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1.
J Allergy Clin Immunol Pract ; 5(1): 23-31, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28065340

RESUMO

Sublingual immunotherapy (SLIT) relies on high doses of allergens to treat patients with type I allergies. Although SLIT is commonly performed without any adjuvant or delivery system, allergen(s) could be further formulated with allergen-presentation platforms to better target oral dendritic cells eliciting regulatory immune responses. Improving the availability of allergens to the immune system should enhance SLIT efficacy, while allowing to decrease allergen dosing. Herein, we present an overview of adjuvants and vector systems that have been, or could be, considered as candidate allergen-presentation platforms for the sublingual route. Such platforms encompass adjuvants capable of stimulating allergen-specific TH1 and/or regulatory CD4+ T-cell responses, including 1,25-dihydroxy vitamin D3, glucocorticoids, Toll-like receptor ligands as well as selected bacterial probiotic strains. A limiting factor for SLIT efficacy is the number of dendritic cells capturing the allergens in the upper layers of oral tissues. Thus, adsorption or encapsulation of the allergen(s) within mucoadhesive particulate vector (or delivery) systems also has the potential to significantly enhance SLIT efficacy due to a facilitated allergen uptake by tolerogenic oral dendritic cells.


Assuntos
Alérgenos/uso terapêutico , Células Dendríticas/imunologia , Mucosa Bucal/imunologia , Boca/imunologia , Imunoterapia Sublingual/métodos , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Alérgenos/imunologia , Animais , Apresentação de Antígeno , Colecalciferol/análogos & derivados , Colecalciferol/imunologia , Glucocorticoides/imunologia , Humanos , Probióticos/metabolismo , Imunoterapia Sublingual/tendências , Receptores Toll-Like/metabolismo
2.
Mucosal Immunol ; 10(3): 695-704, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27731323

RESUMO

The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4+ T cells with a suppressive activity. Furthermore, C1q expression is upregulated in peripheral blood mononuclear cells of allergic patients in the course of successful allergen immunotherapy. Herein, we investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin (OVA) or birch pollen (BP)-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness (AHR), eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs. Administration of C1q does not expand IL-10+/Foxp3+ regulatory T cells in the lungs, spleen, or in the blood. Depletion of plasmacytoid dendritic cells (pDCs) abrogates the capacity of C1q to reduce AHR and eosinophilic infiltrates in OVA-sensitized mice. Also C1q treatment inhibits the activation of human and mouse pDCs by CpGs, thereby demonstrating a critical role for pDCs in the anti-inflammatory activity of C1q. We conclude that regulatory dendritic cells can mediate a potent direct anti-inflammatory activity via the expression and/or secretion of molecules such as C1q, independently of their capacity to expand the pool of regulatory T cells.


Assuntos
Complemento C1q/metabolismo , Células Dendríticas/imunologia , Eosinófilos/imunologia , Hipersensibilidade/imunologia , Pulmão/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Alérgenos/imunologia , Animais , Betula , Células Cultivadas , Complemento C1q/administração & dosagem , Feminino , Humanos , Interleucina-10/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Extratos Vegetais , Pólen/imunologia
3.
Allergy ; 71(2): 220-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26485347

RESUMO

BACKGROUND: Understanding patterns of IgE sensitization in Dermatophagoides-allergic patients living in various geographical areas is necessary to design a product suitable for worldwide allergen immunotherapy (AIT). METHODS: Using a HIFI Allergy customized microarray assay, IgEs specific for 12 purified allergens from Dermatophagoides pteronyssinus or D. farinae were assessed in sera from 1302 house dust mite (HDM)-allergic patients living in various areas. Comprehensive mass spectrometric (MS) analyses were conducted to characterize HDM extracts, as well as purified bodies and feces. RESULTS: Patterns of IgE reactivity to HDM allergens are comparable in all cohorts of patients analyzed, encompassing adults and 5- to 17-year-old children, as well as American, Canadian, European, and Japanese patients. Overall, >70% and >80% of HDM-allergic patients are sensitized to group 1 and group 2 allergens, respectively, from D. pteronyssinus and/or D. farinae species. Furthermore, 20-47% of patients also have IgEs to allergens from groups 4, 5, 7, 13, 15, 21, and 23. All patients have IgEs to allergens present in mite bodies and feces. MS-based analyses confirmed the presence of mite allergens recorded by IUIS in D. pteronyssinus and D. farinae extracts, with groups 2, 8, 10, 11, 14, and 20 prominent in bodies and groups 1, 6, 18, and 23 well represented in feces. CONCLUSIONS: Mite-specific AIT should rely upon a mixture of D. pteronyssinus and D. farinae extracts, manufactured from both feces and bodies. Such a combination is appropriate to treat children and adult Dermatophagoides-allergic patients from Asia, Europe, and North America.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Pyroglyphidae/imunologia , Adolescente , Adulto , Alérgenos/isolamento & purificação , Animais , Especificidade de Anticorpos , Antígenos de Dermatophagoides/isolamento & purificação , Criança , Pré-Escolar , Dessensibilização Imunológica , Europa (Continente) , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Imunização , Imunoglobulina E/sangue , Masculino , Adulto Jovem
4.
Allergy ; 70(4): 408-19, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25631199

RESUMO

BACKGROUND: A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. METHODS: Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). RESULTS: Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207+ Langerhans cells (LCs) and CD11c+ myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68+ macrophages, CD117+ mast cells, and CD4+ /CD8+ T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207+ LCs found in oral tissues from patients with OAS, when compared to OAS- patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE+ cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68+ macrophages located in the LP, and to a lesser extent CD207+ LCs in the epithelium. CONCLUSION: Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207+ LCs possibly involved in the physiopathology of OAS and (ii) CD68+ macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT.


Assuntos
Alérgenos/imunologia , Células Apresentadoras de Antígenos/imunologia , Betula , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos de Superfície/metabolismo , Biomarcadores , Biópsia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Gengiva/imunologia , Gengiva/metabolismo , Gengiva/patologia , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Imunofenotipagem , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Síndrome , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
5.
Clin Exp Allergy ; 43(12): 1362-73, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24261946

RESUMO

BACKGROUND: During allergen-specific sublingual immunotherapy (SLIT), the relevance of changes in specific IgE and IgG antibody titres to treatment efficacy remains to be evaluated at an individual patient level. OBJECTIVE: To investigate whether antibody responses can be used as biomarkers for SLIT efficacy. METHODS: Comprehensive quantitative, qualitative and functional analyses of allergen-specific IgA, IgE, IgG1-4 and IgM responses were performed using purified Phl p 1 to 12 allergens in sera, saliva and nasal secretions from 82 grass pollen allergic patients. These patients were enrolled in a randomized, double-blind placebo-controlled study and assessed in an allergen challenge chamber (ClinicalTrials.gov NCT00619827). Antibody responses were monitored in parallel to clinical responses before and after daily sublingual treatment for 4 months with either a grass pollen or a placebo tablet. RESULTS: A significant mean improvement (i.e. 33-40.6%) in rhinoconjunctivitis total symptom scores was observed in SLIT recipients, irrespective of their baseline patterns of IgE sensitization (i.e. narrow, intermediate, broad) to grass pollen allergens. SLIT did not induce any de novo IgE sensitization. Clinical responders encompassed both immunoreactive patients who exhibited strong increases in titres, affinity and/or blocking activity of grass-pollen-specific IgGs (representing 17% of treated patients), as well as patients with no detectable antibody responses distinguishing them from the placebo group. No significant changes were detected in antibody titres in saliva and nasal washes, even in clinical responders. CONCLUSIONS AND CLINICAL RELEVANCE: Sublingual immunotherapy with a grass pollen tablet is efficacious irrespective of the patients' baseline sensitization to either single or multiple grass pollen allergens. Seric IgG responses may contribute to SLIT-induced clinical tolerance in a fraction (i.e. 17%) of patients, but additional immune mechanisms are involved in most patients. Consequently, antibody responses cannot be used as a marker of SLIT efficacy at an individual patient level.


Assuntos
Alérgenos/imunologia , Poaceae/efeitos adversos , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Alérgenos/administração & dosagem , Anticorpos/sangue , Anticorpos/imunologia , Anticorpos/metabolismo , Humanos , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Rinite Alérgica Sazonal/metabolismo , Resultado do Tratamento
6.
Clin Exp Allergy ; 42(12): 1745-55, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23181790

RESUMO

BACKGROUND: Surrogate biomarkers of efficacy are needed in support of allergen-specific immunotherapy. OBJECTIVE: The aim of this study was to relate changes in peripheral CD4(+) T cell responses to clinical efficacy during sublingual immunotherapy (SLIT). METHODS: Allergen-specific CD4(+) T cell responses were assessed in peripheral blood mononuclear cells (PBMCs) from 89 grass pollen-allergic individuals enrolled in a double-blind placebo-controlled SLIT study conducted in an allergen exposure chamber (ClinicalTrials.gov NCT00619827). Surface phenotype, proliferative responses, cytokine production and gene expression were analysed in coded samples at baseline, and after 2 and 4 months of SLIT, in PBMCs after in vitro allergen stimulation or among MHC class II/peptide (pMHCII)-tetramer-positive CD4(+) T cells. RESULTS: SLIT induced a 29.3% improvement of the average rhinoconjunctivitis total symptom score in the active group, when compared to the placebo group. In parallel, only minor changes in proportions of CD4(+) T cells expressing Th1 (CCR5(+), CXCR3(+)), Th2 (CRTh2(+), CCR4(+)) and Treg (CD25(+), CD127(-), Foxp3(+)) markers were detected. A down-regulation of IL-4 and IL-10 gene expression and IL-10 secretion (P < 0.001) were observed, as well as a decrease in the frequency of potential "pro-allergic" CD27(-) Th2 cells from patients receiving active tablets (P < 0.001), but without any correlation with clinical benefit. pMHCII-tetramer analyses failed to document any major impact in both numbers and polarization of circulating Phl p 1- and Phl p 5-specific CD4(+) T cells, confirming that early clinical improvement during SLIT is not associated with dramatic alterations in T lymphocyte responses. CONCLUSION & CLINICAL RELEVANCE: Changes in patterns of peripheral CD4(+) T cells are not markers for the early onset of efficacy during SLIT.


Assuntos
Alérgenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Conjuntivite Alérgica/terapia , Dessensibilização Imunológica/métodos , Proteínas de Plantas/imunologia , Poaceae/imunologia , Rinite Alérgica Sazonal/terapia , Administração Sublingual , Alérgenos/administração & dosagem , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Conjuntivite Alérgica/imunologia , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Humanos , Ativação Linfocitária , Masculino , Proteínas de Plantas/administração & dosagem , Pólen/imunologia , Valor Preditivo dos Testes , Rinite Alérgica Sazonal/imunologia , Resultado do Tratamento
7.
Clin Exp Allergy ; 42(10): 1510-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22994348

RESUMO

BACKGROUND: The impact of sublingual immunotherapy (SLIT) on IgE neosensitization remains to be evaluated in large cohorts of patients. OBJECTIVES: The aim of this study was to assess the dynamics of antibody responses induced in patients with allergic rhinitis during a 12-month treatment with sublingual tablets of house dust mites (HDM) allergen extracts. METHODS: Antibody responses were assessed in relationship with neosensitization and clinical benefit in sera from 509 European house dust mite-allergic patients before and after 1 year of daily sublingual immunotherapy, using tablets containing Dermatophagoides pteronyssinus plus D farinae extracts or placebo (ClinicalTrials.gov NCT00674700). Patients were followed for one additional year after treatment cessation. IgE and IgG4 antibodies specific for mite extracts or purified group 1, 2 and 10 allergens were assessed using Immulite, Immunocap and ISAC assays. RESULTS: After 1 year of SLIT, mite-specific IgE and IgG4 titres increased by 1.5-fold and fourfold, respectively, in the active, but not in the placebo group. A strong IgG4 induction occurred in a subgroup (i.e. 10-15%) of "immunoreactive" patients, without any correlation with improvement in the average adjusted symptom score. Pre-existing IgE levels to purified mite allergens were not impacted during immunotherapy, and no de novo IgE responses to group 1, 2, 10 allergens were induced in patients who were unsensitized prior to immunotherapy. Similarly, no IgE neosensitization to wheat germ or yeast components used in the mite culture medium was observed. CONCLUSIONS AND CLINICAL RELEVANCE: We document in a cohort of 509 patients followed over a 2-year period that SLIT does not induce any IgE neosensitization to allergens contained in the vaccine, such as groups 1, 2 as well as the food-related group 10 allergen. This observation further corroborates the safer safety profile of SLIT over SCIT.


Assuntos
Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica/métodos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Administração Sublingual , Adolescente , Adulto , Animais , Antígenos de Dermatophagoides/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pyroglyphidae/imunologia , Rinite Alérgica Perene/terapia , Comprimidos/administração & dosagem , Resultado do Tratamento , Adulto Jovem
8.
Clin Exp Allergy ; 41(12): 1784-92, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22092967

RESUMO

BACKGROUND: Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes. OBJECTIVE: To develop a chronic house dust mite (HDM) allergy model to evaluate sublingual therapeutic vaccine candidates. METHODS: The BABL/c mice that were used were sensitized with Dermatophagoides pteronyssinus (Dpte) and Dermatophagoides farinae (Dfar) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy (SLIT) with either Dpte, Dfar or Dpte/Dfar extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho-alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively. RESULTS: Mice sensitized to Dpte and Dfar allergens exhibited strong airway hyperresponsiveness (AHR) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted Th2-biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts-based vaccines. In this model, SLIT decreased AHR and Th2 responses and induced HDM-specific IgAs in saliva. The Dpte/Dfar mix proved the most efficacious when compared to Dpte or Dfar extracts alone. CONCLUSIONS AND CLINICAL RELEVANCE: The efficacy of a sublingual vaccine based on a Dpte/Dfar allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation animal model is a useful tool to design and select candidate vaccines to be tested in humans.


Assuntos
Antígenos de Dermatophagoides/imunologia , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/terapia , Dessensibilização Imunológica , Pyroglyphidae/imunologia , Administração Sublingual , Animais , Antígenos de Dermatophagoides/administração & dosagem , Hiper-Reatividade Brônquica/prevenção & controle , Linfócitos T CD4-Positivos/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/imunologia , Inflamação/terapia , Camundongos , Camundongos Endogâmicos BALB C , Células Th2/imunologia , Vacinas/imunologia
9.
Allergy ; 66(12): 1530-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21883279

RESUMO

BACKGROUND: Biomarkers predicting the safety and efficacy of sublingual immunotherapy (SLIT) remain to be established. METHODS: Eighty-nine patients with allergic rhinoconjunctivitis to grass pollen received either a placebo or five-grass-pollen daily tablet sublingually for 4 months. Following exposure in an allergen challenge chamber, clinical responders and nonresponders were identified individually by evaluating their rhinoconjunctivitis total symptom score (RTSS). Activation of peripheral blood basophils was measured by cytofluorometry before and after 2 or 4 months of immunotherapy, based on CD203c surface expression following allergen stimulation. RESULTS: Patients receiving the grass-pollen tablet had a relative mean improvement of 29.3% vs placebo in the average RTSS after 4 months of SLIT (P < 0.0003). No significant changes in basophil activation were noticed after 2 or 4 months of SLIT despite induction of specific IgGs. Among individual clinical responders, basophil activation was either decreased, increased, or unmodified during SLIT. Levels of basophil activation prior to immunotherapy were not predictive of local adverse reactions associated with immunotherapy. A moderate association was found between basophil activation and allergen-specific IgE levels, skin reactivity, or RTSS, suggesting that the former is, to some extent, indicative of disease severity. As such, patients with the highest level of basophil activation before treatment were more likely to benefit clinically from SLIT. CONCLUSIONS: Allergen reactivity of peripheral blood basophils is not a biomarker for adverse events or early onset of clinical responses to SLIT.


Assuntos
Alérgenos/imunologia , Basófilos/imunologia , Dessensibilização Imunológica , Poaceae/imunologia , Pólen/imunologia , Administração Sublingual , Alérgenos/administração & dosagem , Especificidade de Anticorpos , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/terapia , Dessensibilização Imunológica/efeitos adversos , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Testes Cutâneos , Resultado do Tratamento
10.
Clin Exp Allergy ; 41(6): 821-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21418343

RESUMO

BACKGROUND: Major histocompatibility complex (MHC) class II tetramers (tetramers) allow to detect allergen-specific CD4(+) T cells at a single-cell level. Limits to this technology include HLA restriction and the need to identify immunodominant T cell epitopes. OBJECTIVE: Assessing the expression of various activation markers following allergen stimulation to replace tetramer staining. METHODS: Peripheral blood mononuclear cells (PBMCs) from 25 birch pollen, grass pollen or house dust mite allergic individuals were stimulated with peptide mixes encompassing immunodominant epitopes from corresponding major allergens. After 2 weeks of in vitro amplification, cells were stained with both the appropriate tetramer and antibodies directed to CD25, CD30, CD39, CD69, CD137, CD154, GITR, HLA-DR and ICOS, before FACS analysis. RESULTS: Following allergen stimulation, percentages of tetramer(+) cells among CD4(+) CD154(+) cells range from 5% to 87%, depending upon donors. As for CD154, a large inter-individual variability is observed in terms of surface expression for all activation markers tested in allergen-stimulated PBMCs. T cells reactive with either tetramers (0.4-10.4% CD4(+) T cells) or anti-marker antibodies (2.2-32.7% CD4(+) T cells), but not both, are observed, reflecting the presence of anergic as well as non-specifically activated cells. Tetramer(+) /marker(+) , tetramer(+) /marker(-) and tetramer(-) /marker(+) cells were compared for their capacity to express cytokines, demonstrating that only the former represent bona fide allergen-specific activated CD4(+) T cells, based upon a higher expression of cytokines or corresponding genes in presence of the allergen. CONCLUSION AND CLINICAL RELEVANCE: No strict correlation exists between tetramer staining and the expression of multiple activation markers in stimulated CD4(+) T cells. Dual staining allows to discriminate functional tetramer(+) /marker(+) vs. anergic (tetramer(+) /marker(-) ) allergen-specific T cells or non-specifically activated (tetramer(-) /marker(+) ) T cells. Combining tetramer staining with the detection of activation markers helps understanding patient heterogeneity regarding specific CD4(+) T cell responses. This approach has immediate relevance for monitoring immune changes induced during specific immunotherapy.


Assuntos
Alérgenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe II/imunologia , Ligante de CD40/imunologia , Citocinas/genética , Citocinas/imunologia , Epitopos/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Rinite Alérgica Perene/imunologia
11.
Clin Exp Allergy ; 40(3): 505-19, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19895591

RESUMO

BACKGROUND: Differences between major allergens from distinct grass species remain to be investigated, both in terms of structure and antigenicity. METHODS: Group 1 and 5 allergens purified from five common Pooideae species were analysed by mass spectrometry (MS). Major histocompatibility complex (MHC) class II-restricted T cell epitopes were identified using predictive algorithms and human leucocyte antigen (HLA)-binding assays. CD4+ T cell reactivity and IgE binding were assessed based on the induction of CD154 expression in peripheral blood mononuclear cells and using competitive ELISA assays, respectively. RESULTS: MS analysis of group 5 pollen allergens reveals considerable intra- and inter-species variability in amino acid sequence, with 30-50 predominant isoforms found for each species. Differences in the amino acid sequence as well as N- and O-glycosylation contribute to the variability of group 1 allergens, yielding 5-10 main isoforms, depending on the species. Out of 14 MHC class II-restricted T cell epitopes identified within group 1, only one is conserved among the five grass species. Significant differences in binding affinities for HLA-DR molecules result in variable CD4+ T cell recognition of group 1 and 5 allergens purified from the various species. Up to 38% and 85% of patients exhibit seric IgE responses to species-restricted (or semi-restricted) epitopes associated with group 1 or 5 allergens, respectively. CONCLUSION: Major pollen allergens from distinct grass species bear both shared and species-restricted T and B cell immune epitopes. When compared with single extracts, a five grass pollen extract is thus more suitable for specific immunotherapy, as it contains a broader repertoire of the IgE epitopes to which patients are sensitized.


Assuntos
Alérgenos/química , Alérgenos/classificação , Dessensibilização Imunológica , Poaceae/química , Poaceae/classificação , Pólen/química , Alérgenos/imunologia , Alérgenos/isolamento & purificação , Sequência de Aminoácidos , Animais , Reações Antígeno-Anticorpo , Epitopos/química , Epitopos/imunologia , Humanos , Imunoglobulina E/imunologia , Leucócitos/imunologia , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mapeamento de Peptídeos , Conformação Proteica , Especificidade da Espécie , Linfócitos T/imunologia
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