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2.
Life Sci ; 242: 117223, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881222

RESUMO

Acute lymphoblastic leukemia (ALL) is an aggressive cancer in children and adults which possess higher CD47 expression than normal cells. ALL chemotherapy has a lot of side effects and in most cases is ineffective. However arrival of Natural killer (NK) cell immunotherapy raised hopes for successful treatment of cancers, tailoring NK cells to meet clinical requirements is still under investigation. Of note, CD16+ (FCγIIIa) NK cells eliminate tumor cells with antibody dependent cell cytotoxicity (ADCC) mechanism. Therefore, we evaluated ADCC effect of cord blood stem cell derived CD16+ NK cells with using anti CD47 blocking antibody. CD16+ NK cells generated efficiently from CD34 positive cord blood cells in vitro using IL-2, IL-15 and IL-21 cytokines, although it was not dose dependent. CD16+ cells derived from CD34+ cells in day 14 of culture efficiently increased apoptosis in ALL cells, produced INFγ and increased CD107-a expression when used anti CD47 antibody (increased around 30-40%). Interestingly, CD16+ NK cell cytotoxicity slightly increased in combination with macrophages against ALL cells (around 10%). Taken together, our findings induced this hope that cord blood stem cell derived CD16+ NK cells exploit antitumor immune response in cancer therapy with using anti-CD47 antibody.


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Antígeno CD47/imunologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Células Matadoras Naturais/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de IgG/imunologia , Anticorpos Anti-Idiotípicos/imunologia , Western Blotting , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Imunoterapia/métodos , Microscopia de Fluorescência , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
3.
Int J Pediatr Otorhinolaryngol ; 127: 109674, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31526939

RESUMO

OBJECTIVES: To review the efficacy of anti-IgE therapy in allergic rhinitis (AR). METHODS: Literature search was performed using the PubMed and Proquest Central databases at Kirikkale University Library. RESULTS: Although the skin prick testing in patients suffering from AR is positive (indicating that antigen-specific Immunoglobulin E has been produced), there is no association with overall circulating IgE levels. Correlation was lacking between circulating IgE level and either skin prick tests or laboratory testing for specific IgE. Omalizumab binds to uncomplexed IgE in man more avidly than does Fc-epsilon. The effect of omalizumab is to lower the level of IgE and downgrade production of FceRI receptors (which bind IgE) in mast cells and basophils, causing less mast cell recruitment and responsivity and thus diminishing eosinophilic infiltration and activation. Anti-IgE therapy through omalizumab may shorten the lifetime of mast cells and causes dendritic cells to downgrade their production of FcεRI. There are reports indicating benefit from omalizumab in managing food allergies, nasal polyp formation, essential anaphylaxis, AR, venom allergy and eczema. Omalizumab acts to lessen circulating IgE levels, whilst reducing production of FceRI by mast cells and basophils. The fact that omalizumab influences how eosinophils respond may be down to disruption of the antigen-IgE-mast cell interactions, with mast cells being recruited at lower levels and thus chemotactic eosinophilic recruitment via cytokines being greatly reduced. Omalizumab has the effect in cases of perennial AR of blocking the increased eosinophilic recruitment and tissue infiltration initiated by seasonal antigens. Likewise, in omalizumab-treated cases, circulating unbound IgE levels showed significant decreases. For patients with perennial AR, the average daily nasal severity score was significantly reduced where omalizumab was administered, compared to placebo. CONCLUSION: Omalizumab has efficacy in ameliorating symptoms and reduces the necessity for additional medication in both seasonal and perennial allergic rhinitis.


Assuntos
Antialérgicos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Imunoglobulina E/sangue , Imunoterapia , Omalizumab/uso terapêutico , Rinite Alérgica/terapia , Basófilos/imunologia , Eosinófilos/imunologia , Humanos , Imunoglobulina E/imunologia , Rinite Alérgica/imunologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-30648914

RESUMO

Diacylglycerol kinase (DGK) is responsible for the enzymatic conversion of diacylglycerol (DG) to phosphatidic acid (PA). Both DG and PA serve as signaling molecules; therefore, DGK functions as a key enzyme between DG- and PA-mediated signaling. DGKα, one of the 10 DGK isozymes, is involved in T cell function and has been shown to localize in the cytoplasm and nucleus. Furthermore, DGKα translocates to the plasma membrane in response to T cell receptor stimulation. Recently, we developed a specific monoclonal antibody (mAb), DaMab-2 (mouse IgG1, kappa), against DGKα. DaMab-2 is very useful in immunocytochemical analysis using HeLa cells. In this study, we characterized the binding epitope of DaMab-2 using Western blot and revealed that Cys246, Lys249, Pro252, and Cys253 of DGKα are important for DaMab-2 binding to the DGKα protein. Our findings can be applied for the production of more functional anti-DGKα mAbs.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais/imunologia , Diacilglicerol Quinase/imunologia , Epitopos/imunologia , Aminoácidos/imunologia , Anticorpos Anti-Idiotípicos/genética , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/uso terapêutico , Diacilglicerol Quinase/antagonistas & inibidores , Diacilglicerol Quinase/química , Diacilglicerol Quinase/genética , Mapeamento de Epitopos/métodos , Epitopos/química , Células HeLa , Humanos , Ácidos Fosfatídicos/química , Ácidos Fosfatídicos/imunologia , Ligação Proteica , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais , Linfócitos T/imunologia
8.
Int J Biol Macromol ; 124: 17-24, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30471391

RESUMO

Epidermal growth factor receptor variant III (EGFRvIII) is known to be specifically expressed in cancer cells and associated with tumor virulence. The receptor provides an opportunity for both specifically targeting the tumor cells as well as for potentially controlling and inhibiting tumor progression. In this study, humanized anti-EGFRvIII single-chain fragment variable (hscFv) was expressed in insect cell culture system to accommodate post-translational glycosylations crucial for the fragment stability and efficacy. Target specific binding of the developed fragment to EGFRvIII expressing cell lines and EGFRvIII positive glioblastoma patient samples was evaluated by immunocytochemistry and immunohistochemistry respectively. Downstream intracellular signaling mechanisms related to the action of the developed antibody fragment on growth/metabolism of the cell was evaluated in U87-EGFRvIII human glioblastoma cell lines. It was observed that the hscFv bound specifically to EGFRvIII in mutant expressing cells. Functionally, hscFv was found to confer anti-proliferative properties in EGFRvIII expressing cell lines by downregulating phosphorylation of EGFR/EGFRvIII, Lyn, PI3K and GLUT3 involved in proliferation and metabolism. This study demonstrated the significance of hscFv as a potential immunotherapeutic agent as well as a targeting agent for specific delivery of drugs to EGFRvIII expressing cancer cells.


Assuntos
Glioblastoma/imunologia , Imunoterapia , Anticorpos de Cadeia Única/imunologia , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Baculoviridae/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Receptores ErbB/imunologia , Receptores ErbB/uso terapêutico , Regulação da Expressão Gênica/imunologia , Glioblastoma/terapia , Transportador de Glucose Tipo 3/genética , Humanos , Fosforilação , Anticorpos de Cadeia Única/biossíntese , Anticorpos de Cadeia Única/uso terapêutico
9.
Curr Opin Allergy Clin Immunol ; 18(5): 425-431, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30015639

RESUMO

PURPOSE OF REVIEW: Symptomatic management of chronic spontaneous urticaria (CSU) basically depends on second-generation H1 antihistamines and omalizumab. Omalizumab is a game changer in the management, but still there is a need for new targets and new biologics targeting new pathways in the treatment which will provide long-lasting remission, which will be given orally and which will be cheaper. This review will focus on new biologics that are underway of production or are already under use for different disorders but could be beneficial for the treatment of Chronic urticaria. RECENT FINDINGS: In this review, the treatment targets are classified according to the cells which are involved in the pathogenesis of CSU. Those are mast cells/basophils, B cells, T cells and eosinophils. The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab. SUMMARY: The ongoing clinical trials on new targets of treatment hold new hopes not only for a better care of the disease but also a better understanding of the pathomechanisms lying underneath.


Assuntos
Antialérgicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Urticária/tratamento farmacológico , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD/uso terapêutico , Antígenos de Diferenciação de Linfócitos B/uso terapêutico , Linfócitos B/imunologia , Basófilos/imunologia , Produtos Biológicos/uso terapêutico , Doença Crônica , Eosinófilos/imunologia , Humanos , Imunoglobulina E/imunologia , Interleucina-1/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Lectinas/uso terapêutico , Mastócitos/imunologia , Terapia de Alvo Molecular , Omalizumab/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Quinase Syk/antagonistas & inibidores , Linfócitos T/imunologia , Urticária/imunologia
10.
JAAPA ; 31(7): 22-26, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29889715

RESUMO

Chronic idiopathic urticaria (CIU), also known as chronic spontaneous urticaria, is characterized by the presence of hives on most days of the week, for 6 weeks or longer, and without an identifiable or consistent cause. Evaluation is clinical and based on the presence of episodic urticarial lesions. Although patients are subject to overtesting during the diagnosis of CIU, guidelines suggest starting with three basic laboratory tests. Treatment is a stepwise approach, involving second-generation antihistamines, histamine2 antagonists, leukotriene receptor antagonists, first-generation antihistamines, and potent antihistamines. Refractory CIU requires adding alternative agents such as omalizumab, anti-inflammatory agents, and immunosuppressants.


Assuntos
Antialérgicos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Urticária/tratamento farmacológico , Adulto , Doença Crônica , Quimioterapia Combinada , Humanos , Urticária/prevenção & controle
11.
J Int Adv Otol ; 14(1): 144-147, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29764789

RESUMO

Eosinophilic otitis media (EOM) are intractable otitis media characterized by highly viscous secretions containing eosinophils in the middle ear. They are resistant to conventional medication and surgery. This condition occurs primarily in patients with bronchial asthma or allergic rhinitis and is often complicated by rhinosinusitis. Systemic and topical steroid therapies are effective treatments. However, long-term steroid therapy is often limited by a high risk of serious adverse effects. The use of topical steroids and otorrhea are bothersome when wearing hearing aids. Here, we report a case of intractable otitis media due to EOM. Otorrhea was controlled with topical steroids. Bone conduction hearing was stable for an extended period with anti-IgE monoclonal antibodies (omalizumab). An implantable bone conduction hearing aid was used for rehabilitation of conductive hearing loss.


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Condução Óssea/fisiologia , Orelha Média/efeitos dos fármacos , Otite Média com Derrame/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Prótese Ancorada no Osso/efeitos adversos , Orelha Média/imunologia , Orelha Média/patologia , Eosinofilia/fisiopatologia , Eosinófilos/imunologia , Feminino , Auxiliares de Audição/efeitos adversos , Perda Auditiva/etiologia , Humanos , Fatores Imunológicos/uso terapêutico , Pessoa de Meia-Idade , Otite Média com Derrame/complicações , Otite Média com Derrame/imunologia , Resultado do Tratamento
12.
Allergy ; 73(11): 2192-2204, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29672862

RESUMO

BACKGROUND: Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium-derived thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma. METHODS: Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression, and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles (DEP) to determine AhR-mediated IL-33, Il-25, and TSLP synthesis and release. RESULTS: Primary bronchial epithelial cells exposed to DEP showed upregulation of IL-33, IL-25, and TSLP. These effects were abolished by knockdown of AhR by siRNA. Increased AhR/ARNT binding to promoters of IL-33, IL-25, and TSLP was found using chromatin immunoprecipitation (ChIP) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL-33, IL-25, and TSLP. These patients derived clinical benefit from anti-IgE treatment. CONCLUSION: Aryl hydrocarbon receptor activation by DEP mediates upregulation of IL-33, IL-25, and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma.


Assuntos
Asma/etiologia , Asma/metabolismo , Citocinas/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Emissões de Veículos , Alérgenos/imunologia , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Asma/diagnóstico , Asma/terapia , Biópsia , Citocinas/genética , Feminino , Imunofluorescência , Regulação da Expressão Gênica , Humanos , Imunoglobulina E/imunologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Transporte Proteico , Testes de Função Respiratória , Mucosa Respiratória/patologia , Células Th2/imunologia , Células Th2/metabolismo
13.
Cochrane Database Syst Rev ; 3: CD010288, 2018 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-29551015

RESUMO

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.


Assuntos
Antialérgicos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Fibrose Cística/complicações , Omalizumab/uso terapêutico , Antialérgicos/efeitos adversos , Anticorpos Anti-Idiotípicos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antifúngicos/uso terapêutico , Aspergilose Broncopulmonar Alérgica/etiologia , Término Precoce de Ensaios Clínicos , Humanos , Itraconazol/uso terapêutico , Omalizumab/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Biochem Biophys Res Commun ; 498(4): 996-1001, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29550477

RESUMO

Antibody formation against therapeutic agents, such as tumor necrosis factor inhibitors and Factor VIII, that leads to treatment failure has become a major challenge in the treatment of rheumatoid arthritis and hemophilia. It is well known that anti-CD154 antibodies have the highest potential to inhibit these types of adverse immune responses. Nevertheless, the formation of thromboemboli is the major hurdle in the clinical application of these anti-CD154 blocking antibodies. For this, we attempted to derive an idea as to how this major complication can be eliminated. Consequently, we developed a novel anti-CD154 chimeric antibody, which was made by genetic modification of a portion of human IgG4 Fc. This antibody has an almost comparable antigen binding affinity to a previously developed 5C8 clone and near completely inhibited CD40-CD154 interaction and T cell-dependent B cell activation in vitro. Even under the condition, where we injected immune complexes comprised of RD-05 and CD154 antigen, the formation of thromboembolism was not seen in human FcγRIIA-transgenic mice, whereas the converse was exactly true in the case of 5C8 antibody. Notably, just two injections of RD-05 antibody was sufficient to inhibit the antibody formation against adalimumab during 3-4 months in cynomolgus macaques, in which adalimumab was repeatedly injected for 12 weeks. Based on these findings, we suggest that this RD-05 antibody can be applied to antibody-mediated autoimmune diseases, including systemic lupus erythematosus and immune thrombocytopenic purpura.


Assuntos
Anticorpos Anti-Idiotípicos/farmacologia , Formação de Anticorpos/efeitos dos fármacos , Doenças Autoimunes/tratamento farmacológico , Ligante de CD40/imunologia , Trombose/etiologia , Adalimumab/imunologia , Animais , Anticorpos Anti-Idiotípicos/uso terapêutico , Doenças Autoimunes/imunologia , Fator VIII/imunologia , Humanos , Macaca , Camundongos , Camundongos Transgênicos
15.
Curr Opin Allergy Clin Immunol ; 18(3): 184-189, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29601354

RESUMO

PURPOSE OF REVIEW: Target therapy is the necessary step towards personalized medicine. The definition of asthma phenotypes and underlying mechanisms (endotypes) represent a key point in the development of new asthma treatments. Big data analysis, biomarker research and the availability of monoclonal antibodies, targeting specific cytokines is leading to the rapid evolution of knowledge. In this review, we sought to outline many of the recent advances in the field. RECENT FINDINGS: Several attempts have been made to identify asthma phenotypes, sometimes with contrasting results. More success has been obtained concerning the pathogenetic mechanism of specific asthma patterns with the consequent identification of biomarkers and development of effective ad hoc treatment. SUMMARY: We are in the middle of an extraordinary revolution of our mode of thinking about and approaching asthma. All the effort in the identification of clusters of patients with different disease clinical patterns, prognosis and response to treatment is closely linked to the identification of endotypes (Th2-low and Th2-high). This approach has allowed the development of the specific treatments (anti IgE, Anti IL5 and IL5R) that are now available and is leading to new ones.


Assuntos
Antiasmáticos/uso terapêutico , Asma/terapia , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Medicina de Precisão/métodos , Células Th2/imunologia , Antiasmáticos/farmacologia , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Asma/genética , Asma/imunologia , Biomarcadores/análise , Humanos , Fatores Imunológicos/farmacologia , Interleucinas/análise , Interleucinas/antagonistas & inibidores , Interleucinas/imunologia , Terapia de Alvo Molecular/métodos , Seleção de Pacientes , Fenótipo , Prognóstico , Índice de Gravidade de Doença , Escarro/imunologia , Células Th2/metabolismo , Resultado do Tratamento
16.
BMC Pediatr ; 18(1): 73, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29466963

RESUMO

BACKGROUND: The primary goal of asthma management is to achieve disease control for reducing the risk of future exacerbations and progressive loss of lung function. Asthma not responding to treatment may result in significant morbidity. In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong or adherence to treatment may be poor. It is then crucial to distinguish these cases from the truly "severe therapy-resistant" asthmatics by a proper filtering process. Herein we report on four cases diagnosed as difficult asthma, detail the workup that resulted in the ultimate diagnosis, and provide the process that led to the prescription of omalizumab. CASE PRESENTATION: All children had been initially referred because of asthma not responding to long-term treatment with high-dose inhaled steroids, long-acting ß2-agonists and leukotriene receptor antagonists. Definitive diagnosis was severe asthma. Three out four patients were treated with omalizumab, which improved asthma control and patients' quality of life. We reviewed the current literature on the diagnostic approach to the disease and on the comorbidities associated with difficult asthma and presented the perspectives on omalizumab treatment in children and adolescents. Based on the evidence from the literature review, we also proposed an algorithm for the diagnosis of pediatric difficult-to-treat and severe asthma. CONCLUSIONS: The management of asthma is becoming much more patient-specific, as more and more is learned about the biology behind the development and progression of asthma. The addition of omalizumab, the first targeted biological treatment approved for asthma, has led to renewed optimism in the management of children and adolescents with atopic severe asthma.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Asma/tratamento farmacológico , Omalizumab/uso terapêutico , Asma/diagnóstico , Criança , Pré-Escolar , Humanos , Masculino , Índice de Gravidade de Doença
17.
Intern Emerg Med ; 13(2): 155-176, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29238905

RESUMO

Asthma is a chronic inflammatory multifactorial disorder of the airways characterized by the involvement of immune cells and mediators in its onset and maintenance. Traditional therapeutic strategies have been unsatisfactory in controlling the underlying pathology, especially in the more severe states. Hence in the last couple of decades, new biological approaches targeting molecular mediators have been developed. In this narrative review we examine biological agents currently available for the management of severe asthma, focusing our attention on their clinical application, pros and cons, and in particular on gaps regarding the use of these agents. The most well-known and used biologic agent in clinical practice is omalizumab, though there is emerging evidence for mepolizumab too. The future of these biological therapies is to broaden our knowledge of their practical use and ascertain predictive biomarkers, or define an algorithm, useful in the optimal application of these 'biological weapons'.


Assuntos
Asma/tratamento farmacológico , Fatores Biológicos/farmacologia , Fatores Biológicos/farmacocinética , Antiasmáticos/farmacocinética , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores Biológicos/uso terapêutico , Humanos , Interleucina-5/antagonistas & inibidores , Interleucina-5/farmacologia , Interleucina-5/uso terapêutico , Omalizumab/farmacocinética , Omalizumab/farmacologia , Omalizumab/uso terapêutico
19.
Curr Opin Pulm Med ; 24(1): 4-10, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29036018

RESUMO

PURPOSE OF REVIEW: Asthma is a heterogeneous disease consisting of different phenotypes that are driven by different mechanistic pathways. The purpose of this review is to emphasize the important role of precision medicine in asthma management. RECENT FINDINGS: Despite asthma heterogeneity, the approach to management has been on the basis of disease severity, with the most severe patients reserved for the maximum treatments with corticosteroids and bronchodilators. At the severe end, the recent availability of biologic therapies in the form of anti-IgE (omalizumab) and anti-IL5 therapies (mepolizumab and reslizumab) has driven the adaptation of precision medicine. These therapies are reserved for severe asthma with defined either allergic or eosinophilic background, respectively. SUMMARY: Unbiased definition of phenotypes or endotypes (which are phenotypes defined by mechanisms) is an important step towards the use of precision medicine in asthma. Although T2-high asthma has been defined with targets becoming available for treating allergic or eosinophilic asthma, the definition of non-T2 phenotypes remains a priority. Precision medicine is also dependent on the definition of biomarkers that can help differentiate between these phenotypes and pinpoint patients suitable for specific-targeted therapies. Thus, precision medicine links phenotypes (endotypes) to targeted treatments for better outcomes.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/fisiopatologia , Terapia de Alvo Molecular , Fenótipo , Medicina de Precisão , Anticorpos Anti-Idiotípicos/uso terapêutico , Asma/genética , Biomarcadores/análise , Humanos , Índice de Gravidade de Doença
20.
Clin Rev Allergy Immunol ; 54(1): 88-101, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28748365

RESUMO

Urticaria is a common, mast cell-driven disease presenting with wheals or angioedema or both. In the last years, urticaria has increasingly attracted notice to clinicians and researchers, last but not least inspired by the approval of omalizumab, an anti-IgE antibody, for urticaria treatment. There is wide consensus on the clinical classification based on duration and elicitation. However, the pathogenesis is incompletely understood. This review summarizes current guidelines for the management and novel insights in the pathogenesis of urticaria with special focus on their impact on clinical praxis. The classification of urticaria subgroups is mainly based on clinical criteria: acute and chronic urticaria (CU). Chronic urticaria comprises both chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU) that includes physical and non-physical urticarias. Recent research focused on characterizing the role of cells and mediators involved in the pathogenesis of urticaria, identifying the mechanisms of mast cell activation, and investigating underlying autoimmune processes in chronic spontaneous urticarial. Currently, non-sedating antihistamines and omalizumab, an antiimmunoglobulin E antibody, are recommended for the therapy of chronic urticaria, as both exhibit a favorable efficacy and safety profile. Novel therapeutic strategies aim at specifically targeting cells and mediators involved in the pathogenesis of urticaria.


Assuntos
Angioedema/terapia , Antialérgicos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Mastócitos/imunologia , Urticária/terapia , Angioedema/imunologia , Doença Crônica , Humanos , Omalizumab/uso terapêutico , Urticária/imunologia
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