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1.
J Immunol Methods ; 499: 113166, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653504

RESUMO

Bluetongue virus (BTV), the causative agent of bluetongue disease infects many domestic and wild ruminants. In the present study, colloidal gold nanoparticle-based lateral flow immunochromatography assay (LFIA) was developed to detect the group-specific antibodies to BTV in serum samples of sheep, goats, cattle, and camel. The recombinant VP7 protein of BTV conjugated to colloidal gold nanoparticles (GNPs) was used as a detector reagent. Recombinant streptococcal protein G and monoclonal antibody to BTV group-specific antigen were immobilized as the test and the control line, respectively on a nitrocellulose membrane. The protein G could capture the specific antibodies to BTV present in the serum of multiple ruminant species susceptible to BTV in a common test format and could eliminate the requirement of multiple anti-species antibodies. Upon addition of serum sample, GNP-rVP7 protein-serum complex migrated laterally onto the strip via capillary action and results were analyzed based on appearance of red colour band at test and control line. Serum samples (n = 481) of sheep, goats, cattle, and camel segregated as positive and negative by the commercial competitive-ELISA (c-ELISA) kit were tested in the fabricated LFIA strips to analyze the performance of the assay. In comparison with c-ELISA, the relative diagnostic sensitivity (DSn) of 95.2% with 91.6-97.6 (95%)) confidence interval and relative diagnostic specificity (DSp) of 99.6% 97.8-100.0 (95%) confidence interval were obtained for the optimized LFIA. The agreement between the LFIA and the c-ELISA was excellent as indicated by the kappa coefficient value of 0.949 (SE = 0.0142) with 0.9219 to 0.9779 (95%) confidence interval. The recombinant protein G based LFIA is a sensitive, specific, rapid, one-step test that can be used in the field or poorly equipped laboratories for serological diagnosis and serosurveillance of bluetongue in multiple susceptible species.


Assuntos
Anticorpos/sangue , Imunoensaio , Proteínas do Core Viral/imunologia , Animais , Anticorpos/imunologia , Camelus , Bovinos , Cabras , Cobaias , Coelhos
2.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638989

RESUMO

The latest vaccination campaign has actualized the potential impact of antigenic stimuli on reproductive functions. To address this, we mimicked vaccination's effects by administering keyhole limpet hemocyanin (KLH ) to CD1 male mice and used their sperm for in vitro fertilization (IVF). Two-cell embryos after IVF with spermatozoa from control (C) or KLH-treated (Im) male mice were transferred to surrogate mothers mated with vasectomized control (C) or KLH-treated (Im) male mice, resulting in four experimental groups: C-C, Im-C, C-Im, and Im-Im. The pre-implantation losses were significantly lower in the Im-C group than in the C-Im group. At the same time, the resorption rates reduced markedly in the C-Im compared to the Im-C group. Embryo and placenta weights were significantly higher in the Im-Im group. Although the GM-CSF levels were lower in the amniotic fluid of the gestating surrogate mothers in the Im-Im group, they were strongly correlated with embryo mass. The number-size trade-off was only significant in the Im-Im group. This suggests a positive, cooperative effect of spermatozoa and seminal fluid from immune-primed males on embryo growth and the optimal distribution of surrogate mother maternal resources despite the negative impact of males' antigenic challenge on the IVF success rate.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Transferência Embrionária/métodos , Desenvolvimento Embrionário/imunologia , Fertilização In Vitro/métodos , Hemocianinas/administração & dosagem , Sêmen/imunologia , Espermatozoides/imunologia , Vacinação/métodos , Animais , Anticorpos/sangue , Blastocisto/imunologia , Blastocisto/metabolismo , Divisão Celular/imunologia , Implantação do Embrião/imunologia , Feminino , Hemocianinas/imunologia , Imunoglobulina G/sangue , Masculino , Camundongos , Gravidez , Vasectomia/métodos
3.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576131

RESUMO

The cyclical proliferation of the wild fossorial rodent Arvicola terrestris scherman (ATS) is critical in mid-mountain ecosystems of several European countries. Our goal is to develop an immunocontraceptive vaccine to control their fertility, as a sustainable alternative to chemical poisons currently used. Indeed, these chemicals cause the death of ATS predators and animals sharing their ecosystem, and current laws progressively limit their use, making the development of a targeted vaccination strategy an interesting and efficient alternative. In order to identify species-specific sperm antigens, male and female ATS received subcutaneous injections of whole ATS spermatozoa to elicit an immune response. The analysis of the immune sera led to the identification of 120 immunogenic proteins of sperm cells. Of these, 15 were strictly sperm-specific and located in different regions of the male gamete. Some of these antigens are proteins involved in molecular events essential to the reproductive process, such as sperm-egg interaction, acrosomal reaction, or sperm motility. This approach not only identified a panel of immunogenic proteins from ATS sperm cells, but also demonstrated that some of these proteins trigger an immune response in both male and female ATS. These spermatic antigens are good candidates for the development of a contraceptive vaccine.


Assuntos
Antígenos/metabolismo , Arvicolinae/imunologia , Anticoncepcionais , Espermatozoides/imunologia , Animais , Anticorpos/sangue , Feminino , Ontologia Genética , Imunidade , Imunização , Masculino , Proteínas de Membrana/metabolismo , Peptídeos/metabolismo , Proteômica , Especificidade da Espécie
4.
Clin Appl Thromb Hemost ; 27: 10760296211040110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34541935

RESUMO

Since the outbreak of Covid-19 in December, 2019, scientists worldwide have been committed to developing COVID-19 vaccines. Only when most people have immunity to SARS-CoV-2, COVID-19 can reduce even wholly overcome. So far, nine kinds of COVID-19 vaccines have passed the phase III clinical trials and have approved for use. At the same time, adverse reactions after COVID-19 vaccination have also reported. This paper focuses on the adverse effects of thrombosis and thrombocytopenia caused by the COVID-19 vaccine, especially the adenovirus-vector vaccine from AstraZeneca and Pfizer, and discusses its mechanism and possible countermeasures.


Assuntos
Adenoviridae/genética , Vacinas contra COVID-19/efeitos adversos , Vetores Genéticos , Trombocitopenia/induzido quimicamente , Trombose/induzido quimicamente , Vacinação/efeitos adversos , Anticorpos/sangue , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Humanos , Fator Plaquetário 4/imunologia , Medição de Risco , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/imunologia , Trombose/sangue , Trombose/imunologia
5.
Front Immunol ; 12: 677190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335576

RESUMO

Background: Neuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory diseases mediated mainly by humoral and cellular immunity. Circulating follicular helper T (Tfh) cells are thought to be involved in the pathogenesis of NMOSD, and serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of Tfh cells on B-cell-mediated humoral immunity. Immune cell and cytokine changes during the dynamic relapsing and remitting processes in NMOSD require further exploration. Patients and methods: Blood samples were collected from 36 patients in acute and recovery phases of NMOSD, 20 patients with other noninflammatory neurological diseases (ONND) and 20 age- and sex-matched healthy volunteers. CD4+CXCR5+PD-1+ Tfh cells were detected by flow cytometry, and serum CXCL13 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results: The percentage of CD4+CXCR5+PD-1+ Tfh cells was significantly higher during the acute phase than during the recovery phase, and serum CXCL13 levels were significantly higher in patients in the acute and recovery phases of NMOSD than in the ONND and control groups. The Tfh cell percentage was positively correlated with CXCL13 levels, and both were positively correlated with Expanded Disability Status Scale (EDSS) scores and cerebrospinal fluid protein levels in patients with acute NMOSD. Conclusion: Circulating Tfh cells level has the potential to be a biomarker of disease severity.


Assuntos
Quimiocina CXCL13/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/imunologia , Índice de Gravidade de Doença , Células T Auxiliares Foliculares/imunologia , Adulto , Anticorpos/sangue , Anticorpos/imunologia , Aquaporina 4/imunologia , Biomarcadores/sangue , Antígenos CD4/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Celular , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Receptores CXCR5/metabolismo
7.
Molecules ; 26(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34443589

RESUMO

The thrombotic thrombocytopenia syndrome (TTS), a complication of COVID-19 vaccines, involves thrombosis (often cerebral venous sinus thrombosis) and thrombocytopenia with occasional pulmonary embolism and arterial ischemia. TTS appears to mostly affect females aged between 20 and 50 years old, with no predisposing risk factors conclusively identified so far. Cases are characterized by thrombocytopenia, higher levels of D-dimers than commonly observed in venous thromboembolic events, inexplicably low fibrinogen levels and worsening thrombosis. Hyper fibrinolysis associated with bleeding can also occur. Antibodies that bind platelet factor 4, similar to those associated with heparin-induced thrombocytopenia, have also been identified but in the absence of patient exposure to heparin treatment. A number of countries have now suspended the use of adenovirus-vectored vaccines for younger individuals. The prevailing opinion of most experts is that the risk of developing COVID-19 disease, including thrombosis, far exceeds the extremely low risk of TTS associated with highly efficacious vaccines. Mass vaccination should continue but with caution. Vaccines that are more likely to cause TTS (e.g., Vaxzevria manufactured by AstraZeneca) should be avoided in younger patients for whom an alternative vaccine is available.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/terapia , Trombose/induzido quimicamente , Trombose/terapia , Anticorpos/sangue , Diagnóstico Diferencial , Heparina/efeitos adversos , Humanos , Fator Plaquetário 4/sangue , Trombocitopenia/etiologia , Trombose/etiologia
8.
Transfusion ; 61 Suppl 1: S214-S222, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269431

RESUMO

BACKGROUND: Reliability of ABO-antibody measurement is important in the context of supplying low-titer ABO incompatible plasma-containing blood products. This study investigated the correlation of anti-A measurements between three different titer methodologies. METHODS: Thirty-four blood group O individuals were included. IgM and IgG anti-A was measured by three different methods: (1) manual method (Bio-Rad ID-gel card), (2) automated method (Immucor NEO), (3) flow cytometry (FC) with calibration in molecules of equivalent fluorochrome (MEF). Data were log2 transformed to titer steps (TS) and log2 MEF, respectively. All three methods were benchmarked against the 14/300 WHO anti-A/anti-B standard reagent. RESULTS: The correlation between the manual and automated methods was statistically significant for both IgM (Spearman's rs  = 0.89, p < .0001) and IgG (rs  = 0.95, p < .0001). The mean TS difference between the manual and automated methods was 0.61 for IgM (p = .0033) and 2.1 for IgG (p < .0001). The manual method yielded IgM titer results that were generally 1 titer step higher than the automated method, whereas for the IgG titrations the difference was generally a median of 2 TS higher. The FC median log2 MEF level was significantly correlated with TS of IgG and IgM for both manual and automated agglutination-based titer methods (0.69 ≤ r2  ≤ 0.91). With the WHO standard reagent, the manual method produced the expected results while the automated method's results were 1 TS lower for both IgM and IgG at all dilutions tested. CONCLUSION: These results indicate that all three methods are suitable for measuring anti-A in group O whole blood.


Assuntos
Anticorpos/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Anticorpos/sangue , Citometria de Fluxo , Humanos , Testes Imunológicos , Reprodutibilidade dos Testes
9.
J Am Soc Nephrol ; 32(8): 2070-2082, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34301794

RESUMO

BACKGROUND: Circulating anti-HLA donor-specific antibodies (HLA-DSA) are often absent in kidney transplant recipients with microvascular inflammation (MVI). Missing self, the inability of donor endothelial cells to provide HLA I-mediated signals to inhibitory killer cell Ig-like receptors (KIRs) on recipient natural killer cells, can cause endothelial damage in vitro, and has been associated with HLA-DSA-negative MVI. However, missing self's clinical importance as a nonhumoral trigger of allograft rejection remains unclear. METHODS: In a population-based study of 924 consecutive kidney transplantations between March 2004 and February 2013, we performed high-resolution donor and recipient HLA typing and recipient KIR genotyping. Missing self was defined as the absence of A3/A11, Bw4, C1, or C2 donor genotype, with the presence of the corresponding educated recipient inhibitory KIR gene. RESULTS: We identified missing self in 399 of 924 transplantations. Co-occurrence of missing self types had an additive effect in increasing MVI risk, with a threshold at two concurrent types (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.26 to 2.53), independent of HLA-DSA (HR, 5.65; 95% CI, 4.01 to 7.96). Missing self and lesions of cellular rejection were not associated. No HLA-DSAs were detectable in 146 of 222 recipients with MVI; 28 of the 146 had at least two missing self types. Missing self associated with transplant glomerulopathy after MVI (HR, 2.51; 95% CI, 1.12 to 5.62), although allograft survival was better than with HLA-DSA-associated MVI. CONCLUSION: Missing self specifically and cumulatively increases MVI risk after kidney transplantation, independent of HLA-DSA. Systematic evaluation of missing self improves understanding of HLA-DSA-negative MVI and might be relevant for improved diagnostic classification and patient risk stratification.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Células Matadoras Naturais/imunologia , Receptores KIR/genética , Vasculite/genética , Adulto , Idoso , Anticorpos/sangue , Feminino , Genótipo , Sobrevivência de Enxerto , Antígeno HLA-A11/genética , Antígeno HLA-A11/imunologia , Antígeno HLA-A3/genética , Antígeno HLA-A3/imunologia , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Teste de Histocompatibilidade , Humanos , Transplante de Rim , Masculino , Microvasos , Pessoa de Meia-Idade , Receptores KIR2DL2/genética , Receptores KIR2DL3/genética , Doadores de Tecidos , Transplantados , Vasculite/complicações
10.
Sci Rep ; 11(1): 14976, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294782

RESUMO

Measurements of serum concentrations of therapeutic antibodies and anti-drug antibodies (ADA) can support clinical decisions for the management of non-responders, optimizing the therapy. In the present study we compared the results obtained by classical ELISA and a recently proposed surface plasmon resonance (SPR)-based immunoassay, in 76 patients receiving infliximab for inflammatory bowel diseases. The two methods indicated very similar serum concentrations of the drug, but there were striking differences as regards ADA. All the sera showing ADA by ELISA (14) also showed ADA by SPR, but the absolute amounts were different, being 7-490 times higher with SPR, with no correlation. Eight patients showed ADA only with SPR, and these ADA had significantly faster dissociation rate constants than those detectable by both SPR and ELISA. The underestimation, or the lack of detection, of ADA by ELISA is likely to reflect the long incubation steps which favor dissociation of the patient's low-affinity ADA, while the commercial, high-affinity anti-infliximab antibodies used for the calibration curve do not dissociate. This problem is less important with SPR, which monitors binding in real time. The possibility offered by SPR to detect ADA in patients otherwise considered ADA-negative by ELISA could have important implications for clinicians.


Assuntos
Anticorpos/sangue , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Tomada de Decisão Clínica , Ensaio de Imunoadsorção Enzimática , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Infliximab/imunologia , Limite de Detecção , Quimioterapia de Manutenção , Ressonância de Plasmônio de Superfície , Resultado do Tratamento
11.
Front Immunol ; 12: 681328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305913

RESUMO

Inducing antigen-specific tolerance is a promising treatment for preventing or reversing Type 1 diabetes (T1D). In contrast to a vaccine that induces immune responses against pathogens, a tolerogenic vaccine can suppress immunity against antigens causing diseases by administrating a mixture of self-antigens with an adjuvant that decreases the strength of antigen-specific response. Kynurenine (Kyn) is an endogenous substance that can inhibit the natural killer cell and T cell proliferation and promote the differentiation of naïve T cells into regulatory T cells (Tregs). In this study, we evaluated the efficacy of Kyn as a novel suppressive adjuvant. Kyn was co-immunized with GAD65 phage vaccine to induce Treg cells and tolerogenic responses for the prevention of T1D in NOD mouse model. Mice were subcutaneously immunized two times with 1011 Pfu (100µL,1012 Pfu/ml) GAD65 phage vaccine doses mixed with 200 µg of Kyn. Serum antibodies and cytokines were detected by ELISA and electrochemiluminescence, respectively. Flow cytometry assay was used to analyze DC and Treg. MTS was used for the analysis of spleen lymphocyte proliferation. RNA sequencing was used to investigate mRNA and miRNA expression profiles in spleen lymphocytes. Compared to GAD65 phage vaccine alone, co-immunization of Kyn and GAD65 phage vaccine resulted in the prevention of hyperglycemia in 60% of mice for at least one month. Further, Kyn enhances GAD65-specific Th2-mediated immune responses; regulates the Th1/Th2 imbalance and increases the secretion of Th2 cytokines and the number of CD4+CD25+Foxp3+T cells; suppresses DC maturation and GAD65-specific T lymphocyte proliferation. Moreover, we integrated Kyn related miRNA and mRNA expression profiles obtained from the spleen lymphocyte RNA-sequencing which was stimulated by Kyn in vitro. These data provide an important basis for understanding the mechanisms underlying Kyn as an immunosuppressive adjuvant which regulated the immune response. These findings suggest that Kyn can serve as an effective suppressive adjuvant candidate for Type 1 diabetes vaccines.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Cinurenina/administração & dosagem , Vacinas/imunologia , Animais , Anticorpos/sangue , Anticorpos/imunologia , Biologia Computacional/métodos , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Imunização , Imunomodulação , Ativação Linfocitária , Contagem de Linfócitos , Camundongos , Vacinas/administração & dosagem
12.
J Immunol Methods ; 497: 113108, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34329690

RESUMO

Cardiovascular disease has remained the world's biggest killer for 30 years. To aid in the diagnosis and prognosis of patients suffering cardiovascular-related disease accurate detection methods are essential. For over 20 years, the cardiac-specific troponins, I (cTnI) and T (cTnT), have acted as sensitive and specific biomarkers to assist in the diagnosis of various types of heart diseases. Various cardiovascular complications were commonly detected in patients with COVID-19, where cTn elevation is detectable, which suggested potential prognostic value of cTn in COVID-19-infected patients. Detection of these biomarkers circulating in the bloodstream is generally facilitated by immunoassays employing cTnI- and/or cTnT-specific antibodies. While several anti-troponin assays are commercially available, there are still obstacles to overcome to achieve optimal troponin detection. Such obstacles include the proteolytic degradation of N and C terminals on cTnI, epitope occlusion of troponin binding-sites by the cTnI/cTnT complex, cross reactivity of antibodies with skeletal troponins or assay interference caused by human anti-species antibodies. Therefore, further research into multi-antibody based platforms, multi-epitope targeting and rigorous validation of immunoassays is required to ensure accurate measurements. Moreover, in combination with various technical advances (e.g. microfluidics), antibody-based troponin detection systems can be more sensitive and rapid for incorporation into portable biosensor systems to be used at point-of care.


Assuntos
Anticorpos/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Imunoensaio/métodos , Troponina I/sangue , Troponina T/sangue , Anticorpos/imunologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Humanos , Prognóstico , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Troponina I/imunologia , Troponina T/imunologia
13.
Sci Rep ; 11(1): 14603, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272440

RESUMO

To evaluate the clinical characteristics of optic neuritis (ON) with different phenotypes. This prospective study recruited patients with new-onset ON between January 2015 and March 2017 who were followed-up for 3 years. They were divided into the myelin oligodendrocyte glycoprotein-seropositive (MOG-ON), aquaporin-4-seropositive (AQP4-ON), and double-seronegative (seronegative-ON) groups, and their clinical characteristics and imaging findings were evaluated and compared. Two-hundred-eighty patients (405 eyes) were included (MOG-ON: n = 57, 20.4%; AQP4-ON: n = 98, 35.0%; seronegative-ON: n = 125, 44.6%). The proportion of eyes with best-corrected visual acuity > 20/25 at the 3-year follow-up was similar between the MOG-ON and seronegative-ON groups; the proportion in both groups was higher than that in the AQP4-ON group (p < 0.001). Relapse rates were higher in the MOG-ON and AQP4-ON groups than in the seronegative-ON group (p < 0.001). Average retinal nerve fiber layer (RNFL) thickness at 3 years was similar between the MOG-ON and AQP4-ON groups (63.41 ± 13.39 and 59.40 ± 11.46 µm, p = 0.476) but both were thinner than the seronegative-ON group (74.06 ± 11.14 µm, p < 0.001). Macular ganglion cell-inner plexiform layer (GCIPL) revealed the same pattern. Despite RNFL and GCIPL thinning, the MOG-ON group's outcome was as favorable as that of the seronegative-ON group, whereas the AQP4-ON group showed unsatisfactory results.


Assuntos
Anticorpos/sangue , Aquaporina 4/imunologia , Biomarcadores/sangue , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/patologia , Adolescente , Adulto , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neurite Óptica/epidemiologia , Fenótipo , Estudos Prospectivos , Recidiva , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto Jovem
14.
Front Immunol ; 12: 671185, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194432

RESUMO

Introduction: ABO blood group antigens within grafts are continuously exposed to anti-A/B antibodies in the serum of recipients after ABO-incompatible (ABOi) kidney transplantation and are instrumental in antibody-mediated rejection. Some individuals secrete soluble blood group antigens into body fluids. In this study, we investigated the effect of donor and recipient secretor status on the outcomes of ABOi kidney transplantation. Methods: Data of a total of 32 patients with ABOi living donor kidney transplantation were retrospectively collected between 2014 and 2020 in West China Hospital. The genotype and phenotype of both donors and recipients were examined and evaluated with post-transplantation anti-A/B titer changes, graft function, and rejection. Results: Of the 32 recipients and 32 donors, 23 (71.9%) recipients and 27 (84.4%) donors had secretor genotypes, whereas 9 (28.1%) recipients and 5 (15.6%) donors did not. Anti-A/B titers after ABOi kidney transplantation were not significantly influenced by the secretor status of either donors or recipients. The post-transplantation serum creatinine (Scr) levels and estimated glomerular filtration rate (eGFR) was better in weak- or non-secretor recipients at day 30 (Scr P = 0.047, eGFR P = 0.008), day 90 (Scr P = 0.010, eGFR P = 0.005), and month 9 (eGFR P = 0.008), and recipients from secretor donors had a lower incidence of graft rejection in the first year after ABOi transplantation (P = 0.004). Conclusions: A weak secretor status phenotype was found in both genotypes, i.e., individuals who secreted soluble antigens as well as those who did not. The recipient ABH-secretor status may have an influence on early posttransplant renal function, and the donor ABH-secretor status might affect the incidence of graft rejection.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Genótipo , Rejeição de Enxerto/imunologia , Transplante de Rim , Rim/metabolismo , Anticorpos/sangue , Tipagem e Reações Cruzadas Sanguíneas , Creatinina/sangue , Taxa de Filtração Glomerular , Rejeição de Enxerto/mortalidade , Humanos , Rim/patologia , Doadores Vivos , Fenótipo , Estudos Retrospectivos , Análise de Sobrevida
15.
JAMA ; 326(4): 332-338, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34213527

RESUMO

Importance: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. Objective: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. Design, Setting, and Participants: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. Exposures: Diagnosis of cerebral venous sinus thrombosis. Main Outcomes and Measures: Frequencies of admission thrombocytopenia (platelet count <150 ×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples). Results: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/µL) in 52 (6.0%), moderate (50-99 ×103/µL) in 17 (2.0%), and severe (<50 ×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Heparina/imunologia , Fator Plaquetário 4/imunologia , Trombose dos Seios Intracranianos/complicações , Trombocitopenia/etiologia , Adulto , Anticorpos/sangue , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose dos Seios Intracranianos/imunologia , Trombocitopenia/epidemiologia
16.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203838

RESUMO

The phosphatidylinositol 3-kinase (PI3K) family of enzymes plays a determinant role in inflammation and autoimmune responses. However, the implication of the different isoforms of catalytic subunits in these processes is not clear. Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that entails innate and adaptive immune response elements in which PI3K is a potential hub for immune modulation. In a mouse transgenic model with T-cell-specific deletion of p110α catalytic chain (p110α-/-ΔT), we show the modulation of collagen-induced arthritis (CIA) by this isoform of PI3K. In established arthritis, p110α-/-ΔT mice show decreased prevalence of illness than their control siblings, higher IgG1 titers and lower levels of IL-6 in serum, together with decreased ex vivo Collagen II (CII)-induced proliferation, IL-17A secretion and proportion of naive T cells in the lymph nodes. In a pre-arthritis phase, at 13 days post-Ag, T-cell-specific deletion of p110α chain induced an increased, less pathogenic IgG1/IgG2a antibodies ratio; changes in the fraction of naive and effector CD4+ subpopulations; and an increased number of CXCR5+ T cells in the draining lymph nodes of the p110α-/-ΔT mice. Strikingly, T-cell blasts in vitro obtained from non-immunized p110α-/-ΔT mice showed an increased expression of CXCR5, CD44 and ICOS surface markers and defective ICOS-induced signaling towards Akt phosphorylation. These results, plus the accumulation of cells in the lymph nodes in the early phase of the process, could explain the diminished illness incidence and prevalence in the p110α-/-ΔT mice and suggests a modulation of CIA by the p110α catalytic chain of PI3K, opening new avenues of intervention in T-cell-directed therapies to autoimmune diseases.


Assuntos
Artrite Experimental/enzimologia , Artrite Experimental/patologia , Domínio Catalítico , Classe Ia de Fosfatidilinositol 3-Quinase/química , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Linfócitos T/enzimologia , Animais , Anticorpos/sangue , Artrite Experimental/sangue , Artrite Experimental/imunologia , Biomarcadores/metabolismo , Proliferação de Células , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Modelos Animais de Doenças , Deleção de Genes , Imunidade , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Interleucina-6/sangue , Linfonodos/patologia , Camundongos Endogâmicos C57BL , Transdução de Sinais
17.
Sci Rep ; 11(1): 11632, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079038

RESUMO

Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03-2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69-0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient's age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.


Assuntos
Anticorpos/sangue , Antirreumáticos/imunologia , Artrite Reumatoide/imunologia , Fator Ativador de Células B/imunologia , Inibidores do Fator de Necrose Tumoral/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adalimumab/imunologia , Adalimumab/uso terapêutico , Idoso , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/antagonistas & inibidores , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Fator Ativador de Células B/antagonistas & inibidores , Fator Ativador de Células B/genética , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Certolizumab Pegol/imunologia , Certolizumab Pegol/uso terapêutico , Estudos de Coortes , Expressão Gênica , Humanos , Infliximab/imunologia , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética
18.
PLoS Negl Trop Dis ; 15(6): e0009378, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34081700

RESUMO

BACKGROUND: Sand fly saliva exposure plays an important role in immunity against leishmaniasis where it has mostly been associated with protection. Phlebotomus (Ph.) alexandri transmits Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), in Iraq. Our group recently demonstrated that 20% of Operation Iraqi Freedom (OIF) deployers had asymptomatic VL (AVL) indicative of prior infection by the parasite L. infantum. Little is known about Ph. alexandri saliva, and the human immune response to it has never been investigated. Here, we characterize the humoral and cellular immune response to vector saliva in OIF deployers naturally exposed to bites of Ph. alexandri and characterize their immunological profiles in association to AVL. METHODOLOGY/PRINCIPAL FINDINGS: The humoral response to Ph. alexandri salivary gland homogenate (SGH) showed that 64% of 200 OIF deployers developed an antibody response. To assess the cellular immune response to saliva, we selected a subcohort of subjects based on their post-travel (median 4 months; range 1-22 months) antibody response (SGH Antibody [Ab] positive or negative) as well as their AVL status; ten never-traveled controls were also included. Banked peripheral blood mononuclear cells (PBMC), collected ~10 years after end of deployment, were stimulated with SGH for 96 hours. The levels of IFN- γ, IL-6, IL-10, IL-13 and IL-17 were determined by ELISA. Our findings indicate that OIF deployers mounted a cellular response to SGH where the anti-SGH+ asymptomatic subjects developed the highest cytokine levels. Further, stimulation with SGH produced a mixture of pro-inflammatory and anti-inflammatory cytokines. Contrary to our hypothesis, we observed no correlation between the cellular immune response to Ph. alexandri SGH and prevention from asymptomatic infection with L. infantum. CONCLUSIONS/SIGNIFICANCE: As we found, although all infected deployers demonstrated persistent disease control years after deployment, this did not correlate with anti-saliva systemic cellular response. More exposure to this vector may facilitate transmission of the L. infantum parasite. Since exposure to saliva of Ph. alexandri may alter the human immune response to bites of this vector, this parameter should be taken into consideration when considering the VL risk.


Assuntos
Insetos Vetores/imunologia , Leishmaniose Visceral/transmissão , Phlebotomus/imunologia , Saliva/imunologia , Adulto , Animais , Anticorpos/sangue , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Iraque/epidemiologia , Leishmania infantum/imunologia , Leishmaniose Visceral/epidemiologia , Leucócitos Mononucleares , Masculino , Risco , Células Th2
19.
BMC Med ; 19(1): 131, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34103026

RESUMO

BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.


Assuntos
Anticorpos , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Anticorpos/sangue , Isquemia Encefálica/diagnóstico , Estudos de Casos e Controles , Fator de Especificidade de Clivagem e Poliadenilação/imunologia , Proteínas de Ligação a DNA/imunologia , Fatores de Transcrição Forkhead/imunologia , Humanos , Acidente Vascular Cerebral/diagnóstico
20.
Parasit Vectors ; 14(1): 309, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099029

RESUMO

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life-threatening diseases in humans and animals. Paramyosin (Pmy) is not only an invertebrate-specific myofibrillar protein but also an important immunomodulatory protein. Therefore, it is one of the ideal candidate antigens for vaccines. METHODS: We conducted two vaccine trials to evaluate the protective efficacy of Pmy recombinant protein (rPmy) and peptide vaccine (KLH-LEE). Each rabbit was immunized with three doses of rPmy or KLH-LEE adjuvanted with Freund's complete/incomplete at 500 µg/dose at 2-week intervals before challenge with 40 female H. longicornis/rabbit. PBS plus adjuvant, Trx or KLH was used as control group. The antibodies of rabbits were detected by ELISA. Then, female ticks were fed on the rabbits until detachment. RESULTS: ELISA results showed that both vaccines induced rabbits to produce antibodies. Compared with the Trx group, the engorgement weight, oviposition and hatchability of the rPmy group decreased by 8.87%, 26.83% and 38.86%, respectively. On the other hand, engorgement weight, oviposition and hatchability of female ticks in the KLH-LEE group correspondingly resulted in 27.03%, 53.15% and 38.40% reduction compared with that of the KLH group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 60.37% efficacy of the rPmy vaccine formulation and 70.86% efficacy in the KLH-LEE group. CONCLUSIONS: Pmy and particularly epitope LEE have potential for further development of an effective candidate vaccine to protect the host against tick infection. GRAPHIC ABSTARCT.


Assuntos
Proteínas de Artrópodes/administração & dosagem , Ixodidae/imunologia , Coelhos/imunologia , Infestações por Carrapato/veterinária , Tropomiosina/administração & dosagem , Vacinas/administração & dosagem , Animais , Anticorpos/sangue , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Imunização , Ixodidae/genética , Coelhos/sangue , Coelhos/parasitologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Infestações por Carrapato/sangue , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle , Tropomiosina/genética , Tropomiosina/imunologia , Vacinas/genética , Vacinas/imunologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia
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