55.191 ± 9.64, while C4 showed statically non-significant among UTI patients in comparison with the control group (35.195 ± 2.34 and 34.371 ± 1.22) respectively.


Assuntos
Proteínas do Sistema Complemento/metabolismo , Imunoglobulinas/sangue , Nanopartículas Metálicas/administração & dosagem , Extratos Vegetais/farmacologia , Proteus mirabilis/efeitos dos fármacos , Prata/administração & dosagem , Infecções Urinárias/sangue , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Humanos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Nigella sativa/química , Extratos Vegetais/administração & dosagem , Proteus mirabilis/genética , Proteus mirabilis/fisiologia , Prata/química , Espectrofotometria/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Syzygium/química , Infecções Urinárias/metabolismo , Infecções Urinárias/microbiologia
20.
Anal Chem ; 93(46): 15236-15242, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34762405

RESUMO

In multiple myeloma (MM) disease, malignant plasma cells produce excessive quantities of a monoclonal immunoglobulin (Ig), known as M-protein. M-protein levels are measured in the serum of patients with MM using electrophoresis techniques to determine the response to treatment. However, therapeutic monoclonal antibodies, such as isatuximab, may confound signals using electrophoresis assays. We developed a robust assay based on immunocapture and liquid chromatography coupled to high-resolution mass spectrometry (IC-HPLC-HRMS) in order to eliminate this interference. Following immunocapture of Ig and free light chains (LC) in serum, heavy chains (HC) and LC were dissociated using dithiothreitol, sorted by liquid chromatography and analyzed using HRMS (Q-Orbitrap). This method allowed the M-proteins to be characterized and the signals from isatuximab and M-proteins to be discriminated. As M-protein is specific to each patient, no standards were available for absolute quantification. We therefore used alemtuzumab (an IgG kappa mAb) as a surrogate analyte for the semiquantification of M-protein in serum. This assay was successfully validated in terms of selectivity/specificity, accuracy/precision, robustness, dilution linearity, and matrix variability from 10.0 to 200 µg/mL in human serum. This method was used for clinical assessment of samples and eliminated potential interference due to isatuximab when monitoring patients with MM.


Assuntos
Anticorpos Monoclonais , Imunoglobulinas/sangue , Mieloma Múltiplo/diagnóstico , Anticorpos Monoclonais Humanizados , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Espectrometria de Massas
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