Clinical management of plant food allergy in patients sensitized to lipid transfer proteins is heterogeneous: identifying the gaps.

BACKGROUND AND OBJECTIVE: Patients sensitized to lipid transfer protein (LTP) present a wide clinical variability. The lack of practical diagnostic and therapeutic guidelines complicate their management. The aim of the study was to describe the clinical approach of Spanish allergists to this pathology using a survey designed by PICO method and subsequent Delphi approach validation. METHODS: Designed survey was answered by 224 allergists (75% women; 57.1% with >20 years of professional experience). Homogeneity regarding clinical practice on the main points of LTP allergy diagnosis was observed, except for patients with suspected NSAID hypersensitivity (44.6% frequently include LTP skin testing). Oral food challenges were not frequently performed (63.6% occasionally to never), and they were generally (75.5%) used to confirm tolerance. It was common to recommend fruit skins avoidance (77.2%) and maintaining consumption of foods to which patients are sensitised but tolerant (99.1%). RESULTS: There was heterogeneity on other dietary indications, modifications due to co-factors, or traces avoidance. Peach sublingual immunotherapy (SLIT) was considered very/quite effective by 55.9% of allergists. The majority (79.5%) consider SLIT indicated in <25% of LTP allergic patients, based on severity (95.2%), frequency of reactions (99.4%), allergy to multiple food families (97.4%), and the quality of life/nutrition impairment (91.5%). There was different practice on SLIT prescription based on co-factor involvement. CONCLUSION: These data suggest that there is a need to increase evidence to reduce the clinical practice heterogeneity in the management of LTP allergy.

Onset of Nut Allergy in a Pediatric Cohort: Clinical and Molecular Patterns in the AFRUSEN Study.

BACKGROUND AND OBJECTIVE: Nut allergy is a growing problem, yet little is known about its onset in children. Objective: To characterize the onset of nut allergy in children in southern Europe. METHODS: The study population comprised consecutive patients up to 14 years of age who visited allergy departments with an initial allergic reaction to peanut, tree nut, or seed. The allergy work-up included a clinical history, food challenge, skin prick testing, determination of whole-extract sIgE, and ImmunoCAP ISAC-112 assay. RESULTS: Of the 271 children included, 260 were first diagnosed with nut allergy at a mean age of 6.5 years and at a mean (SD) of 11.8 (21.2) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Onset of peanut allergy was more frequent in children ≤6 years and walnut in those aged >6 years (P=.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, polysensitization to nuts was detected by skin prick testing in 64.9% of patients, although this rate was lower among walnut-allergic children (54.7%) and peanut-allergic children (54.1%) (P<.0001). Sensitization to 2S albumins was predominant (75%), especially Jug r 1 (52.8%), whereas sensitization to lipid transfer proteins was less relevant (37%). CONCLUSION: In the population we assessed, the onset of nut allergy occurred around 6 years of age, slightly later than that reported in English-speaking countries. Walnut was the main trigger, followed by peanut. 2S albumin storage proteins, especially Jug r 1, were the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy.

Utility of neutrophil-to-lymphocyte ratio plus C-reactive protein for infection in systemic lupus erythematosus.

OBJECTIVE: To analyze the utility of neutrophil-to-lymphocyte ratio (NLR) plus C-reactive protein (CRP) to differentiate between infection and active disease in patients with SLE. METHODS: A cross-sectional study of a cohort of patients with SLE was carried out. Blood samples from four groups (patients without infection or active disease, patients with infection, patients with active disease, and patients with both infection and active disease) before therapeutic interventions were analyzed. We excluded patients with current malignancy, pregnancy, ischemic heart disease or use of antimicrobials during previous 7 days. Hematological cell count, CRP and cultures were obtained. We constructed receiver operating characteristic curves; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Forty patients were included. NLR cut-off ≥6.3 had sensitivity 70%, specificity 85%, PPV 83% and NPV 74% to detect patients with non-viral infections. A CRP cut-off ≥7.5 mg/L had sensitivity 90%, specificity 75%, PPV 78% and NPV 88% to detect infections regardless of SLE activity. Combination of CRP plus NLR improves the specificity to 90% and PPV to 88%. Excluding the group with both infection and active disease, CRP plus NLR expands specificity to 95% and NPV to 90%. CONCLUSION: In our experience, levels of CRP, particularly CRP plus NLR, were useful in differentiating patients with SLE from those with suspected non-viral infection regardless of the activity of the disease.

Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

Is Microarray Analysis Really Useful and Sufficient to Diagnose Nut Allergy in the Mediterranean Area?

BACKGROUND: Component-based diagnosis on multiplex platforms is widely used in food allergy but its clinical performance has not been evaluated in nut allergy. OBJECTIVE: To assess the diagnostic performance of a commercial protein microarray in the determination of specific IgE (sIgE) in peanut, hazelnut, and walnut allergy. METHODS: sIgE was measured in 36 peanut-allergic, 36 hazelnut-allergic, and 44 walnut-allergic patients by ISAC 112, and subsequently, sIgE against available components was determined by ImmunoCAP in patients with negative ISAC results. ImmunoCAP was also used to measure sIgE to Ara h 9, Cora 8, and Jug r 3 in a subgroup of lipid transfer protein (LTP)-sensitized nut-allergic patients (positive skin prick test to LTP-enriched extract). sIgE levels by ImmunoCAP were compared with ISAC ranges. RESULTS: Most peanut-, hazelnut-, and walnut-allergic patients were sensitized to the corresponding nut LTP (Ara h 9, 66.7%; Cor a 8, 80.5%; Jug r 3, 84% respectively). However, ISAC did not detect sIgE in 33.3% of peanut-allergic patients, 13.9% of hazelnut-allergic patients, or 13.6% of walnut-allergic patients. sIgE determination by ImmunoCAP detected sensitization to Ara h 9, Cor a 8, and Jug r 3 in, respectively, 61.5% of peanut-allergic patients, 60% of hazelnut-allergic patients, and 88.3% of walnut-allergic patients with negative ISAC results. In the subgroup of peach LTP-sensitized patients, Ara h 9 sIgE was detected in more cases by ImmunoCAP than by ISAC (94.4% vs 72.2%, P < .05). Similar rates of Cora 8 and Jug r 3 sensitization were detected by both techniques. CONCLUSIONS: The diagnostic performance of ISAC was adequate for hazelnut and walnut allergy but not for peanut allergy. sIgE sensitivity against Ara h 9 in ISAC needs to be improved.

Tumoral fibrosis effect on the radiation absorbed dose of (177)Lu-Tyr(3)-octreotate and (177)Lu-Tyr(3)-octreotate conjugated to gold nanoparticles.

The aim of this work was to evaluate the tumoral fibrosis effect on the radiation absorbed dose of the radiopharmaceuticals (177)Lu-Tyr(3)-octreotate (monomeric) and (177)Lu-Tyr(3)-octreotate-gold nanoparticles (multimeric) using an experimental HeLa cells tumoral model and the Monte Carlo PENELOPE code. Experimental and computer micro-environment models with or without fibrosis were constructed. Results showed that fibrosis increases up to 33% the tumor radiation absorbed dose, although the major effect on the dose was produced by the type of radiopharmaceutical (112Gy-multimeric vs. 43Gy-monomeric).

Are basophil activation and sulphidoleukotriene determination useful tests for monitoring patients with peach allergy receiving sublingual immunotherapy with a Pru p 3-enriched peach extract?

INTRODUCTION: Treatment of food allergy essentially consists of food avoidance, but immunotherapy with food is emerging as a new therapeutic option. OBJECTIVE: To evaluate clinical improvement and immunological changes in patients with peach allergy following sublingual immunotherapy (SLIT) with a Prup3 quantified peach extract. METHODS: A randomized, double-blind, placebo-controlled clinical trial with peach SLIT was conducted. We assessed clinical efficacy after 6 months of treatment by means of double-blind, placebo-controlled oral challenges with peach and also evaluated immunological changes (basophil activation test [BAT] and determination of sulphidoleukotriene production) following stimulation with peach peel and pulp, rPrup3, rMald 1, and rMal d 4 stimulation. We also measured specific IgE and IgG4 to Pru p3. RESULTS: After 6 months of SLIT (T6), the active group showed a 3-fold improvement in tolerance to Prup3 and a significant increase in IgE to rPrup3 and in sLT production following stimulation with peach peel and rPrup3. There was also a significant increase in BAT results after stimulation with rPrup3 at 1 month of SLIT (T1). Statistically significant between-group differences were only observed for BAT with peach peel and pulp at T1 and T6 and for BAT with rPru p3 at T6. No changes were observed in BAT with rMal d 1 or rMal d 4 or in IgG4 levels to nPrup3. CONCLUSIONS: SLIT with a Pru p 3 quantified peach extract is clinically effective and leads to an increase in basophil activation and sulphidoleukotriene production following stimulation with rPru p3 and peach peel in the first months of treatment.

Multifunctional radiolabeled nanoparticles for targeted therapy.

Nanoparticles can be near infrared (NIR)-fluorescent (e.g., gold nanoparticles, quantum dots or carbon nanotubes) or can have magnetic properties (e.g., iron oxide nanoparticles). These optical or magnetic properties can be exploited for use in thermal therapy and molecular imaging. Radiolabeled nanoparticles have proven to be promising tools in the diagnosis and therapy of malignant processes due to their multivalency and as multi-modal imaging agents. Furthermore, these radiopharmaceuticals may function simultaneously as both radiotherapy systems and thermal-ablation systems. This review examines the application of radiolabeled nanoparticles in the development of multifunctional nanosystems for targeted therapy.

Recommendations for the use of in vitro methods to detect specific immunoglobulin E: are they comparable?

Total and specific immunoglobulin (Ig) E can be detected in vitro using several commercially available methods. The largest share of the global market for these methods is held by the ImmunoCAP technique (Thermo Fisher, previously Phadia), Immulite (Siemens), and Hytec-288 (Hycor). Most comparative studies examine Immulite and ImmunoCAP, which differ methodologically but use similar units of measurement relative to the same standard of total IgE (WHO IgE Standard 75/502). Despite their similarity, these kits differ in their quantification of specific IgE, which varies depending on the allergen studied.Thus, specific IgE results obtained with ImmunoCAP and Immulite are not interchangeable. It is important to bear this in mind, especially when determining cutoff points as predictors of a response to oral challenge with specific food allergens. The method used in practice must be the same as the one in the publication guiding clinical decision making. We analyze differences between ImmunoCAP and ISAC microarray, 2 methods from the same manufacturer used to detect IgE to specific proteins (purified or recombinant).The results show that the IgE values obtained with ImmunoCAP are not equivalent to the corresponding values obtained with the ISAC microarray system.

Cross-reactivity syndromes in food allergy.

The immunological phenomenon of cross-reactivity has consequences for the diagnosis and treatment of certain food allergies. Once allergy to a particular food has been confirmed, positive test results are often obtained against other foods and, although less frequently, true clinical cross-reactivity is determined. This article reviews the relevant clinical aspects of food allergies in which the underlying mechanism is cross-reactivity between foods that are both related and unrelated taxonomically.

Oleaceae-induced pollinosis in an area with exposure to olive and ash trees.

BACKGROUND: Navarre, in Northern Spain, is an area with moderate exposure to olive and ash tree pollen. OBJECTIVE: To assess the relevance of ash as a cause of pollinosis in our region. METHODS: The study sample comprised 85 patients from Navarre with clinical symptoms of pollinosis. Specific immunoglobulin E (sIgE) was determined to Fra e 1, Ole e 1, and a mixture of amino- and carboxy-terminal domains of Ole e 9 (Ole e 9 NC) (ADVIA-Centaur). At the same time, the presence of sIgE to other pollen allergens was studied. Prick tests were performed with ash pollen (n=33) and olive pollen (n=85) and the symptomatic period was recorded (n=85). As a control group, we studied the serum of 98 patients with olive pollen allergy, intense exposure to olive pollen, and no exposure to ash. RESULTS: Sensitization to Oleaceae was detected in 24/85 patients in the study group (28.2%). In this group, the mean (SD) level of IgE to Fra e 1 was 8.5 (10) kU(A)/L and to Ole e 16.07 (7.88) kU(A)/L (P < .001). In the control group, these figures were 103.64 (132.19) kU(A)/L and 86.43 (118.5) kU(A)/L (P < .001), respectively. In all patients with positive sIgE to Fra e 1, IgE to Ole e 1 was also detected (concordance index, kappa = 1), both in the study group and in the control group. Patients who were sensitized to Fra e 1 did not present a longer symptomatic period and their symptoms did not have an earlier onset. CONCLUSION: We did not find evidence of clinically relevant sensitization to ash in Navarre.

Diagnosis and management of immunodeficiencies in adults by allergologists.

Primary immunodeficiencies (PIDs) are genetic diseases that cause alterations in the immune response and occur with an increased rate of infection, allergy, autoimmune disorders, and cancer. They affect adults and children, and the diagnostic delay, morbidity, effect on quality of life, and socioeconomic impact are important. Therapy (gamma-globulin substitution in most cases) is highly effective. We examine adult PIDs and their clinical presentation and provide a sequential and directed framework for their diagnosis. Finally, we present a brief review of the most important adult PIDs, common variable immunodeficiency, including diagnosis, pathogenesis, clinical signs, and disease management.

Click chemistry for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin.

(99m)Tc-HYNIC labeled Lys(3)-bombesin has shown specific binding to gastrin-releasing peptide receptors (GRP-r) over-expressed in cancer cells. Click chemistry offers an innovative functionalization strategy for biomolecules such as bombesin. The aim of this research was to apply a click chemistry approach for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin and to compare the in vitro MCF7 breast cancer cell uptake and biodistribution profile in mice with that of (99m)Tc-EDDA/HYNIC-Lys(3)-bombesin. The results suggest a higher lipophilicity for (99m)Tc(CO)(3)-triazole-Lys(3)-bombesin which explains its higher in vivo hepatobiliary elimination. Pancreas-to-blood ratio for (99m)Tc(CO)(3)-triazole-Lys(3)-bombesin was 4.46 at 3 h and both bombesin radiopharmaceuticals showed specific recognition for GRP receptors in MCF7 cancer cells. Click chemistry is a reliable approach for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin.

In vitro diagnosis of immediate allergic reactions to drugs: an update.

Evaluation of allergic reactions to drugs is difficult because of the poor sensitivity of in vivo tests, which makes controlled administration of the drug necessary to confirm the diagnosis. In vitro tests are important in order to avoid the risks of in vivo testing. In the present review, we describe the different methods for detecting immunoglobulin (Ig) E antibodies that are specific to drugs involved in the development of type I (immediate) reactions. The 2 main in vitro methods are immunoassays and the basophil activation test, both of which have sufficient sensitivity and specificity for the detection of specific IgE antibodies, although with a limited number of drugs, and they have proven complementary to in vivo methods. We show the importance of the allergological workup of the patient within less than 1 year from the occurrence of the allergic reaction in order to obtain positive results in both in vivo and in vitro tests.

Sublingual immunotherapy in peach allergy: monitoring molecular sensitizations and reactivity to apple fruit and Platanus pollen.

BACKGROUND: Peach allergy is prevalent, persistent, and potentially severe and as such is a target for immunotherapy. Our aims were to evaluate the profile of sensitization to Rosaceae allergens and the effects of sublingual peach immunotherapy on immunoglobulin (Ig) E levels to these allergens, to monitor for neosensitizations, and to check if this treatment modified other Rosaceae fruit and pollen-related sensitizations. METHODS: A double-blind placebo-controlled trial was conducted on 56 peach-allergic patients who received, sublingually, a standardized peach extract quantified in mass units of Pru p 3, or placebo for 6 months. IgE to recombinant (r) Mal d 1, rMal d 4, rPru p 3, and natural (n) Art v 3 and skin prick test (SPT) reactivity to Platanus pollen and apple extracts evaluated before treatment (T0), after 1 month (T1) and after and 6 months (T6) were recorded. RESULTS: In total, 18.5% of patients recognized rMal d 1, 83.3%, rPru p 3, 24.1%, rMal d 4, and 25.9% nArt v 3. IgE to Pru p 3 rose from T0 to T1 in both the active group (P = .003) and the placebo group (P = .022), and remained elevated at T6 in the active group (P = .001). IgE to other purified allergens did not change significantly and no relevant neosensitizations were detected. SPT reactions to peach decreased from T0 to T6 in the active group (P < 0.05). Reactivity to peach (T1 and T6) and apple (T6) was lower in the active group than in the control group. CONCLUSIONS: The main allergen was Pru p 3. Changes in rPru p 3 IgE levels and in peach and apple extract SPT were induced by sublingual immunotherapy.