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1.
Clin Exp Allergy ; 54(2): 120-129, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37990117

RESUMEN

BACKGROUND: Local application site reactions are common with sublingual allergy immunotherapy (AIT)-tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT-tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT-tablets compared with the sublingual route in adult subjects with AR/C. METHODS: Adults (n = 164) aged 18-65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment-related adverse events (TRAEs) during the first 28 days of treatment. RESULTS: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p = .16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p = .01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%). CONCLUSION: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT-tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT-tablets for AR/C.


Asunto(s)
Conjuntivitis Alérgica , Rinitis Alérgica Estacional , Rinitis Alérgica , Inmunoterapia Sublingual , Adulto , Humanos , Proyectos Piloto , Rinitis Alérgica Estacional/terapia , Administración Sublingual , Resultado del Tratamiento , Rinitis Alérgica/terapia , Inmunoterapia Sublingual/efectos adversos , Comprimidos , Alérgenos
2.
Artículo en Inglés | MEDLINE | ID: mdl-38441370

RESUMEN

BACKGROUND: Chronic spontaneous urticaria (CSU) is both physically and emotionally stressful, and guideline recommendations are often not optimally implemented in clinical practice. The objective of this study was to provide an overview on the patient journey in CSU and to develop a mathematical model based on solid data. METHODS: The journey of CSU patients in Germany was traced through literature review and expert meetings that included medical experts, pharmacists and representatives of patient organizations. The current situation's main challenges in the patient journey (education, collaboration and disease management) were discussed in depth. Then, a probabilistic model was developed in a co-creation approach to simulate the impact of three potential improvement strategies: (1) patient education campaign, (2) medical professional education programme and (3) implementation of a disease management programme (DMP). RESULTS: Chronic spontaneous urticaria patients are severely burdened by delays in diagnosis and optimal medical care. Our simulation indicates that in Germany, it takes on average of 3.8 years for patients to achieve disease control in Germany. Modelling all three optimization strategies resulted in a reduction to 2.5 years until CSU symptom control. On a population level, the proportion of CSU patients with disease control increased from 44.2% to 58.1%. CONCLUSION: In principle, effective CSU medications and a disease-specific guideline are available. However, implementation of recommendations is lagging in practice. The approach of quantitative modelling of the patient journey validates obstacles and shows a clear effect of multiple interventions on the patient journey. The data generated by our simulation can be used to identify strategies for improving patient care. Our approach might helping in understanding and improving the management of patients beyond CSU.

3.
Allergy ; 78(3): 639-662, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36587287

RESUMEN

The current monkeypox disease (MPX) outbreak constitutes a new threat and challenge for our society. With more than 55,000 confirmed cases in 103 countries, World Health Organization declared the ongoing MPX outbreak a Public Health Emergency of International Concern (PHEIC) on July 23, 2022. The current MPX outbreak is the largest, most widespread, and most serious since the diagnosis of the first case of MPX in 1970 in the Democratic Republic of the Congo (DRC), a country where MPX is an endemic disease. Throughout history, there have only been sporadic and self-limiting outbreaks of MPX outside Africa, with a total of 58 cases described from 2003 to 2021. This figure contrasts with the current outbreak of 2022, in which more than 55,000 cases have been confirmed in just 4 months. MPX is, in most cases, self-limiting; however, severe clinical manifestations and complications have been reported. Complications are usually related to the extent of virus exposure and patient health status, generally affecting children, pregnant women, and immunocompromised patients. The expansive nature of the current outbreak leaves many questions that the scientific community should investigate and answer in order to understand this phenomenon better and prevent new threats in the future. In this review, 50 questions regarding monkeypox virus (MPXV) and the current MPX outbreak were answered in order to provide the most updated scientific information and to explore the potential causes and consequences of this new health threat.


Asunto(s)
Monkeypox virus , Mpox , Niño , Femenino , Humanos , Embarazo , Brotes de Enfermedades , Mpox/diagnóstico , Mpox/epidemiología
4.
J Allergy Clin Immunol ; 149(4): 1185-1194, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35090948

RESUMEN

Fascinating immunologic mechanisms that are crucial for pregnancy can, however, lead to the development of different skin conditions, of which atopic dermatitis (AD) is the most frequent one. AD in pregnancy may occur de novo or as a recurrence or exacerbation of known chronic AD. The changes in hormone levels that occur during pregnancy influence the cytokine balance and can lead to manifestation of eczematous lesions, currently classified as atopic eruption of pregnancy. The diagnosis of atopic eruption of pregnancy may be challenging, especially in patients who developed this skin disease de novo during gestation. The treatment is another challenge, because it needs to be safe for both the mother and especially the unborn child. Emollients make up the basis of the therapy. Topical corticosteroids and calcineurin inhibitors are also safe treatment options, and ultraviolet therapy can be added, if required. Use of cyclosporin A is possible for systemic therapy during pregnancy, whereas safety data on new drugs such as biologics approved for AD are limited to small case series. This review is aimed at summarizing available data on the mechanisms that lead to AD during gestation, differential diagnostic evaluations, and treatment options.


Asunto(s)
Dermatitis Atópica , Fármacos Dermatológicos , Eccema , Inhibidores de la Calcineurina/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/terapia , Fármacos Dermatológicos/uso terapéutico , Emolientes/uso terapéutico , Femenino , Humanos , Embarazo
5.
Exp Dermatol ; 30(11): 1699-1704, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33751678

RESUMEN

Herpes simplex virus type 1 (HSV-1) can induce in certain individuals with atopic dermatitis (AD) severe cutaneous infections that can spread throughout the entire body, a condition named as AD complicated by eczema herpeticum (ADEH). It has been recently found that ADEH patients can produce specific IgE against HSV-1 proteins, which may contribute to lower protection against HSV-1. However, little is known about the capacity of these HSV-1 proteins to produce an inflammatory response at the skin level. In this study, using a mouse model of AD-like dermatitis, three HSV-1 proteins (glycoprotein D -gD-, glycoprotein B -gB- and VP22) were applied on tape-stripped back skin mice in three exposures periods. Ovalbumin (OVA) and 0.9% NaCl were used as positive and negative controls, respectively. Skin samples were obtained for analysis of specific cell components of skin infiltration. The results showed that the viral protein gD induced a statistically significant increase in the number of dermal infiltrating CD3+, CD4+ cells and mast cells compared with the negative control group. gD was also able to induce epidermal thickening and epidermal infiltration of T cells closely related to the one produced in mice sensitized with OVA. However, VP22 and gB contributed to a lesser extent to skin inflammation. These results showed that proteins from HSV-1, especially gD, can have per se an important T cell and mast cell-driven inflammatory potential at the skin level.


Asunto(s)
Dermatitis Atópica/virología , Dermatitis/virología , Herpesvirus Humano 1 , Proteínas Virales , Animales , Modelos Animales de Enfermedad , Ratones
6.
Allergy ; 76(11): 3307-3313, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33657648

RESUMEN

Following the emergency use authorization of the mRNA-1273 vaccine on the 18th of December 2020, two mRNA vaccines are in current use for the prevention of coronavirus disease 2019 (COVID-19). For both mRNA vaccines, the phase III pivotal trials excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and the United States, anaphylactic reactions were reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000)-contained in both vaccines as the PEG-micellar carrier system-as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEGylated lipids can be IgE-mediated, but may also result from complement activation-related pseudoallergy (CARPA) that has been described in similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such as gadolinium-based contrast media. Skin prick, intradermal and epicutaneous tests, in vitro sIgE assessment, evaluation of sIgG/IgM, and basophil activation tests are being used to demonstrate allergic reactions to various components of the vaccines.


Asunto(s)
Anafilaxia , COVID-19 , Vacuna nCoV-2019 mRNA-1273 , Alérgenos , Anafilaxia/etiología , Vacunas contra la COVID-19 , Activación de Complemento , Humanos , Inmunoglobulina G , Polietilenglicoles/efectos adversos , SARS-CoV-2 , Estados Unidos
7.
Allergy ; 76(4): 1041-1052, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32869882

RESUMEN

The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.


Asunto(s)
Hipersensibilidad , Medicina de Precisión , Alérgenos , Desensibilización Inmunológica , Genómica , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/terapia
8.
J Allergy Clin Immunol ; 145(4): 1208-1218, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31707051

RESUMEN

BACKGROUND: Fifteen percent of atopic dermatitis (AD) liability-scale heritability could be attributed to 31 susceptibility loci identified by using genome-wide association studies, with only 3 of them (IL13, IL-6 receptor [IL6R], and filaggrin [FLG]) resolved to protein-coding variants. OBJECTIVE: We examined whether a significant portion of unexplained AD heritability is further explained by low-frequency and rare variants in the gene-coding sequence. METHODS: We evaluated common, low-frequency, and rare protein-coding variants using exome chip and replication genotype data of 15,574 patients and 377,839 control subjects combined with whole-transcriptome data on lesional, nonlesional, and healthy skin samples of 27 patients and 38 control subjects. RESULTS: An additional 12.56% (SE, 0.74%) of AD heritability is explained by rare protein-coding variation. We identified docking protein 2 (DOK2) and CD200 receptor 1 (CD200R1) as novel genome-wide significant susceptibility genes. Rare coding variants associated with AD are further enriched in 5 genes (IL-4 receptor [IL4R], IL13, Janus kinase 1 [JAK1], JAK2, and tyrosine kinase 2 [TYK2]) of the IL13 pathway, all of which are targets for novel systemic AD therapeutics. Multiomics-based network and RNA sequencing analysis revealed DOK2 as a central hub interacting with, among others, CD200R1, IL6R, and signal transducer and activator of transcription 3 (STAT3). Multitissue gene expression profile analysis for 53 tissue types from the Genotype-Tissue Expression project showed that disease-associated protein-coding variants exert their greatest effect in skin tissues. CONCLUSION: Our discoveries highlight a major role of rare coding variants in AD acting independently of common variants. Further extensive functional studies are required to detect all potential causal variants and to specify the contribution of the novel susceptibility genes DOK2 and CD200R1 to overall disease susceptibility.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Dermatitis Atópica/genética , Genotipo , Receptores de Orexina/genética , Fosfoproteínas/genética , Piel/metabolismo , Adulto , Estudios de Cohortes , Proteínas Filagrina , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Especificidad de Órganos , Polimorfismo Genético , Riesgo , Transcriptoma
9.
Allergol Int ; 70(3): 313-318, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33962863

RESUMEN

Adverse allergic reactions due to the administration of the vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns. Current analyses provided by the Center for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of mRNA-1273 and BNT162b2 vaccines administered, respectively. Although rather low, such rates could have importance due to the uncommon fact that a large majority of the world population will be subjected to vaccination with the aforementioned vaccines in the following months and vaccination will most likely be necessary every season as for influenza vaccines. Health regulators have advised that any subject with a previous history of allergy to drugs or any component of the vaccines should not be vaccinated, however, certain misunderstanding exists since allergy to specific excipients in drugs and vaccines are in occasions misdiagnosed due to an absence of suspicion to specific excipients as allergenic triggers or due to inaccurate labeling or nomenclature. In this review, we provide an updated revision of the most current data regarding the anaphylactic reactions described for BNT162b2 vaccine, mRNA-1273 vaccine, and AZD1222 vaccine. We extensively describe the different excipients in the vaccines with the potential to elicit systemic allergic reactions such as polyethylene glycol (PEG), polysorbates, tromethamine/trometamol, and others and the possible immunological mechanisms involved.


Asunto(s)
Anafilaxia/inducido químicamente , Anafilaxia/prevención & control , Vacunas contra la COVID-19/efectos adversos , Hipersensibilidad a las Drogas/etiología , Excipientes/efectos adversos , Vacunación/efectos adversos , Vacuna nCoV-2019 mRNA-1273 , Anafilaxia/diagnóstico , Anafilaxia/inmunología , Animales , Vacuna BNT162 , Vacunas contra la COVID-19/administración & dosificación , ChAdOx1 nCoV-19 , Composición de Medicamentos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad a las Drogas/prevención & control , Excipientes/administración & dosificación , Humanos , Seguridad del Paciente , Medición de Riesgo , Factores de Riesgo
10.
Immunology ; 161(2): 83-93, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32687609

RESUMEN

Viral infections and atopic diseases are closely related and contribute to each other. The physiological deficiencies and immune mechanisms that underlie atopic diseases can result in a suboptimal defense against multiple viruses, and promote a suitable environment for their proliferation and dissemination. Viral infections, on the other hand, can induce per se several immunological mechanisms involved in allergic inflammation capable to promote the initiation or exacerbation of atopic diseases such as atopic asthma. In a world that is affected more and more by factors that significantly impact the prevalence of atopic diseases, coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome (SARS-CoV-2) is having an unprecedented impact with still unpredictable consequences. Therefore, it is of crucial importance to revise the available scientific literature regarding the association between common respiratory viruses and asthma, as well as the newly emerging data about the molecular mechanisms of SARS-CoV-2 infection and its possible relation with asthma, to better understand the interrelation between common viruses and asthma and its potential meaning on the current global pandemic of COVID-19.


Asunto(s)
Asma/inmunología , COVID-19/inmunología , Pulmón/inmunología , SARS-CoV-2/inmunología , Asma/epidemiología , Asma/fisiopatología , COVID-19/epidemiología , COVID-19/fisiopatología , COVID-19/virología , Citocinas/inmunología , Interacciones Huésped-Patógeno , Humanos , Mediadores de Inflamación/inmunología , Pulmón/fisiopatología , Pulmón/virología , Pronóstico
11.
Int Arch Allergy Immunol ; 181(5): 353-356, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32160611

RESUMEN

BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, with an increasing incidence in clinical practice. AD models have demonstrated that TGF-ß signaling is compromised in regulatory T cells (Tregs). OBJECTIVES: This study aimed to investigate the TGF-ß-dependent in vitro conversion of CD4+CD25- T cells derived from AD-patients into CD4+CD25+Foxp3+ induced Tregs (iTregs) in comparison to healthy controls. METHODS: To analyze in vitro iTreg conversion, human CD4+CD25- T cells were cultured on anti-CD3-coated plates in the presence of TGF-ß and IL-2 for up to 3 days. Consequently, the underlying mechanism of impaired CD4+CD25+Foxp3+ iTreg generation was explored by focusing on TGF-ß signaling. Finally, the functionality of iTregs was investigated. RESULTS: Conversion of CD4+CD25-Foxp3- into CD4+CD25+Foxp3+ iTregs was diminished in AD individuals. Impaired iTreg generation was accompanied by a reduced surface expression of GARP (glycoprotein A repetitions predominant), a marker for activated Tregs. A reduced expression of Smad3 mRNA was revealed in CD4+CD25- T cells. Interestingly, the suppressive quality of iTregs was found to be equal in cells derived from AD and healthy donors. CONCLUSION: The signaling effect of TGF-ß receptors on the suppressor quality of iTreg conversion is conserved. Impaired iTreg generation might be a reason for the lack of immune suppression in AD patients and contributes to the chronicity of the disease.


Asunto(s)
Dermatitis Atópica/inmunología , Activación de Linfocitos/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Anciano , Antígenos CD4/inmunología , Diferenciación Celular/inmunología , Femenino , Factores de Transcripción Forkhead/inmunología , Humanos , Técnicas In Vitro , Subunidad alfa del Receptor de Interleucina-2/inmunología , Masculino , Persona de Mediana Edad , Factor de Crecimiento Transformador beta/inmunología , Adulto Joven
12.
J Immunol ; 200(12): 4024-4035, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-29712772

RESUMEN

Type I IFN production of plasmacytoid dendritic cells (pDCs) triggered by TLR-signaling is an essential part of antiviral responses and autoimmune reactions. Although it was well-documented that members of the cytokine signaling (SOCS) family regulate TLR-signaling, the mechanism of how SOCS proteins regulate TLR7-mediated type I IFN production has not been elucidated yet. In this article, we show that TLR7 activation in human pDCs induced the expression of SOCS1 and SOCS3. SOCS1 and SOCS3 strongly suppressed TLR7-mediated type I IFN production. Furthermore, we demonstrated that SOCS1- and SOCS3-bound IFN regulatory factor 7, a pivotal transcription factor of the TLR7 pathway, through the SH2 domain to promote its proteasomal degradation by lysine 48-linked polyubiquitination. Together, our results demonstrate that SOCS1/3-mediated degradation of IFN regulatory factor 7 directly regulates TLR7 signaling and type I IFN production in pDCs. This mechanism might be targeted by therapeutic approaches to either enhance type I IFN production in antiviral treatment or decrease type I IFN production in the treatment of autoimmune diseases.


Asunto(s)
Células Dendríticas/metabolismo , Factor 7 Regulador del Interferón/metabolismo , Interferón-alfa/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Receptor Toll-Like 7/metabolismo , Células Cultivadas , Células HEK293 , Humanos , Leucocitos Mononucleares/metabolismo , Transducción de Señal/fisiología
13.
Andrologia ; 52(4): e13511, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32052474

RESUMEN

Male subfertility has been associated with bacterial infections and chronic inflammation. In this context, several studies investigated cytokine levels in seminal plasma, whereas interleukin-6 (IL-6) appears to be crucial. However, little is known about its receptor, the IL-6R expression on human spermatozoa. Thus, the aim of the present study was to screen spermatozoa for IL-6R expression and to identify its localisation. Semen samples of 137 patients (median age 37.69, SD ± 7.82) with subfertility were analysed. Sperm analysis including determination of IL-6 was performed following the World Health Organization criteria. Also, flow cytometry was performed for sperm IL-6R expression. IL-6R+ cells were used for immunofluorescence staining to identify receptor localisation. The results showed positive staining for IL-6R in the midpiece of spermatozoa. Furthermore, a significant correlation between sperm IL-6R expression, seminal plasma IL-6 and total sperm count could be demonstrated, whereas a negative correlation was observed in sperm IL-6R expression and motility. However, no statistical significance could be observed between IL-6R expression, vitality and morphology. Moreover, incubation of spermatozoa with IL-6 led to a slight but significant decrease in motility after 24 hr. These data suggest that IL-6R expression may play a role in impaired sperm function during inflammation.


Asunto(s)
Infertilidad Masculina/metabolismo , Receptores de Interleucina-6/metabolismo , Espermatozoides/metabolismo , Adulto , Humanos , Masculino , Persona de Mediana Edad
14.
Crit Rev Food Sci Nutr ; 59(1): 31-42, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-28799792

RESUMEN

Daily food processing has the potential to alter the allergenicity of foods due to modification of the physico-chemical properties of proteins. The degree of such modifications depends on factors such as processing conditions, type of food considered, allergenic content, etc. The impact of daily food processing like boiling, roasting, frying or baking on food allergenicity have been extensively studied. The influence of other thermal treatments such as microwave heating or pressure cooking on allergenicity has also been analyzed. Non-thermal treatment such as peeling impacts on the allergenic content of certain foods such as fruits. In this review, we give an updated overview of the effects of daily processing treatments on the allergenicity of a wide variety of foods. The different variables that contribute to the modification of food allergenicity due to processing are also reviewed and discussed.


Asunto(s)
Alérgenos/química , Alérgenos/inmunología , Culinaria , Hipersensibilidad a los Alimentos , Alimentos/clasificación , Análisis de los Alimentos , Humanos , Proteínas de Plantas
15.
J Immunol ; 198(8): 3033-3044, 2017 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-28275138

RESUMEN

FcεRII is a multifunctional low-affinity IgER that is involved in the pathogenesis of allergic, inflammatory, and neoplastic diseases. Although discrepancies in FcεRII-mediated functions are being increasingly recognized, the consequences of FcεRII activation are not completely understood. In this study, we evaluated the expression of FcεRII on human blood cells and found that it was primarily expressed on monocytes and B cells. Although IL-4 promoted expression of the FcεRIIb isoform on B cells and monocytes, the expression of the FcεRIIa isoform was not dependent on IL-4. Furthermore, FcεRII predominantly bound allergen-IgE complexes on B cells but not on monocytes. FcεRII-mediated allergen-IgE complex uptake by B cells directed Ags to MHC class II-rich compartments. FcεRII-bearing monocytes and B cells expressed high levels of the FcεRII sheddase a disintegrin and metalloproteinase 10, which implies that they are important sources of soluble FcεRII. Moreover, we identified that IgE immune complex stimulation of FcεRII activated intracellular tyrosine phosphorylation via Syk in B cells but not in monocytes. Importantly, FcεRII-mediated signaling by allergen-IgE immune complexes increased IFN-γ production in B cells of allergic patients during the build-up phase of allergen-specific immunotherapy. Together, our results demonstrate that FcεRII mediates cell type-dependent function in allergic reactions. In addition, the results identify a novel allergen-IgE complex/FcεRII/Syk/IFN-γ pathway in allergic responses and suggest that FcεRII may play a role in regulating allergic reactions via modulating IFN-γ production in B cells.


Asunto(s)
Linfocitos B/inmunología , Activación de Linfocitos/inmunología , Monocitos/inmunología , Receptores de IgE/inmunología , Hipersensibilidad Respiratoria/inmunología , Adulto , Anciano , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Hipersensibilidad , Immunoblotting , Inmunoprecipitación , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Transducción de Señal/inmunología
16.
J Allergy Clin Immunol ; 142(2): 497-509.e9, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29361332

RESUMEN

BACKGROUND: BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein. OBJECTIVE: We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma. METHODS: A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 µg, n = 60) or high dose (160 µg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC. RESULTS: Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year. CONCLUSIONS: Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated.


Asunto(s)
Alérgenos/inmunología , Epítopos de Linfocito B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Polen/inmunología , Precursores de Proteínas/inmunología , Rinitis Alérgica Estacional/inmunología , Vacunas/inmunología , Adolescente , Adulto , Alérgenos/genética , Desensibilización Inmunológica/métodos , Método Doble Ciego , Epítopos de Linfocito B/genética , Femenino , Antígenos de Superficie de la Hepatitis B/genética , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Poaceae/inmunología , Polen/genética , Precursores de Proteínas/genética , Resultado del Tratamiento , Vacunación , Adulto Joven
17.
J Dtsch Dermatol Ges ; 17(4): 433-440, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30958934

RESUMEN

Only few diseases have been studied as extensively and on as many different levels in recent years as atopic dermatitis (AD). One of the reasons why AD is the focus of interest is that it is one of the most common chronic inflammatory skin diseases, affecting up to 30 % of children and 1-10 % of adults. Numerous complex alterations both on the genetic level as well as on the level of innate and adaptive immunity have been identified and form the basis for the characterization of different patient groups and the development of novel diagnostic and therapeutic approaches. Despite the complex pathophysiological and immunological differences, which are closely related to disease stage and severity, as well as the heterogeneity of individual trigger factors, treatment of AD - in particular that of moderate-to-severe AD - was long limited to merely symptomatic and relatively nonspecific immunosuppressive approaches. Since the approval of the first biologic for the treatment of moderate-to-severe adult AD (commercially available in Germany since late 2017), there has been some movement in the field of AD management. The present review highlights recent pathophysiologic insights. Advances in research allow for better characterization of certain patient subgroups and different disease manifestations. In addition, they form the basis of current and future developments in the field of precision medicine in AD.


Asunto(s)
Dermatitis Atópica/inmunología , Dermatitis Atópica/fisiopatología , Piel/inmunología , Inmunidad Adaptativa , Adulto , Niño , Comorbilidad , Dermatitis Atópica/microbiología , Predisposición Genética a la Enfermedad , Alemania/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Microbiota/inmunología , Índice de Severidad de la Enfermedad , Piel/microbiología
18.
Am J Hum Genet ; 96(1): 104-20, 2015 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-25574825

RESUMEN

Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21-22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features.


Asunto(s)
Hibridación Genómica Comparativa , Dermatitis Atópica/genética , Estudio de Asociación del Genoma Completo , Psoriasis/genética , Alelos , Estudios de Casos y Controles , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 6/genética , Estudios de Cohortes , Sitios Genéticos , Humanos , Modelos Logísticos , Complejo Mayor de Histocompatibilidad/genética , Polimorfismo de Nucleótido Simple , Control de Calidad , Reproducibilidad de los Resultados
19.
Int Arch Allergy Immunol ; 177(1): 35-39, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29879702

RESUMEN

Roasting has been implicated in the increase of peanut allergenicity due to the chemical reactions that occur during the process. However, this increase is not fully understood, and little information is available regarding the role of roasted peanut allergens in the initial phase of allergy, where dendritic cells (DCs) play a key role. We sought to analyze differences in the internalization of Ara h 3 from raw and roasted peanut by immature monocyte-derived DCs (MDDCs) and the implication of the mannose receptor in the uptake. Ara h 3 was purified from raw and roasted peanut (Ara h 3-raw and Ara h 3-roas) and labeled with a fluorescent dye. The labeled allergens were added to MDDCs obtained from 7 donors and internalization was analyzed after 10, 30, and 120 min by flow cytometry. In parallel, mannan, which blocks the mannose receptor, was added 30 min before adding the labeled allergens. Results showed that the internalization of Ara h 3-roas by MDDCs was significantly increased at every time point. However, the increase in the internalization of Ara h 3-raw was only significant after 2 h of incubation. Ara h 3-roas had an enhanced capacity to be internalized by MDDCs in comparison with Ara h 3-raw at every time point. Blocking the mannose receptor decreased the internalization of Ara h 3-roas but not Ara h 3-raw. In conclusion, the internalization of Ara h 3-roas by the MDDCs is enhanced when compared to Ara h 3-raw, and the mannose receptor might be implicated in this enhancement.


Asunto(s)
Antígenos de Plantas/inmunología , Arachis/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Proteínas de Plantas/inmunología , Diferenciación Celular , Células Cultivadas , Células Dendríticas/citología , Endocitosis , Humanos , Inmunoglobulina E/inmunología , Lectinas Tipo C/metabolismo , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Monocitos/citología , Monocitos/inmunología , Monocitos/metabolismo , Hipersensibilidad al Cacahuete/inmunología , Hipersensibilidad al Cacahuete/metabolismo , Receptores de Superficie Celular/metabolismo
20.
Int Arch Allergy Immunol ; 175(1-2): 36-43, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29342467

RESUMEN

BACKGROUND: Soybean is one of the 8 foods that causes the most significant rate of food allergies in the USA and Europe. Thermal processing may impact on the allergenic potential of certain foods. We aimed to investigate modifications of the IgE-binding properties of soybean proteins due to processing methods that have been previously found to impact on the allergenicity of legumes such as peanut. METHODS: Soybean seeds were subjected to different thermal processing treatments. To evaluate their impact on the IgE-binding capacity of soybean proteins, individual sera from 25 patients sensitized to soybean were used in in vitro immunoassays. Detection of specific soybean allergens in untreated and treated samples was carried out with specific monoclonal and polyclonal antibodies. In vivo studies of skin prick testing (SPT) were also performed. RESULTS: The IgE reactivity of soybean was resistant to boiling up to 30 min, and this treatment had a higher impact when applied for 60 min. Treatment that combined heat and pressure produced a fragmentation of proteins in both soluble and insoluble fractions that went along with a decreased capacity to bind IgE and reduced the SPT wheal size. However, allergens such as 7S globulins survived this treatment. CONCLUSIONS: Thermal-processing methods able to attenuate the capacity of soybean proteins to bind IgE may contribute to the improvement of food safety and could constitute a potential strategy for the induction of tolerance to soybean.


Asunto(s)
Alérgenos/metabolismo , Hipersensibilidad a los Alimentos/inmunología , Glycine max/inmunología , Inmunoglobulina E/metabolismo , Proteínas de Plantas/metabolismo , Adulto , Alérgenos/inmunología , Culinaria , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Proteínas de Plantas/inmunología , Unión Proteica , Pruebas Cutáneas , Glycine max/química , Temperatura de Transición
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