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2.
Arthroplast Today ; 25: 101286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38292146

RESUMO

Background: Robotic-assisted orthopaedic surgery has become popular and widely available, mainly for total joint arthroplasty. However, there has been a persistent concern regarding access to robotic-assisted surgery and the utilization rate of total joint arthroplasty among minority groups. As an imperative effort to close the gap regarding health inequalities, we assessed the knowledge and perspective of Hispanics regarding robotic-assisted orthopaedic surgery. Methods: A 28-item questionnaire was established to evaluate Hispanics' perceptions of robotic-assisted orthopaedic surgery. Participants answered questions about demographic features, knowledge about robotic-assisted orthopaedic surgery, and preferences regarding manual vs robotic-assisted procedures. Results: A total of 580 questionnaires were analyzed in our study, with an average age of participants of 49.1 years. Only 44.2% of the participants were familiar with robotic-assisted orthopaedic surgery. Fifty-three percent of the respondents preferred robotic-assisted surgery over conventional procedures, with many participants believing that robotic-assisted surgery leads to better outcomes (54.7%) and faster recovery (53.1%). Conclusions: Knowledge about specific factors such as clinical outcomes and costs may influence the perception and preference of Hispanics toward robotic-assisted orthopaedic surgery. Therefore, patient education may play a crucial role in the informed decision-making process in Hispanics when opting between robotic-assisted or traditional orthopaedic surgery.

3.
Int J Surg Case Rep ; 112: 108986, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37890236

RESUMO

INTRODUCTION AND IMPORTANCE: Fractures in the proximal tibial tuberosity are rare injuries. Even more uncommon are bilateral simultaneous fractures. Due to the few cases reported in the literature, we aimed to present a case which may contribute to the diagnosis and treatment of bilateral simultaneous tibial tubercle fractures. CASE PRESENTATION: A 13-year-old Hispanic male presented to the emergency department after experiencing sudden knee buckling while running after standing up from the catcher's position (squatted) during a baseball game, causing him to collapse to the ground. Plain radiographs revealed displaced tibial tubercle avulsion fractures in both knees. He underwent bilateral open reduction and internal fixation. Fracture healing was completed without complications. DISCUSSION: To the best of our knowledge, this is the first documented case of a Hispanic pediatric baseball player, adding to the small number of reported cases of bilateral tibial tubercle fractures. The presented case is rare in terms of the mechanism of injury, which has been scantly reported in the literature. CONCLUSION: Due to the rarity of atraumatic bilateral tibial tubercle fractures we believe this documentation may be of clinical relevance.

4.
J Bioinform Syst Biol ; 5(1): 1-25, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36382242

RESUMO

In recent years, transcriptomic databases have become one of the main sources for protein discovery. In our studies of nervous system and digestive tract regeneration in echinoderms, we have identified several transcripts that have attracted our attention. One of these molecules corresponds to a previously unidentified transcript (Orpin) from the sea cucumber Holothuria glaberrima that appeared to be upregulated during intestinal regeneration. We have now identified a second highly similar sequence and analyzed the predicted proteins using bioinformatics tools. Both sequences have EF-hand motifs characteristic of calcium-binding proteins (CaBPs) and N-terminal signal peptides. Sequence comparison analyses such as multiple sequence alignments and phylogenetic analyses only showed significant similarity to sequences from other echinoderms or from hemichordates. Semi-quantitative RT-PCR analyses revealed that transcripts from these sequences are expressed in various tissues including muscle, haemal system, gonads, and mesentery. However, contrary to previous reports, there was no significant differential expression in regenerating tissues. Nonetheless, the identification of unique features in the predicted proteins and their presence in the holothurian draft genome suggest that these might comprise a novel subfamily of EF-hand containing proteins specific to the Ambulacraria clade.

5.
Curr Opin Pediatr ; 34(6): 580-588, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36165614

RESUMO

PURPOSE OF REVIEW: The current review highlights how inborn errors of immunity (IEI) due to IL-2 receptor (IL-2R) subunit defects may result in children presenting with a wide variety of infectious and inflammatory presentations beyond typical X-linked severe combined immune deficiency (X-SCID) associated with IL-2Rγ. RECENT FINDINGS: Newborn screening has made diagnosis of typical SCID presenting with severe infections less common. Instead, infants are typically diagnosed in the first days of life when they appear healthy. Although earlier diagnosis has improved clinical outcomes for X-SCID, atypical SCID or other IEI not detected on newborn screening may present with more limited infectious presentations and/or profound immune dysregulation. Early management to prevent/control infections and reduce inflammatory complications is important for optimal outcomes of definitive therapies. Hematopoietic stem cell transplant (HSCT) is curative for IL-2Rα, IL-2Rß, and IL-2Rγ defects, but gene therapy may yield comparable results for X-SCID. SUMMARY: Defects in IL-2R subunits present with infectious and inflammatory phenotypes that should raise clinician's concern for IEI. Immunophenotyping may support the suspicion for diagnosis, but ultimately genetic studies will confirm the diagnosis and enable family counseling. Management of infectious and inflammatory complications will determine the success of gene therapy or HSCT.


Assuntos
Receptores de Interleucina-2 , Imunodeficiência Combinada Severa , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X , Humanos , Homeostase , Subunidade alfa de Receptor de Interleucina-2 , Receptores de Interleucina-2/genética , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia , Recém-Nascido
6.
Nat Immunol ; 23(8): 1256-1272, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35902638

RESUMO

The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent 'domino effect' that impacts stringency of tolerance and B cell fate in the periphery.


Assuntos
Linfócitos B , Proteínas de Ligação a DNA , Proteínas de Homeodomínio , Proteínas Nucleares , Diferenciação Celular , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Proteínas de Homeodomínio/genética , Humanos , Tolerância Imunológica , Contagem de Linfócitos , Proteínas Nucleares/deficiência
7.
Curr Opin Immunol ; 72: 298-308, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34479098

RESUMO

Although IL-2 was first recognized as growth factor for T cells, it is now also appreciated to be a key regulator of T cells through its effects on regulatory T cells (Treg). The IL-2 receptor (IL-2R) subunits' different (i) ligand affinities, (ii) dimerization or trimerization relationships with other cytokine subunits, (iii) expression across multiple cell types, and (iv) downstream signaling effects, largely dictate cellular tolerance and antimicrobial processes. Defects in IL-2Rγ result in profound and almost universally fatal immune deficiency, unless treated with hematopoietic stem cell transplantation (HSCT). Defects in IL-2Rα and IL-2Rß result in more limited infection susceptibility, particularly to herpesviruses. However, the most prominent clinical symptomatology for IL-2Rα and IL-2Rß defects include multi-organ autoimmunity and inflammation, consistent with the critical role of IL-2 in establishing and maintaining immune tolerance. Here, we review how we have arrived at our current understanding of the complex roles of IL-2/2R in host defense and tolerance focusing on the insights gained from human clinical immunology.


Assuntos
Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Tolerância Imunológica , Receptores de Interleucina-2/genética , Receptores de Interleucina-2/metabolismo , Animais , Autoimunidade , Resistência à Doença/genética , Resistência à Doença/imunologia , Humanos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
8.
Lab Invest ; 100(4): 516-526, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31857699

RESUMO

Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most mast cell-deficient models have been available only on a single genetic background. We transferred the KitW-sh allele onto the BALB/c background to generate BALB/c mast cell-deficient mice (BALB/c-KitW-sh/W-sh). BALB/c-KitW-sh/W-sh mice have dramatically reduced mast cell numbers (0-2% of wild type) in all tissues examined, as well as subtle hematologic differences from the corresponding wild type mice, including splenomegaly with evidence of increased splenic hematopoiesis. We examined in BALB/c-KitW-sh/W-sh mice models of allergic inflammation that are substantially diminished in C57BL/6-KitW-sh/W-sh mast cell-deficient mice. In a model of acute allergic inflammation, i.e., IgE-dependent passive cutaneous anaphylaxis, both ear swelling and leukocyte infiltration were largely or entirely absent in BALB/c-KitW-sh/W-sh mice. In contrast, in two different models of allergic airway inflammation, airway hyperresponsiveness, lung inflammation, and airway remodeling developed robustly in mast cell-deficient BALB/c-KitW-sh/W-sh mice. These results support the conclusion that the importance of mast cell contributions in various models of allergic inflammation may be at least partially determined by genetic background.


Assuntos
Asma , Modelos Animais de Doenças , Animais , Asma/induzido quimicamente , Asma/patologia , Asma/fisiopatologia , Mastócitos/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-kit/genética
10.
J Allergy Clin Immunol Pract ; 7(6): 1970-1985.e4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30877075

RESUMO

BACKGROUND: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.


Assuntos
Proteínas de Homeodomínio , Síndromes de Imunodeficiência , Adolescente , Adulto , Autoimunidade , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Imunossupressores/uso terapêutico , Lactente , Inflamação , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
12.
J Allergy Clin Immunol Pract ; 6(6): 2178, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30390915
13.
Pediatr Allergy Immunol Pulmonol ; 31(3): 158-165, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30283713

RESUMO

Background: The prevalence and impact of allergic and immune-mediated food disorders in pediatric acute-onset neuropsychiatric syndrome (PANS) are mostly unknown. Objective: We sought to explore the prevalence of atopic dermatitis (AD), asthma, allergic rhinitis (AR), IgE-mediated food allergies (FAs), and other immune-mediated food disorders requiring food avoidance in patients with PANS. In addition, to further understand the extent of food restriction in this population, we investigated the empiric use of dietary measures to improve PANS symptoms. Methods: Pediatric patients in a PANS Clinic and Research Program were given surveys regarding their caregiver burdens, allergic and food-related medical history, and whether food elimination resulted in perception of improvement of PANS symptoms. A review of health records was conducted to confirm that all responses in the survey were concordant with documentation of each patient's medical chart. Results: Sixty-nine (ages 4-20 years) of 80 subjects who fulfilled PANS criteria completed the surveys. Thirteen (18.8%) had AD, 11 (15.9%) asthma, 33 (47.8%) AR, 11 (15.9%) FA, 1 (1.4%) eosinophilic gastrointestinal disorders, 1 (1.4%) food protein-induced enterocolitis syndrome, 3 (4.3%) milk protein-induced proctocolitis syndrome, and 3 (4.3%) celiac disease. Thirty subjects (43.5%) avoided foods due to PANS; elimination of gluten and dairy was most common and was associated with perceived improvement of PANS symptoms (by parents). This perceived improvement was not confirmed with objective data. Conclusions: The prevalence of allergic and immune-mediated food disorders in PANS is similar to the general population as reported in the literature, with the exception of AR that appears to be more prevalent in our PANS cohort. More research will be required to establish whether diet or allergies influence PANS symptoms.

14.
Transl Pediatr ; 7(1): 14-22, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29441279

RESUMO

BACKGROUND: Limited therapeutic options are available for Fontan patients with dysfunctional or failing single ventricle physiology. This study describes the evaluation of an alternative, non-invasive, at-home therapeutic compression treatment for Fontan patients. Our hypothesis is that routinely administered, externally applied compression treatments to the lower extremities will augment systemic venous return, improve ventricular preload, and thus enhance cardiac output in Fontan patients. METHODS: To initially evaluate this hypothesis, we employed the NormaTec pneumatic compression device (PCD) in a pilot clinical study (n=2). This device is composed of inflatable trouser compartments that facilitate circumferentially and uniformly applied pressure to a patient's lower extremities. Following an initial health screening, test subjects were pre-evaluated with a modified-Bruce treadmill exercise stress test, and baseline data on cardiorespiratory health was collected. After training, test subjects conducted 6 days of external compression therapy at-home. Subjects were then re-evaluated with a final treadmill stress test and data acquisition of new cardiorespiratory parameters. RESULTS: Both subjects demonstrated improvement in exercise duration time, peak oxygen volume, and ventilator threshold, as compared to the baseline evaluation. CONCLUSIONS: These findings are promising and provide the foundation for future studies that will focus on increasing study participation (sample size) to better assess the clinical benefit of compression therapy for Fontan patients.

16.
J Allergy Clin Immunol ; 140(2): 335-348, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28780941

RESUMO

Anaphylaxis is a severe systemic hypersensitivity reaction that is rapid in onset; characterized by life-threatening airway, breathing, and/or circulatory problems; and usually associated with skin and mucosal changes. Because it can be triggered in some persons by minute amounts of antigen (eg, certain foods or single insect stings), anaphylaxis can be considered the most aberrant example of an imbalance between the cost and benefit of an immune response. This review will describe current understanding of the immunopathogenesis and pathophysiology of anaphylaxis, focusing on the roles of IgE and IgG antibodies, immune effector cells, and mediators thought to contribute to examples of the disorder. Evidence from studies of anaphylaxis in human subjects will be discussed, as well as insights gained from analyses of animal models, including mice genetically deficient in the antibodies, antibody receptors, effector cells, or mediators implicated in anaphylaxis and mice that have been "humanized" for some of these elements. We also review possible host factors that might influence the occurrence or severity of anaphylaxis. Finally, we will speculate about anaphylaxis from an evolutionary perspective and argue that, in the context of severe envenomation by arthropods or reptiles, anaphylaxis might even provide a survival advantage.


Assuntos
Anafilaxia/imunologia , Anafilaxia/genética , Animais , Modelos Animais de Doenças , Variação Genética , Humanos
17.
J Child Adolesc Psychopharmacol ; 27(7): 629-639, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28714753

RESUMO

BACKGROUND: Sudden-onset severe obsessive-compulsive symptoms and/or severely restrictive food intake with at least two coinciding, similarly debilitating neuropsychiatric symptoms define Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). When associated with Group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). An abnormal immune response to infection and subsequent neuroinflammation is postulated to play an etiologic role. Most patients have a relapsing-remitting course. Treatment outcome data for youth with PANS and PANDAS are limited. METHODS: One hundred seventy-eight consecutive patients were seen in the Stanford PANS clinic between September 1, 2012 and January 15, 2016, of whom 98 met PANS or PANDAS criteria, had a single episode of PANS or relapsing/remitting course, and collectively experienced 403 flares. Eighty-five flares were treated with 102 total courses of oral corticosteroids of either short (4-5 days) or long (5 days-8 weeks) duration. Response to treatment was assessed within 14 days of initiating a short burst of corticosteroids and at the end of a long burst based on clinician documentation and patient questionnaires. Data were analyzed by using multilevel random-effects models. RESULTS: Patients experienced shorter flares when treated with oral corticosteroids (6.4 ± 5.0 weeks vs. 11.4 ± 8.6 weeks) than when not treated (p < 0.001), even after controlling for presumed confounding variables, including age at flare, weeks since onset of PANS illness, sex, antibiotic treatment, prophylactic antibiotics, previous immunomodulatory treatment, maintenance anti-inflammatory therapy, psychiatric medications, and cognitive behavioral therapy (p < 0.01). When corticosteroids were given for the initial PANS episode, flares tended to be shorter (10.3 ± 5.7 weeks) than when not treated (16.5 ± 9.6 weeks) (p = 0.06). This difference was statistically significant after controlling for the relevant confounding variables listed earlier (p < 0.01). Earlier use of corticosteroids was associated with shorter flare durations (p < 0.001). Longer courses of corticosteroids were associated with a more enduring impact on the duration of neuropsychiatric symptom improvement (p = 0.014). CONCLUSION: Corticosteroids may be a helpful treatment intervention in patients with new-onset and relapsing/remitting PANS and PANDAS, hastening symptom improvement or resolution. When corticosteroids are given earlier in a disease flare, symptoms improve more quickly and patients achieve clinical remission sooner. Longer courses of corticosteroids may result in more durable remissions. A double-blind placebo-controlled clinical trial of corticosteroids in PANS is warranted to formally assess treatment efficacy.


Assuntos
Corticosteroides/administração & dosagem , Doenças Autoimunes/tratamento farmacológico , Transtornos do Comportamento Infantil/tratamento farmacológico , Serviços de Saúde Comunitária/métodos , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Doença Aguda , Administração Oral , Instituições de Assistência Ambulatorial , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Criança , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/epidemiologia , Pré-Escolar , Feminino , Humanos , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/epidemiologia , Estudos Retrospectivos , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia
18.
J Child Adolesc Psychopharmacol ; 27(7): 574-593, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36358107

RESUMO

Introduction: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a clinically heterogeneous disorder with a number of different etiologies and disease mechanisms. Inflammatory and postinfectious autoimmune presentations of PANS occur frequently, with some clinical series documenting immune abnormalities in 75%-80% of patients. Thus, comprehensive treatment protocols must include immunological interventions, but their use should be reserved only for PANS cases in which the symptoms represent underlying neuroinflammation or postinfectious autoimmunity, as seen in the PANDAS subgroup (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections). Methods: The PANS Research Consortium (PRC) immunomodulatory task force is comprised of immunologists, rheumatologists, neurologists, infectious disease experts, general pediatricians, psychiatrists, nurse practitioners, and basic scientists with expertise in neuroimmunology and PANS-related animal models. Preliminary treatment guidelines were created in the Spring of 2014 at the National Institute of Health and refined over the ensuing 2 years over conference calls and a shared web-based document. Seven pediatric mental health practitioners, with expertise in diagnosing and monitoring patients with PANS, were consulted to create categories in disease severity and critically review final recommendations. All authors played a role in creating these guidelines. The views of all authors were incorporated and all authors gave final approval of these guidelines. Results: Separate guidelines were created for the use of immunomodulatory therapies in PANS patients with (1) mild, (2) moderate-to-severe, and (3) extreme/life-threatening severity. For mildly impairing PANS, the most appropriate therapy may be "tincture of time" combined with cognitive behavioral therapy and other supportive therapies. If symptoms persist, nonsteroidal anti-inflammatory drugs and/or short oral corticosteroid bursts are recommended. For moderate-to-severe PANS, oral or intravenous corticosteroids may be sufficient. However, intravenous immunoglobulin (IVIG) is often the preferred treatment for these patients by most PRC members. For more severe or chronic presentations, prolonged corticosteroid courses (with taper) or repeated high-dose corticosteroids may be indicated. For PANS with extreme and life-threatening impairment, therapeutic plasma exchange is the first-line therapy given either alone or in combination with IVIG, high-dose intravenous corticosteroids, and/or rituximab. Conclusions: These recommendations will help guide the use of anti-inflammatory and immunomodulatory therapy in the treatment of PANS.

19.
Nat Commun ; 7: 13696, 2016 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-27982078

RESUMO

Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support TH2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG1 and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.


Assuntos
Asma/induzido quimicamente , Asma/metabolismo , Mastócitos/fisiologia , Receptores de IgE/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Remodelação das Vias Aéreas , Animais , Anticorpos , Antígenos de Dermatophagoides/imunologia , Antígenos de Dermatophagoides/toxicidade , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genótipo , Imunoglobulina E , Imunoglobulina G , Camundongos , Camundongos Knockout , Ovalbumina/imunologia , Ovalbumina/toxicidade , Receptores de IgE/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/genética
20.
Curr Opin Allergy Clin Immunol ; 16(6): 549-556, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27749361

RESUMO

PURPOSE OF REVIEW: This review gives an overview of the systems-immunology single-cell proteomic and transcriptomic approaches that can be applied to study primary immunodeficiency. It also introduces recent advances in multiparameter tissue imaging, which allows extensive immune phenotyping in disease-affected tissue. RECENT FINDINGS: Mass cytometry is a variation of flow cytometry that uses rare earth metal isotopes instead of fluorophores as tags bound to antibodies, allowing simultaneous measurement of over 40 parameters per single-cell. Mass cytomety enables comprehensive single-cell immunophenotyping and functional assessments, capturing the complexity of the immune system, and the molecularly heterogeneous consequences of primary immunodeficiency defects. Protein epitopes and transcripts can be simultaneously detected allowing immunophenotype and gene expression evaluation in mixed cell populations. Multiplexed epitope imaging has the potential to provide extensive phenotypic characterization at the subcellular level, in the context of 3D tissue microenvironment. SUMMARY: Mass cytometry and multiplexed epitope imaging can complement genetic methods in diagnosis and study of the pathogenesis of primary immunodeficiencies. The ability to understand the effect of a specific defect across multiple immune cell types and pathways, and in affected tissues, may provide new insight into tissue-specific disease pathogenesis and evaluate effects of therapeutic interventions.


Assuntos
Perfilação da Expressão Gênica/métodos , Síndromes de Imunodeficiência/diagnóstico , Espectrometria de Massas , Proteogenômica/métodos , Animais , Humanos , Imageamento Tridimensional , Imunofenotipagem , Metais , Análise de Célula Única/métodos
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