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1.
Int Arch Allergy Immunol ; 184(6): 587-597, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36882015

RESUMEN

INTRODUCTION: Macrophages play a central role in balancing the immune response by switching phenotypes between the M1 and M2 profiles according to a delicate equilibrium. Based on a previous clinical trial (NCT03649139), this study aimed to evaluate the change in M2 macrophages during pollen exposure in seasonal allergic rhinitis (SAR). METHODS: Nasal symptom scores were recorded. Peripheral M2 macrophages were investigated according to cell surface markers, and M2-associated cytokine/chemokine release in serum and nasal secretion were assessed. In vitro pollen stimulation tests were performed, and polarized macrophage subsets were analyzed by flow cytometry. RESULTS: Compared to baseline, the percentage of peripheral CD163+ M2 macrophages in CD14+ monocytes increased during the pollen season (p < 0.001) and at the end of treatment (p = 0.004) in the SLIT group. The percentage of CD206+CD86- M2 cells in M2 macrophages during the pollen season was higher than that at baseline and at the end of SLIT. On the other hand, the percentage of CD206-CD86+ M2 cells in M2 macrophages significantly increased at the end of treatment in the SLIT group compared to baseline (p = 0.049), the peak pollen period (p = 0.017), and the placebo group (p = 0.0023). M2-associated chemokines CCL26 and YKL-40 were significantly increased during the pollen season in the SLIT group and remained higher at the end of SLIT than at baseline. Correspondingly, in vitro study demonstrated that Artemisia annua promoted M2 macrophage polarization in pollen-induced AR patients. CONCLUSION: Significant M2 macrophage polarization was promoted when patients with SAR were exposed to the allergen, either naturally exposed in pollen seasons or subjectively continuously exposed during the course of SLIT.


Asunto(s)
Rinitis Alérgica Estacional , Rinitis Alérgica Estacional/inmunología , Alérgenos/inmunología , Macrófagos/inmunología , Regulación hacia Arriba , Humanos , Polen/inmunología , Citocinas/inmunología
2.
Probiotics Antimicrob Proteins ; 15(4): 868-879, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-35113319

RESUMEN

Sensing of the intestinal microbiota by the host immune system is important to induce protective immune responses. Hence, modification of the gut microbiota might be able to prevent or treat allergies, mediated by proinflammatory Th2 immune responses. The aim was to investigate the ex vivo immunomodulatory effects of the synbiotics Pollagen® and Kallergen®, containing the probiotic bacterial strains Lactobacillus, Lacticaseibacillus and Bifidobacterium, in the context of grass pollen allergy. Peripheral blood mononuclear cells (PBMCs) from grass pollen-allergic patients and healthy controls were stimulated with grass pollen extract (GPE) and synbiotics and Gata3 expression and cytokine secretion analyzed. Monocyte-derived dendritic cells (MoDCs) cells were matured in the presence of GPE and synbiotics, co-cultured with autologous naïve T cells and maturation markers and cytokine secretion analyzed. GPE stimulation of PBMCs from grass pollen-allergic patients resulted in a significant higher production of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 compared to healthy controls. Gata3+CD4+ T cell induction was independent of the allergic status. The synbiotics promoted IL-10 and IFN-γ secretion and downregulated the GPE-induced Th2-like phenotype. Co-culturing naïve T cells with MoDCs, matured in the presence of GPE and synbiotics, shifted the GPE-induced Th2 cytokine release towards Th1-Th17-promoting conditions in allergic subjects. The investigated synbiotics are effective in downregulating the GPE-induced Th2 immune response in PBMCs from grass pollen-allergic patients as well as in autologous MoDC-T cell stimulation assays. In addition to increased IL-10 release, the data indicates a shift from a Th2- to a more Th1- and Th17-like phenotype.


Asunto(s)
Bifidobacterium , Células Dendríticas , Leucocitos Mononucleares , Rinitis Alérgica Estacional , Simbióticos , Humanos , Bifidobacterium/inmunología , Citocinas/inmunología , Células Dendríticas/inmunología , Células Dendríticas/microbiología , Lacticaseibacillus/inmunología , Lactobacillus/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/microbiología , Poaceae/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/microbiología , Inmunomodulación/inmunología , Células Cultivadas
3.
Front Immunol ; 14: 1274241, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38162647

RESUMEN

Aim: To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR). Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison. Results: Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, P = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, P = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26). Conclusion: Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians. Systematic review registration: PROSPERO (CRD42023460693).


Asunto(s)
Desensibilización Inmunológica , Inmunoterapia , Rinitis Alérgica , Inmunoterapia Sublingual , Niño , Humanos , Alérgenos/inmunología , Asma/tratamiento farmacológico , Desensibilización Inmunológica/efectos adversos , Desensibilización Inmunológica/métodos , Polen/inmunología , Rinitis Alérgica/terapia
6.
Sci Rep ; 11(1): 24426, 2021 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-34952907

RESUMEN

Allergies to grass pollen affects about 20% of the population worldwide. In the last few decades, the South American grass Cortaderia selloana (CS, Pampas grass) has expanded worldwide in a variety of countries including the USA, Australia and Western Europe. In many of these locations, CS has strikingly spread and has now been classified an invasive species. Many pernicious consequences of CS have been reported for local biodiversity, landscape and structures. However, the effect on human health has not been studied. To investigate this issue, we have chosen a European region on the northern cost of Spain where CS spread is overwhelming, Cantabria. We obtained CS pollen extract and analysed the allergenic reaction of 98 patients that were allergic to pollen of local grasses. We determined the skin reaction and the presence of specific IgE antibodies (sIgE) to CS or to a typical autochthonous grass, Phleum pratense. We also compared the seasonal symptoms with reported grass pollen counts in the area. The results strongly suggest that CS can cause respiratory allergies at a similar extent to the local grasses. Given that CS pollinises later than the local grasses, this would extend the period of grass allergies in the region for about three months every year, as stated by most of the patients. This is the first study reported on the effects of the striking expansion of CS on human health. Considering the strong impact that respiratory allergies have on the population, our results suggest that CS can currently constitute a relevant environmental health issue.


Asunto(s)
Alérgenos/inmunología , Hipersensibilidad , Poaceae/inmunología , Polen/inmunología , Rinitis Alérgica Estacional , Humanos , Hipersensibilidad/epidemiología , Hipersensibilidad/inmunología , Inmunoglobulina E/sangre , Rinitis Alérgica Estacional/epidemiología , Rinitis Alérgica Estacional/inmunología , España/epidemiología
7.
Biomed Res Int ; 2021: 5513611, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34840976

RESUMEN

OBJECTIVE: Determining sensitivity to allergens is an essential step in diagnosing children with allergic diseases. Chronic cough has remained poorly understood with causative triggers. The purpose of our study was to shed light on the relationship between sensitization to aeroallergens and chronic cough. METHODS: This population-based study examined children (aged 7 years to 13 years) between June and July 2016. The 1,259 children, 72 of whom (5.7%) had a chronic cough, and 1,187 of whom (94.3%) did not (controls), completed the questionnaire, but 1,051 children completed skin prick tests (SPTs) with eight aeroallergens. RESULTS: There were positive SPT results to at least 1 allergen in 549 children (52.2%). Sensitization to house dust mite (HDM) was most common (chronic cough = 46.9%; controls = 47.2%), followed by pollen (chronic cough = 21.9%; controls = 16.5%) in both groups, but there was no difference in allergic profile and sensitization to aeroallergen (P > 0.05 for all comparisons). Multivariable analysis with adjustment for confounding indicated that children who were in sensitization to pollen had an increased risk of chronic cough (aOR = 2.387; 95% CI: 1.115 to 5.111; P = 0.025). Multivariable analysis with adjustment for confounding indicated that children who were exposed to current smoking (aOR = 4.442; 95% CI: 1.831 to 10.776; P = 0.001) and mold (aOR = 1.988; 95% CI: 1.168 to 3.383; P = 0.011) were associated with chronic cough. CONCLUSION: Sensitization to pollen should be considered as a potential contributing factor to the development of chronic cough in school-aged children.


Asunto(s)
Alérgenos/inmunología , Tos/inmunología , Adolescente , Aerosoles , Alérgenos/administración & dosificación , Animales , Estudios de Casos y Controles , Niño , Enfermedad Crónica , Tos/diagnóstico , Tos/etiología , Estudios Transversales , Femenino , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Masculino , Análisis Multivariante , Polen/inmunología , Estudios Prospectivos , Pyroglyphidae/inmunología , República de Corea , Factores de Riesgo , Pruebas Cutáneas
8.
Allergol Immunopathol (Madr) ; 49(6): 60-62, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34761658

RESUMEN

BACKGROUND: Skin prick test (SPT) has the best positive predictive value to diagnose respiratory atopic diseases, including allergic rhinitis (AR), but the association of severity of allergic symptom and SPT reaction size has not been clearly determined yet. METHODS: In this a cross- sectional investigation, the severity of disease is classified using a visual analog scale for main symptoms, and SPT was conducted according to the principles of the European Academy of Allergy and Clinical Immunology. RESULTS: Thirty seven percent of the participants had at least one severe symptom. Patients with sensitivity to Alternaria (common allergens in humans) or tree pollens had more severe symptoms. We found that in patients who had sensitivity to Russian thistle pollen, wheal size >6 mm, was associated with more severe symptoms. CONCLUSION: Despite previous conflicts to rely on SPT test for starting immunotherapy, we recommend this test especially for patients sensitive to Alternaria, weed pollens, and tree pollens, considering the size of wheal in association with AR symptom severity.


Asunto(s)
Rinitis Alérgica , Urticaria , Alérgenos , Humanos , Polen/inmunología , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/epidemiología , Índice de Severidad de la Enfermedad , Pruebas Cutáneas , Urticaria/diagnóstico
9.
PLoS One ; 16(11): e0259914, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34784380

RESUMEN

In real life, humans are exposed to whole pollen grains at the air epithelial barrier. We developed a system for in vitro dosing of whole pollen grains at the Air-Liquid Interface (ALI) and studied their effect on the immortalized human bronchial epithelial cell line BEAS-2B. Pollen are sticky and large particles. Dosing pollen needs resuspension of single particles rather than clusters, and subsequent transportation to the cells with little loss to the walls of the instrumentation i.e. in a straight line. To avoid high speed impacting insults to cells we chose sedimentation by gravity as a delivery step. Pollen was resuspended into single particles by pressured air. A pollen dispersion unit including PTFE coating of the walls and reduced air pressure limited impaction loss to the walls. The loss of pollen to the system was still about 40%. A linear dose effect curve resulted in 327-2834 pollen/cm2 (± 6.1%), the latter concentration being calculated as the amount deposited on epithelial cells on high pollen days. After whole pollen exposure, the largest differential gene expression at the transcriptomic level was late, about 7 hours after exposure. Inflammatory and response to stimulus related genes were up-regulated. We developed a whole pollen exposure air-liquid interface system (Pollen-ALI), in which cells can be gently and reliably dosed.


Asunto(s)
Betula/química , Bronquios/citología , Perfilación de la Expresión Génica/métodos , Polen/inmunología , Bronquios/química , Bronquios/efectos de los fármacos , Línea Celular , Citocinas/genética , Células Epiteliales/química , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Fraccionamiento de Campo-Flujo , Regulación de la Expresión Génica , Humanos , Interleucina-17/genética , Interleucina-33/genética , Polen/efectos adversos
10.
Nat Commun ; 12(1): 5958, 2021 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-34645820

RESUMEN

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.


Asunto(s)
Alérgenos/inmunología , Hipersensibilidad a los Alimentos/microbiología , Microbioma Gastrointestinal/inmunología , Tolerancia Inmunológica , Hipersensibilidad Respiratoria/microbiología , Alérgenos/efectos adversos , Animales , Bacteroides/aislamiento & purificación , Bacteroides/metabolismo , Bifidobacterium longum/aislamiento & purificación , Bifidobacterium longum/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Clostridiales/aislamiento & purificación , Clostridiales/metabolismo , Alérgenos Animales/efectos adversos , Alérgenos Animales/inmunología , Huevos/efectos adversos , Faecalibacterium prausnitzii/aislamiento & purificación , Faecalibacterium prausnitzii/metabolismo , Femenino , Hipersensibilidad a los Alimentos/etiología , Hipersensibilidad a los Alimentos/inmunología , Humanos , Lipopolisacáridos/biosíntesis , Masculino , Leche/efectos adversos , Leche/inmunología , Nueces/efectos adversos , Nueces/inmunología , Polen/química , Polen/inmunología , Prunus persica/química , Prunus persica/inmunología , Pyroglyphidae/química , Pyroglyphidae/inmunología , Hipersensibilidad Respiratoria/etiología , Hipersensibilidad Respiratoria/inmunología , Ureasa/biosíntesis
11.
Cells ; 10(10)2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34685593

RESUMEN

TLR5 ligand flagellin-containing fusion proteins are potential vaccine candidates for many diseases. A recombinant fusion protein of flagellin A and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) modulates immune responses in vitro and in vivo. We studied the effects of rFlaA:Betv1 on bone marrow-derived macrophages (BMDMs). BMDMs differentiated from BALB/c, C57BL/6, TLR5-/-, or MyD88-/- mice were pre-treated with inhibitors, stimulated with rFlaA:Betv1 or respective controls, and analyzed for activation, cytokine secretion, metabolic state, RNA transcriptome, and modulation of allergen-specific Th2 responses. Stimulation of BMDMs with rFlaA:Betv1 resulted in MyD88-dependent production of IL-1ß, IL-6, TNF-α, IL-10, CD69 upregulation, and a pronounced shift towards glycolysis paralleled by activation of MAPK, NFκB, and mTOR signaling. Inhibition of either mTOR (rapamycin) or SAP/JNK-MAPK signaling (SP600125) resulted in dose-dependent metabolic suppression. In BMDM and T cell co-cultures, rFlaA:Betv1 stimulation suppressed rBet v 1-induced IL-5 and IL-13 secretion while inducing IFN-γ production. mRNA-Seq analyses showed HIF-1a, JAK, STAT, phagosome, NLR, NFκB, TNF, TLR, and chemokine signaling to participate in the interplay of cell activation, glycolysis, and immune response. rFlaA:Betv1 strongly activated BMDMs, resulting in MyD88-, MAPK-, and mTOR-dependent enhancement of glucose metabolism. Our results suggest macrophages are important target cells to consider during restauration of allergen tolerance during AIT.


Asunto(s)
Alérgenos/inmunología , Antígenos Bacterianos/inmunología , Antígenos de Plantas/inmunología , Flagelina/inmunología , Proteínas Recombinantes de Fusión/inmunología , Animales , Proteínas Bacterianas/inmunología , Células Cultivadas , Glucosa/metabolismo , Macrófagos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas de Plantas/inmunología , Polen/inmunología
12.
Int Immunopharmacol ; 99: 108026, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34358858

RESUMEN

Japanese Cedar (JC) pollinosis is the most common seasonal allergic rhinitis in Japan. Throughout the JC pollen season, patients suffer from the allergic symptoms, resulting in a reduction of quality of life. Allergy immunotherapy (AIT) is an established treatment option for a wide range of allergens that unlike symptomatic treatments (e.g. antihistamines) may provide sustained immune tolerance. However, AIT, especially subcutaneous immunotherapy (SCIT) has a fatal anaphylaxis risk due to the use of crude allergen extracts. Consequently, development of allergen derivatives with substantially reduced anaphylactic potential is desirable. An allergen derivative that showed reduced IgE-binding and anaphylactic potential was developed through conjugation of native Cry j 1 (n Cry j 1), a major JC allergen, to the polysaccharide pullulan followed by chemical but non-covalent denaturation. The resulting Cry j 1 allergen derivative, Dn p-Cry j 1, showed reduced IgE-binding and IgE-mediated effector cell activation in vitro using an ELISA competition assay and a mast cell activation model (EXiLE). Reduced anaphylactic potential of Dn p-Cry j 1 in vivo was demonstrated using the rat passive cutaneous anaphylaxis (PCA) assay. The difference in anaphylactic potential of Dn p-Cry j 1 compared to n Cry j 1 in wild-type rats was of the same magnitude as the difference seen in the anaphylaxis reactions obtained with n Cry j 1 in wild-type rats and mast-cell deficient rats, indicating a dramatic reduction in anaphylactic potential of Dn p-Cry j 1. These results indicate that Dn p-Cry j 1 is a promising candidate for next-generation JC AIT.


Asunto(s)
Antígenos de Plantas/administración & dosificación , Desensibilización Inmunológica/métodos , Glucanos/administración & dosificación , Proteínas de Plantas/administración & dosificación , Rinitis Alérgica Estacional/terapia , Alérgenos/inmunología , Animales , Antígenos de Plantas/química , Antígenos de Plantas/inmunología , Cryptomeria/inmunología , Modelos Animales de Enfermedad , Glucanos/química , Glucanos/inmunología , Humanos , Mastocitos/inmunología , Ratones , Anafilaxis Cutánea Pasiva , Proteínas de Plantas/química , Proteínas de Plantas/inmunología , Polen/inmunología , Ratas , Rinitis Alérgica Estacional/sangre , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/inmunología
14.
Int Arch Allergy Immunol ; 182(12): 1226-1230, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34392241

RESUMEN

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.


Asunto(s)
Alérgenos/uso terapéutico , Conjuntivitis Alérgica/terapia , Desensibilización Inmunológica/métodos , Polen/inmunología , Rinitis Alérgica/terapia , Adolescente , Adulto , Anciano , Alérgenos/inmunología , Niño , Conjuntivitis Alérgica/inmunología , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Calidad de Vida , Estudios Retrospectivos , Rinitis Alérgica/inmunología , Resultado del Tratamiento , Adulto Joven
15.
Front Immunol ; 12: 599955, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34385997

RESUMEN

Allergen-specific immunotherapy (AIT) is a safe, effective treatment for respiratory allergies (such as moderate-to-severe allergic rhinoconjunctivitis) that are not controlled by symptomatic medications. The indications and contraindications for AIT have been defined in international guidelines and consensus statements. However, some of these contraindications are not evidenced- based but have been deduced from the theoretical risk of an interaction between AIT disease-modifying effect and immune or inflammatory comorbidities. In the absence of clinical trial evidence, the accumulation of experience as case reports can narrow the spectrum of absolute contraindications. The majority of international guidelines list HIV infection as a contraindication to AIT. Here, we describe two cases of safe, effective sublingual birch pollen AIT in HIV-positive patients undergoing concomitant antiretroviral therapy. A 32-year-old female and a 63-year-old male sensitized to tree pollen and with clinically confirmed birch pollen allergy underwent pre- and co-seasonal sublingual birch pollen AIT for three and two pollen seasons, respectively. The therapy was associated with a marked reduction in the frequency and intensity of allergic symptoms, and the reduced use of (symptomatic) rescue medication. Mild, local, treatment-emergent adverse events were noted throughout the course of treatment but resolved spontaneously. No serious adverse events were reported. In particular, there were no obvious harmful effects on the patients' immune status or viral load. Hence, sublingual birch pollen AIT proved to be effective and safe in two HIV-positive patients.


Asunto(s)
Desensibilización Inmunológica/métodos , Infecciones por VIH/terapia , Rinitis Alérgica Estacional/terapia , Administración Sublingual , Adulto , Alérgenos/inmunología , Betula/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Infecciones por VIH/inmunología , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Resultado del Tratamiento
16.
Peptides ; 145: 170628, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34411692

RESUMEN

About half of the US population is sensitized to one or more allergens, as found by a National Health and Nutrition Examination Survey (NHANES). The most common treatment for seasonal allergic responses is the daily use of oral antihistamines, which can control some of the symptoms, but are not effective for nasal congestion, and can be debilitating in many patients. Peptide immunotherapy is a promising new approach to treat allergic airway diseases. The small size of the immunogens cannot lead to an unwanted allergic reaction in sensitized patients, and the production of peptides with sufficient amounts for immunotherapy is time- and cost-effective. However, it is not known what peptides are the most effective for an immunotherapy of allergens. We previously produced a unique monoclonal antibody (mAb) E58, which can inhibit the binding of multiple groups of mAbs and human IgEs from patients affected by the major group 1 allergens of ragweed (Amb a 1) and conifer pollens (Jun a 1, Cup s 1, and Cry j 1). Here, we demonstrated that a combined approach, starting from two linear E58 epitopes of the tree pollen allergen Jun a 1 and the ragweed pollen allergen Amb a 1, and residue modifications suggested by molecular docking calculations and peptide design could identify a large number of high affinity binding peptides. We propose that this combined experimental and computational approach by structural analysis of linear IgE epitopes and peptide design, can lead to potential new candidates for peptide immunotherapy.


Asunto(s)
Antialérgicos/farmacología , Anticuerpos Monoclonales/metabolismo , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacología , Animales , Antialérgicos/química , Antialérgicos/inmunología , Antígenos de Plantas/química , Antígenos de Plantas/inmunología , Epítopos/química , Epítopos/inmunología , Femenino , Humanos , Inmunoglobulina E/metabolismo , Inmunoterapia/métodos , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , Péptidos/inmunología , Extractos Vegetales/inmunología , Proteínas de Plantas/química , Proteínas de Plantas/inmunología , Polen/inmunología
17.
Mol Immunol ; 137: 42-51, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34214828

RESUMEN

Papaya is reported to trigger food and respiratory allergy. Here, we identified chymopapain Cari p 2 as an allergen that can sensitize atopic individuals through fruit consumption followed by respiratory hazards through pollen exposure. Recombinant Cari p 2 displayed IgE-reactivity with 78% of papaya allergic sera. rCari p 2 also displayed allergenic activity through basophil degranulation. rCari p 2 is correctly folded and showed irreversible denaturation in the melting curve. rCari p 2 displayed IgE-cross-reactivity with homologous cysteine proteases from kiwi and pineapple. Cari p 2 transcript was also detected in papaya pulps. rCari p 2 was resistant to pepsin digestion and retained IgE-reactivity after 60 minutes of pepsin digestion. In mouse model, rCari p 2 was found to elicit inflammatory responses in the lung and gastrointestinal epithelium. Hence, Cari p 2 is a newly characterized allergen with diagnostic and immunotherapeutic potential for managing allergic disorders in papaya sensitized individuals.


Asunto(s)
Alérgenos/inmunología , Quimopapaína/inmunología , Reacciones Cruzadas/inmunología , Frutas/inmunología , Polen/inmunología , Proteínas Recombinantes/inmunología , Adulto , Animales , Clonación Molecular/métodos , Proteasas de Cisteína/inmunología , Femenino , Hipersensibilidad a los Alimentos/inmunología , Humanos , Inmunoglobulina E/inmunología , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven
18.
Int Arch Allergy Immunol ; 182(12): 1194-1199, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34280917

RESUMEN

BACKGROUND: Gibberellin-regulated proteins (GRPs, Peamaclein) are allergens recently identified in plant-derived food allergy (FA), and little is known about the clinical manifestations of this allergic condition in the European population, especially in children. OBJECTIVE: Our study aimed to identify and characterize pediatric patients with pollen-FA due to GRP sensitization. METHODS: We retrospectively analyzed the charts of patients referred to the Allergy Unit of the Meyer Children's Hospital in Florence for suspected FA. Three main eligibility criteria based on the actual knowledge of GRP allergy were used to select patients deserving further investigations: (1) systemic reactions after consumption of fruit or an unknown culprit food, (2) positive skin prick tests to both cypress pollen and Pru p 3-enriched peach peel extracts, (3) negative in vitro test results for Pru p 3 serum-specific Immunoglobulin E (sIgE). We performed the in vitro test to determine the anti-rPru p 7 (Peamaclein) sIgE levels in the selected patients. RESULTS: We identified 10 pediatric patients with Pru p 7 allergy and described their characteristics. The use of our eligibility criteria showed a high accuracy in identifying these patients: 100% of the selected patients had positive in vitro results for Pru p 7. We therefore proposed a diagnostic algorithm for Pru p 7 allergy. CONCLUSION: This is the first case series of European pediatric patients with a demonstrated Peamaclein allergy. These findings broaden our knowledge on GRP allergy in pediatric populations and could help clinicians to suspect, diagnose, and manage this recently discovered plant-derived FA.


Asunto(s)
Alérgenos/inmunología , Antígenos de Plantas/efectos adversos , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/etiología , Frutas/efectos adversos , Giberelinas/inmunología , Proteínas de Plantas/inmunología , Prunus persica/efectos adversos , Adolescente , Algoritmos , Antígenos de Plantas/inmunología , Biomarcadores/sangre , Niño , Preescolar , Reglas de Decisión Clínica , Reacciones Cruzadas , Femenino , Hipersensibilidad a los Alimentos/inmunología , Frutas/inmunología , Humanos , Inmunoglobulina E/sangre , Masculino , Polen/efectos adversos , Polen/inmunología , Prunus persica/inmunología , Estudios Retrospectivos , Pruebas Cutáneas
19.
Mol Immunol ; 137: 84-93, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34242921

RESUMEN

BACKGROUND: Prosopis juliflora is a clinically relevant allergic sensitizer worldwide and shares cross-reactivity with allergens from several tree pollen and food. The present study aims to purify and immunobiochemically characterize a major allergen from Prosopis pollen. The allergen was further investigated for its cross-reactivity with legume allergens. METHODS: Prosopis extract was fractionated by Q Sepharose and Superdex 75 gel filtration column to purify the allergen. Specific IgE against purified protein was estimated via ELISA and immunoblot. The protein was subjected to mass spectrometric analysis. Glycan characterization was performed by Schiff staining and lectin binding assay followed by deglycosylation studies. The functional activity of the purified protein was evaluated by the basophil activation test. Cross-reactivity was assessed by inhibition studies with legume extracts. RESULTS: A 35 kDa protein was purified and showed 75% IgE reactivity with the patients' sera by ELISA and immunoblot. Glycan characterization of protein demonstrated the presence of terminal glucose and mannose residues. A reduction of 40% and 27% in IgE binding was observed upon chemical and enzymatic deglycosylation of the protein, respectively. The glycoprotein allergen upregulates the expression of CD203c on basophils which was significantly reduced upon deglycosylation, signifying its biological ability to activate the effector cells. The identified protein shared significant homology with Lup an 1 from the lupine bean. Immunoblot inhibition studies of the purified allergen with legume extracts underlined high cross-reactive potential. Complete inhibition was observed with peanut and common bean, while up to 70% inhibition was demonstrated with soy, black gram, chickpea, and lima bean. CONCLUSION: A 35 kDa vicilin-like major allergen was isolated from P. juliflora. The protein possesses glycan moieties crucial for IgE binding and basophil activation. Furthermore, the purified protein shows homology with Lup an 1 and exhibits cross-reactivity with common edible legume proteins.


Asunto(s)
Alérgenos/inmunología , Reacciones Cruzadas/inmunología , Fabaceae/inmunología , Prosopis/inmunología , Proteínas de Almacenamiento de Semillas/inmunología , Antígenos de Plantas/inmunología , Arachis/inmunología , Basófilos/inmunología , Femenino , Hipersensibilidad a los Alimentos/inmunología , Humanos , Inmunoglobulina E/inmunología , Masculino , Proteínas de Plantas/inmunología , Polen/inmunología , Pruebas Cutáneas/métodos
20.
Ann Allergy Asthma Immunol ; 127(4): 471-480.e4, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34311074

RESUMEN

BACKGROUND: Previous research has revealed that airborne pollen concentrations and phenology in allergenic plants are changing. In addition, variations in seasonal climate are known to affect pollen phenology in trees, weeds, and grasses. OBJECTIVE: To investigate localized trends in pollen concentrations and pollen phenology over time and the effect of seasonal climate variations. METHODS: We used daily pollen count concentrations from a National Allergy Bureau pollen counting station located in metropolitan Atlanta, Georgia, for 13 allergenic taxa. To evaluate long-term trends over time, we developed linear regression models for 6 pollen measures. To evaluate the effect of seasonal climate on phenology, we developed regression models using seasonal climate measures as independent variables and pollen measures as dependent variables. RESULTS: For several tree pollen taxa, pollen concentrations increased over time, including oak and juniper pollen. In multiple species, pollen seasons trended toward an earlier release throughout the 27-year period. Variations in seasonal climate did have an effect on pollen counts and the timing of pollen release but varied by taxa. Generally, warmer spring temperatures were associated with an earlier pollen release. In addition, increased precipitation from the preceding fall was associated with increased pollen concentration in the spring months. CONCLUSION: Allergenic pollen concentrations for several types of pollen are increasing and trending toward an earlier pollen release in Atlanta, Georgia. Warmer temperatures preceding the pollen season were associated with the earlier pollen release.


Asunto(s)
Contaminantes Atmosféricos/análisis , Alérgenos/análisis , Cambio Climático , Monitoreo del Ambiente/métodos , Polen/inmunología , Clima , Georgia , Humanos , Malezas , Poaceae , Rinitis Alérgica Estacional/inmunología , Estaciones del Año , Árboles
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