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1.
Pediatr Transplant ; 26(8): e14400, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36168673

RESUMO

BACKGROUND: The role of angiotensin II type 1 receptor antibodies (AT1R-Ab) in pediatric renal transplantation is unclear. Here, we evaluated pre-transplant AT1R-Ab on transplant outcomes in the first 5 years. Secondary analysis compared pre-transplant AT1R-Ab levels by age. METHODS: Thirty-six patients, 2-20 years old, were divided into two groups: pre-transplant AT1R-Ab- (<17 U/ml; n = 18) and pre-transplant AT1R-Ab+ (≥17 U/ml; n = 18). eGFR was determined at 6-month, 1-, 2-, and 4-year post-transplant. Allograft biopsies were performed in the setting of strong HLA-DSA (MFI > 10 000), AT1R-Ab ≥17 U/ml, and/or elevated creatinine. RESULTS: Mean age in pre-transplant AT1R-Ab- was 13.3 years vs. 11.0 in pre-transplant AT1R-Ab+ (p = 0.16). At 6 months, mean eGFR was 111.3 ml/min/1.73 m2 in pre-transplant AT1R-Ab- vs. 100.2 in pre-transplant AT1R-Ab + at 1 year, 103.6 ml/min/1.73 m2 vs. 100.5; at 2 years, 98.9 ml/min/1.73 m2 vs. and 93.7; at 4 years, 72.6 ml/min/1.73 m2 vs. 80.9. 11/36 patients had acute rejection (6 in pre-transplant AT1R-Ab-, 5 in pre-transplant AT1R-Ab + ). There was no difference in rejection rates. All 6 subjects with de novo HLA-DSA and AT1R-Ab ≥17 U/ml at the time of biopsy experienced rejection. Mean age in those with the AT1R-Ab ≥40 U/ml was 10.0 years vs. 13.2 in those <40 U/ml (p = 0.07). CONCLUSION: In our small cohort, pre-transplant AT1R-Ab ≥17 U/ml was not associated with reduced graft function or rejection. The pathogenicity of pre-transplant AT1R-Ab in pediatric kidney transplantation requires further investigation.


Assuntos
Anticorpos , Rejeição de Enxerto , Transplante de Rim , Receptor Tipo 1 de Angiotensina , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Adulto Jovem , Anticorpos/sangue , Estudos de Coortes , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Rim/patologia , Receptor Tipo 1 de Angiotensina/imunologia
2.
Viruses ; 14(8)2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-36016268

RESUMO

Yellow Fever disease is caused by the Yellow Fever virus (YFV), an arbovirus from the Flaviviridae family. The re-emergence of Yellow Fever (YF) was facilitated by the increasing urbanization of sylvatic areas, the wide distribution of the mosquito vector, and the low percentage of people immunized in the Americas, which caused severe outbreaks in recent years, with a high mortality rate. Therefore, serological approaches capable of discerning antibodies generated from the wild-type (YFV-WT) strain between the vaccinal strain (YFV-17DD) could facilitate vaccine coverage surveillance, enabling the development of strategies to avoid new outbreaks. In this study, peptides were designed and subjected to microarray procedures with sera collected from individuals infected by WT-YFV and 17DD-YFV of YFV during the Brazilian outbreak of YFV in 2017/2018. From 222 screened peptides, around ten could potentially integrate serological approaches aiming to differentiate vaccinated individuals from naturally infected individuals. Among those peptides, one was synthesized and validated through ELISA.


Assuntos
Peptídeos , Vacina contra Febre Amarela , Febre Amarela , Anticorpos/sangue , Humanos , Peptídeos/sangue , Peptídeos/imunologia , Febre Amarela/sangue , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle , Vacina contra Febre Amarela/imunologia
3.
Asia Pac J Clin Nutr ; 31(2): 229-241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35766559

RESUMO

BACKGROUND AND OBJECTIVES: Adverse environmental factors in tunnels increase the occurrence of respiratory and intestinal inflammatory disease, which is seriously harmful to worker health. It is reported that medium-chain triglycerides (MCT) can improve immune status and alter the gut microflora. This study investigates MCT effects on immune status and gut microbiota among tunnel workers. METHODS AND STUDY DESIGN: Forty-five workers were randomly divided into an MCT group (n=30) and control group (n=15), where they ingested MCT-milk or a placebo milk for 12 weeks, respectively. The primary outcome measure was the incidence of respiratory infection and diarrhea. Secondary outcomes were changes in serum immune-related markers and changes in gut microbiota. RESULTS: The incidence of diarrhea in MCT group was significantly decreased after 4 weeks (p<0.01), with no significant differences in the control group. MCT reduced the level of pro-inflammatory cytokines (TNF-α, CRP, and IL-6) and enhanced the anti-inflammatory cytokines (IL-10, C3, C4, IgA, IgG, and IgM), respectively (p<0.01). The Chao index was reduced (p<0.01) and microbiota composition changed significantly after 12 weeks of MCT intervention. MCT reduced the abundance of Bacteroides, Roseburia, Ruminococcus_1, Lachnospira and increased that of Blautia and Fusicatenibacter at the genus level (p<0.01). CONCLUSIONS: The consumption of MCT reduces diarrhea occurrence and improves serum immune profiles together with gut microbiomics in tunnel workers.


Assuntos
Diarreia , Microbioma Gastrointestinal , Enteropatias , Triglicerídeos , Anticorpos/sangue , China , Citocinas/sangue , Diarreia/terapia , Humanos , Inflamação/terapia , Enteropatias/terapia , Doenças Profissionais/terapia , Triglicerídeos/administração & dosagem
4.
PLoS One ; 17(2): e0263468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35108321

RESUMO

BACKGROUND: Mass vaccination is the key element in controlling current COVID-19 pandemic. Studies comparing immunogenicity of different COVID-19 vaccines are largely lacking. We aimed at measuring anti-S antibody (Ab) levels in individuals fully vaccinated with BNT162b2, BBIBP-CorV and Gam-COVID-Vac, as well as in COVID-19 convalescents. METHODS: In this cross-sectional study, serum was collected from 400 age- and sex-matched participants, 100 fully vaccinated with BNT162b2, 100 with BBIBP-CorV and 100 with Gam-COVID-Vac on the 28th day after the second vaccine dose, and 100 recovered from COVID-19 at least 28 days after symptom(s) resolution. Sera were analyzed using the LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy). Wilcoxon rank-sum or Kruskal-Wallis tests was used for comparison of Ab levels. RESULTS: Highest mean value (210.11, SD = 100.42) was measured in the BNT162b2 group, followed by Gam-COVID-Vac (171.11, SD = 120.69) and BBIBP-CorV (68.50, SD = 72.78) AU/mL (p<0.001). Significant differences in antibody levels were found between BNT162b2 and BBIBP-CorV (p<0.001), BNT162b2 and Gam-COVID-Vac (p = 0.001), as well as BBIBP-CorV and Gam-COVID-Vac groups (p<0.001). Percentage of seropositive was 81% in the convalescent group, 83% in BBIBP-CorV vaccinated and 100% in BNT162b2 and Gam-COVID-Vac. When comparing measured antibody levels in vaccinated to those in COVID-19 recovered, significantly higher antibody levels were found for vaccinated with BNT162b2 (p<0.001), and with Gam-COVID-Vac (p<0.001), while for BBIBP-CorV there was no statistically significant difference (p = 0.641). CONCLUSIONS: All three investigated vaccines, BNT162b2, BBIBP-CorV and Gam-COVID-Vac, provide robust immune response 28 days after the second dose of vaccine, in the majority of participants. All individuals vaccinated with BNT162b2 and Gam-COVID-Vac seroconverted, while in vaccinated with BBIBP-CorV and COVID-19 recovered seroconversion rates were lower. Although less potent compared to other two vaccines, immune response after BBIBP-CorV was similar to response measured in convalescents. Challenge still remains to examine dynamics and durability of immunoprotection.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/imunologia , COVID-19/terapia , Resultado do Tratamento , Adulto , Anticorpos/análise , Anticorpos/sangue , Anticorpos Antivirais/sangue , Vacina BNT162/imunologia , COVID-19/sangue , Vacinas contra COVID-19/imunologia , Convalescença , Estudos Transversais , Feminino , Humanos , Imunidade/imunologia , Imunidade Inata/imunologia , Imunogenicidade da Vacina/imunologia , Imunoglobulina G/análise , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Sérvia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologia
5.
Parasit Vectors ; 15(1): 4, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983601

RESUMO

Human and animal pathogens that are transmitted by arthropods are a global concern, particularly those vectored by ticks (e.g. Borrelia burgdorferi and tick-borne encephalitis virus) and mosquitoes (e.g. malaria and dengue virus). Breaking the circulation of pathogens in permanent foci by controlling vectors using acaricide-based approaches is threatened by the selection of acaricide resistance in vector populations, poor management practices and relaxing of control measures. Alternative strategies that can reduce vector populations and/or vector-mediated transmission are encouraged worldwide. In recent years, it has become clear that arthropod-associated microbiota are involved in many aspects of host physiology and vector competence, prompting research into vector microbiota manipulation. Here, we review how increased knowledge of microbial ecology and vector-host interactions is driving the emergence of new concepts and tools for vector and pathogen control. We focus on the immune functions of host antibodies taken in the blood meal as they can target pathogens and microbiota bacteria within hematophagous arthropods. Anti-microbiota vaccines are presented as a tool to manipulate the vector microbiota and interfere with the development of pathogens within their vectors. Since the importance of some bacterial taxa for colonization of vector-borne pathogens is well known, the disruption of the vector microbiota by host antibodies opens the possibility to develop novel transmission-blocking vaccines.


Assuntos
Anticorpos/imunologia , Vetores Artrópodes/imunologia , Transmissão de Doença Infecciosa/prevenção & controle , Desenvolvimento de Vacinas/métodos , Animais , Anticorpos/sangue , Hemolinfa/imunologia , Interações Hospedeiro-Patógeno , Humanos , Glândulas Salivares/imunologia
6.
Toxicol Lett ; 359: 22-30, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35092809

RESUMO

Polyethylene glycol (PEG) is present in a variety of products. Little is known regarding the accumulation of high-molecular-weight PEGs or the long-term effects resulting from PEG accumulation in certain tissues, especially the choroid plexus. We evaluated the toxicity of high-molecular-weight PEGs administered to Sprague Dawley rats. Groups of 12 rats per sex were administered subcutaneous injections of 20, 40, or 60 kDa PEG or intravenous injections of 60 kDa PEG at 100 mg PEG/kg body weight/injection once a week for 24 weeks. A significant decrease in triglycerides occurred in the 60 kDa PEG groups. PEG treatment led to a molecular-weight-related increase in PEG in plasma and a low level of PEG in cerebrospinal fluid. PEG was excreted in urine and feces, with a molecular-weight-related decrease in the urinary excretion. A higher prevalence of anti-PEG IgM was observed in PEG groups; anti-PEG IgG was not detected. PEG treatment produced a molecular-weight-related increase in vacuolation in the spleen, lymph nodes, lungs, and ovaries/testes, without an inflammatory response. Mast cell infiltration at the application site was noted in all PEG-treated groups. These data indicate that subcutaneous and intravenous exposure to high-molecular-weight PEGs produces anti-PEG IgM antibody responses and tissue vacuolation without inflammation.


Assuntos
Anticorpos/sangue , Formação de Anticorpos/efeitos dos fármacos , Plexo Corióideo/efeitos dos fármacos , Polietilenoglicóis/toxicidade , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Peso Molecular , Ratos , Ratos Sprague-Dawley
7.
PLoS Negl Trop Dis ; 16(1): e0010108, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35020729

RESUMO

BACKGROUND: In onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses. CONCLUSIONS/SIGNIFICANCE: The decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance.


Assuntos
Anticorpos/sangue , Mordeduras e Picadas de Insetos/epidemiologia , Saliva/imunologia , Simuliidae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Insetos Vetores/imunologia , Insetos Vetores/parasitologia , Masculino , Pessoa de Meia-Idade , Onchocerca volvulus/crescimento & desenvolvimento , Oncocercose/epidemiologia , Oncocercose/transmissão , Simuliidae/parasitologia , Adulto Jovem
8.
Br J Anaesth ; 128(3): 491-500, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980470

RESUMO

BACKGROUND: There is a need to assess the long-term outcomes of survivors of critical illness from COVID-19. METHODS: Ninety-two survivors of critical illness from COVID-19 from four hospitals in Hubei Province, China participated in this prospective cohort study. Multiple characteristics, including lung function (lung volumes, diffusing capacity for carbon monoxide, chest computed tomography scores, and walking capacity); immune status (SARS-CoV-2-neutralising antibody and all subtypes of immunoglobulin (Ig) G against SARS-CoV-2, immune cells in response to ex vivo antigen peptide stimuli, and lymphocyte count and its subtypes); liver, coagulation, and kidney functions; quality of life; cognitive function; and mental status, were assessed after 3, 6, and 12 months of follow-up. RESULTS: Amongst the 92 enrolled survivors, 72 (78%) patients required mechanical ventilation. At 12 months, the predicted percentage diffusing capacity of lung for carbon monoxide was 82% (inter-quartile range [IQR]: 76-97%) with a residual volume of 77 (64-88)%. Other lung function parameters and the 6-min walk test improved gradually over time and were almost back to normal by 12 months. The titres of IgG and neutralising antibody to COVID-19 remained high at 12 months compared with those of controls who were not infected with COVID-19, although IgG titres decreased significantly from 34.0 (IQR: 23.8-74.3) to 15.0 (5.8-24.3) AU ml-1 (P<0.001), whereas neutralising antibodies decreased from 29.99 (IQR: 19.43-53.93) AU ml-1 at 6 months to 19.75 (13.1-29.8) AU ml-1 (P<0.001) at 12 months. In general, liver, kidney, physical, and mental functions also improved over time. CONCLUSIONS: Survivors of critical illness from COVID-19 show some persistent long-term impairments in lung function. However, a majority of these tests were normal by 12 months. These patients still had detectable levels of neutralising antibodies against SARS-CoV-2 and all types of IgG at 12 months, but the levels had declined over this time period. CLINICAL TRIAL REGISTRATION: None.


Assuntos
Anticorpos/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Sobreviventes , Idoso , Anticorpos Neutralizantes/sangue , COVID-19/sangue , China , Estado Terminal , Citocinas/sangue , Feminino , Humanos , Rim/fisiopatologia , Fígado/fisiopatologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Testes de Função Respiratória , SARS-CoV-2/imunologia , Tomografia Computadorizada por Raios X , Teste de Caminhada
9.
J Fluoresc ; 32(2): 629-636, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35025017

RESUMO

The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85-1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN.


Assuntos
Fluorimunoensaio/métodos , Galectina 3/sangue , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/diagnóstico , Anticorpos/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Galectina 3/imunologia , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo
10.
J Thorac Cardiovasc Surg ; 163(1): 124-134.e8, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33012541

RESUMO

OBJECTIVE: Left ventricular assist device (LVAD) implantation has been shown to increase allosensitization before orthotopic heart transplantation, but the influence of LVAD support on posttransplant rejection is controversial. This study examines the postoperative incidence of acute cellular rejection (ACR) in patients bridged with continuous flow LVAD (CF-LVAD) relative to primary transplant (Primary Tx). METHODS: All patients who underwent orthotopic heart transplantation at our institution between July 2006 and March 2019 were retrospectively reviewed (n = 395). Patients were classified into Primary Tx (n = 145) and CF-LVAD (n = 207) groups. Propensity score matching on 13 covariates implemented a 0.1 caliper logistic model with nearest neighbor 1:1 matching. Development of moderate to severe (ie, 2R/3R) rejection was evaluated using a competing risks model. Potential predictors of 2R/3R ACR were evaluated using Fine-Gray regression on the marginal subdistribution hazard. RESULTS: Propensity score matching yielded 122 patients in each group (n = 244). At 12 and 24 months, the cumulative incidence of 2R/3R ACR was 17% and 23% for the CF-LVAD group and 26% and 31%, respectively, for the Primary Tx group (P = .170). CF-LVAD was not predictive of 2R/3R rejection on multivariable Fine-Gray regression (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.40-1.33; P = .301). There was no difference in the 5-year incidence of antibody mediated rejection (10% [n = 12] vs 9% [n = 11]; P = .827). CONCLUSIONS: After adjusting for covariates, CF-LVAD was not associated with an increased risk of moderate to severe ACR during the 24 months after cardiac transplantation. Further investigation is warranted with larger cohorts, but CF-LVAD may have minimal influence on posttransplant ACR.


Assuntos
Rejeição de Enxerto , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/estatística & dados numéricos , Efeitos Adversos de Longa Duração , Cuidados Pré-Operatórios , Medição de Risco , Anticorpos/sangue , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Humanos , Incidência , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/epidemiologia , Efeitos Adversos de Longa Duração/imunologia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/instrumentação , Cuidados Pré-Operatórios/métodos , Pontuação de Propensão , Modelos de Riscos Proporcionais , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Estados Unidos
11.
J Clin Rheumatol ; 28(1): e263-e269, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33843779

RESUMO

ABSTRACT: Antibodies are a fundamental tool to fight infections but are intrinsically built as a double-edged sword. One side recognizes the microbial antigen, and the other gives a call to arms to fight infection by recruiting immune cells and triggering inflammation. A balanced immune response must combine a potent neutralizing antibody and a swift disposal of the invading agent by innate immune cells with the least tissue damage possible. The longer the immune system takes to control the infection, the higher the possibility for a self-sustaining inflammatory process with potentially fatal consequences for the host. In addition to quantity, the quality of antibodies also matters, because posttranslational modifications altering the N-glycan composition in Fc fractions may help tilt the balance to the effector side, by modifying their affinity for Fc receptors in immune cells. The COVID-19 pandemic has provided a wealth of data bolstering our understanding of the rules governing the production of protective and nonprotective antibodies. Also, it has broadened our understanding of the role of viruses in triggering autoimmunity and inflammation, and widened our knowledge of the different mechanisms that can be activated by viral infection and lead to autoantibody production, inflammation, and progressive tissue damage. In addition, the COVID-19 infection has contributed a great deal to our comprehension of the role of antibodies in the causation of cytokine storms and systemic inflammatory response syndrome, also seen in patients with systemic autoimmune diseases.


Assuntos
COVID-19 , Reumatologistas , Anticorpos/sangue , Humanos , Pandemias , SARS-CoV-2
12.
J Neurol Neurosurg Psychiatry ; 93(1): 101-111, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34583946

RESUMO

OBJECTIVE: To describe onset clinical features predicting time to first relapse and time to long-term visual, motor and cognitive disabilities in paediatric-onset aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSDs). METHODS: In this retrospective UK multicentre cohort study, we recorded clinical data of paediatric-onset AQP4-IgG NMOSD. Univariate and exploratory multivariable Cox proportional hazard models were used to identify long-term predictors of permanent visual disability, Expanded Disability Status Scale (EDSS) score of 4 and cognitive impairment. RESULTS: We included 49 paediatric-onset AQP4-IgG patients (38.8% white, 34.7% black, 20.4% Asians and 6.1% mixed), mean onset age of 12±4.1 years, and 87.7% were female. Multifocal onset presentation occurred in 26.5% of patients, and optic nerve (47%), area postrema/brainstem (48.9%) and encephalon (28.6%) were the most involved areas. Overall, 52.3% of children had their first relapse within 1 year from disease onset. Children with onset age <12 years were more likely to have an earlier first relapse (p=0.030), despite showing no difference in time to immunosuppression compared with those aged 12-18 years at onset. At the cohort median disease duration of 79 months, 34.3% had developed permanent visual disability, 20.7% EDSS score 4 and 25.8% cognitive impairment. Visual disability was associated with white race (p=0.032) and optic neuritis presentations (p=0.002). Cognitive impairment was predicted by cerebral syndrome presentations (p=0.048), particularly if resistant to steroids (p=0.034). CONCLUSIONS: Age at onset, race, onset symptoms and resistance to acute therapy at onset attack predict first relapse and long-term disabilities. The recognition of these predictors may help to power future paediatric clinical trials and to direct early therapeutic decisions in AQP4-IgG NMOSD.


Assuntos
Aquaporina 4 , Pessoas com Deficiência/estatística & dados numéricos , Neuromielite Óptica/diagnóstico , Adolescente , Adulto , Idade de Início , Anticorpos/sangue , /estatística & dados numéricos , Encéfalo/patologia , Criança , Estudos de Coortes , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nervo Óptico/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Reino Unido , Adulto Jovem
13.
J Heart Lung Transplant ; 41(3): 365-372, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34895990

RESUMO

BACKGROUND: Sensitization, defined as the presence of circulating antibodies, presents challenges, particularly in patients undergoing heart transplantation (HTx) bridged with durable mechanical circulatory support (MCS). We aimed to investigate the post-transplantation outcomes of sensitized MCS patients. METHODS: Among 889 consecutively enrolled heart transplant (HTx) recipients between 2010 and 2018, 86 (9.7%) sensitized MCS patients (Group A) were compared with sensitized non-MCS patients (Group B, n = 189), non-sensitized MCS patients (Group C, n = 162), and non-sensitized non-MCS patients (Group D, n = 452) regarding post-HTx outcomes, including the incidence of primary graft dysfunction (PGD), 1-year survival, and 1-year freedom from antibody-mediated rejection (AMR). RESULTS: Sensitized MCS patients (Group A) showed comparable rates of PGD, 1-year survival, and 1-year freedom from AMR with Groups C and D. However, Group A showed significantly higher rates of 1-year freedom from AMR (95.3% vs 85.7%, p = 0.02) and an earlier decline in panel-reactive antibody (PRA) levels (p < 0.01) than sensitized non-MCS patients (Group B). Desensitization therapy effectively reduced the levels of PRA in both Groups A and B. When Group A was further divided according to the presence of preformed donor-specific antibodies (DSA), patients with preformed DSA showed significantly lower rates of 1-year freedom from AMR than those without (84.2% vs 98.5%, p = 0.01). CONCLUSIONS: Sensitized MCS patients showed significantly lower rates of AMR and an earlier decline in PRA levels following HTx than sensitized non-MCS patients. Removal of MCS at the time of transplantation might underlie these observations.


Assuntos
Anticorpos/sangue , Circulação Assistida , Transplante de Coração , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
14.
Rheumatol Int ; 41(12): 2133-2146, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34608531

RESUMO

Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) are a feature of the idiopathic inflammatory myopathies (IIM), but are also seen in other rheumatic diseases, and in individuals with no clinical symptoms. The aim of this study was to assess the clinical utility of MSA and MAA and in particular the clinical relevance of weakly positive results. We included all patients at our institution who had at least one positive result on the Immunoblot EUROLINE myositis panel over a 6-year period (2015-2020). Associations with clinical features and final diagnosis were evaluated. Eighty-seven of 225 (39%) myositis panel tests met the inclusion criteria. There were 52 strong positives and 35 weak positives for one or more MSA/MAAs. Among the strong positive group, 15% (8/52) were diagnosed with IIM, 34.6% (18/52) with interstitial lung disease, 7.7% (4/52) with anti-synthetase syndrome, 25% (13/52) with connective tissue disease, and others accounted for 25% (13/52). In weak-positive cases, only 14% (5/35) had connective tissue disease and none had IIM. 60% (21/35) of weak-positive cases were not associated with a specific rheumatic disease. A significant number of positive myositis panel results, particularly weak positives, are not associated with IIM or CTD.


Assuntos
Anticorpos/sangue , Miosite/imunologia , Adulto , Idoso , Anticorpos/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Feminino , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/diagnóstico , Estudos Retrospectivos
15.
Toxins (Basel) ; 13(12)2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34941703

RESUMO

Oral tolerance is defined as a specific suppression of cellular and humoral immune responses to a particular antigen through prior oral administration of an antigen. It has unique immunological importance since it is a natural and continuous event driven by external antigens. It is characterized by low levels of IgG in the serum of animals after immunization with the antigen. There is no report of induction of oral tolerance to Bothrops jararaca venom. Here, we induced oral tolerance to B. jararaca venom in BALB/c mice and evaluated the specific tolerance and cross-reactivity with the toxins of other Bothrops species after immunization with the snake venoms adsorbed to/encapsulated in nanostructured SBA-15 silica. Animals that received a high dose of B. jararaca venom (1.8 mg) orally responded by showing antibody titers similar to those of immunized animals. On the other hand, mice tolerized orally with three doses of 1 µg of B. jararaca venom showed low antibody titers. In animals that received a low dose of B. jararaca venom and were immunized with B. atrox or B. jararacussu venom, tolerance was null or only partial. Immunoblot analysis against the venom of different Bothrops species provided details about the main tolerogenic epitopes and clearly showed a difference compared to antiserum of immunized animals.


Assuntos
Reações Cruzadas/imunologia , Venenos de Crotalídeos/imunologia , Tolerância Imunológica , Administração Oral , Animais , Anticorpos/sangue , Bothrops , Venenos de Crotalídeos/administração & dosagem , Feminino , Camundongos Endogâmicos BALB C , Nanoestruturas , Dióxido de Silício/química , Especificidade da Espécie , Venenos de Víboras/imunologia , Viperidae
16.
Front Immunol ; 12: 765822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759933

RESUMO

Background: Eptinezumab is a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and is indicated for the preventive treatment of migraine in adults. This analysis characterizes the immunogenic profile of eptinezumab using data from clinical trials of eptinezumab for migraine prevention. Methods: Immunogenicity data were collected from five studies that included 2076 patients with episodic or chronic migraine treated with eptinezumab at dose levels ranging from 10 to 1000 mg, administered intravenously for up to 4 doses at 12-week intervals. Anti-drug antibody (ADA) results were available from 2074 of these patients. Four studies were randomized, double-blind, placebo-controlled trials with ADA monitoring for up to 56 weeks; one was a 2-year, open-label, phase 3 safety study with ADA monitoring for 104 weeks. Patients who had a confirmed ADA-positive result at the end-of-study visit were monitored for up to 6 additional months. Development of ADA and neutralizing antibodies (NAbs) were evaluated to explore three key areas of potential impact: pharmacokinetic exposure profile (eptinezumab trough plasma concentrations), efficacy (change in monthly migraine days), and safety (rates of treatment-emergent adverse events). These studies included methods designed to capture the dynamics of a potential humoral immune response to eptinezumab treatment, and descriptive analyses were applied to interpret the relationship of ADA signals to drug exposure, efficacy, and safety. Results: Pooled across the five clinical trials, treatment-emergent ADAs and NAbs occurred in 15.8 and 6.2% of eptinezumab-treated patients, respectively. Highly consistent profiles were observed across all studies, with initial onset of detectable ADA observed at the week 8 measurement and maximal ADA frequency and titer observed at week 24, regardless of eptinezumab dose level or number of doses. After 24 weeks, the ADA and NAb titers steadily declined despite additional doses of eptinezumab. Interpretation: Collectively, these integrated analyses did not demonstrate any clinically meaningful impact from ADA occurring after treatment with eptinezumab. The ADA profiles were low titer and transient, with the incidence and magnitude of ADA or NAb responses declining after week 24. Development of ADAs and NAbs did not impact the efficacy and safety profiles of eptinezumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos/sangue , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Transtornos de Enxaqueca/prevenção & controle , Anticorpos/imunologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/farmacocinética , Método Duplo-Cego , Humanos , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/imunologia , Transtornos de Enxaqueca/metabolismo , Resultado do Tratamento
17.
Cells ; 10(11)2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34831411

RESUMO

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn's disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).


Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/microbiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Anticorpos/sangue , Biodiversidade , Estudos de Casos e Controles , Feminino , Fungos/genética , Microbioma Gastrointestinal/genética , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/cirurgia , Interleucina-17/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Metagenômica , RNA Ribossômico 16S/genética , Índice de Gravidade de Doença
18.
Asian Pac J Cancer Prev ; 22(10): 3309-3315, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34711008

RESUMO

BACKGROUND: Asparaginase is one of the essential chemotherapies used to treat acute lymphoblastic leukemia (ALL). Asparaginase antibody production may cause a subtherapeutic level and result in an inferior outcome. The aim of this study was to prove the efficacy of current native E.coli asparaginase-based protocol. Moreover, does subtherapeutic result appeared in small group of the trial?. METHODS: A prospective study of asparaginase activity among patients who received native E.coli asparaginase 10,000 IU/m2 intramuscularly according to The Thai Pediatric Oncology Group (ThaiPOG) protocol was done. The plasma asparaginase activity was measured by the coupled enzymatic reaction. Pharmacokinetic data including peak activity (Cmax), time to maximum concentration (Tmax), area under the curve (AUC0-48h) being elucidated. RESULTS: Eight patients (five males and three females), median age 9.5 years, were enrolled. The median asparaginase activity of seven cases who were eligible for calculation reached Tmax within 24 hours (range 6-48 hours) with mean±SD of Cmax 3.60±0.34 (range 3.02-4.11) IU/ml. Mean±SD of AUC0-48h is 143.23±36.94 IU.h/mL (range 71.07 - 180.12 IU.h/mL). The post-48-hour activity showed a mean±SD of 3.19±0.24 IU/ml (range 2.77-3.51 IU/ml) which implied an adequacy of activity over 48 hours and proper for the 12-day period. One relapsed ALL patient showed an extremely low AUC of asparaginase activity which coincided with urticaria after asparaginase injection. Subsequently, the asparaginase antibody was demonstrated in this patient. CONCLUSION: Native E. coli asparaginase-based protocol provides a compelling pharmacokinetic effect. Asparaginase activity and/or antibody testing is recommended for all cases especially in a relapsed patient, history of high accumulative dose of asparaginase or suspected allergic reaction. Patients with low asparaginase activity or allergy may benefit from switching to an alternative form of asparaginase to maintain treatment efficacy.


Assuntos
Antineoplásicos/farmacocinética , Asparaginase/farmacocinética , Escherichia coli/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Anticorpos/sangue , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Área Sob a Curva , Asparaginase/administração & dosagem , Asparaginase/sangue , Asparaginase/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Injeções Intramusculares , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Prospectivos , Fatores de Tempo , Urticária/induzido quimicamente
19.
Cells ; 10(10)2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34685647

RESUMO

Neutrophil extracellular traps (NETs) are macromolecular structures programmed to trap circulating bacteria and viruses. The accumulation of NETs in the circulation correlates with the formation of anti-double-stranded (ds) DNA antibodies and is considered a causative factor for systemic lupus erythematosus (SLE). The digestion of DNA by DNase1 and DNases1L3 is the rate- limiting factor for NET accumulation. Mutations occurring in one of these two DNase genes determine anti-DNA formation and are associated with severe Lupus-like syndromes and lupus nephritis (LN). A second mechanism that may lead to DNase functional impairment is the presence of circulating DNase inhibitors in patients with low DNase activity, or the generation of anti-DNase antibodies. This phenomenon has been described in a relevant number of patients with SLE and may represent an important mechanism determining autoimmunity flares. On the basis of the reviewed studies, it is tempting to suppose that the blockade or selective depletion of anti-DNase autoantibodies could represent a potential novel therapeutic approach to prevent or halt SLE and LN. In general, strategies aimed at reducing NET formation might have a similar impact on the progression of SLE and LN.


Assuntos
Autoimunidade , Desoxirribonucleases/metabolismo , Armadilhas Extracelulares/metabolismo , Animais , Anticorpos/sangue , Autoimunidade/genética , DNA/sangue , Desoxirribonucleases/antagonistas & inibidores , Desoxirribonucleases/genética , Humanos , Mutação/genética
20.
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
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