Background
Autoimmune processes are considered to play a major role in the pathogenesis of chronic spontaneous urticaria (CSU). Very recently, interleukin 24 (IL‐24) has been identified as an ...immunoglobulin E (IgE) autoantigen in CSU. Some studies revealed that notably autologous serum skin test (ASST)‐positive CSU patients may benefit from autohemotherapy; however, the mechanisms of action remain unknown. We aimed to investigate the immunological effects of autologous serum injections in ASST‐positive CSU patients.
Methods
Sixty‐six ASST‐positive CSU patients were treated with weekly intramuscular autologous serum injections for 8 weeks and followed up for 12 weeks. Urticaria activity score (UAS7) and Dermatology Life Quality Index (DLQI) were assessed. The ASST was done at baseline, week 9 and week 21. Serum samples (baseline, weeks 9, 13 and/or 21) were analysed for the levels of IgE‐anti‐IL‐24 and immunoglobulin G (IgG)‐anti‐IL‐24 via ELISA and their ability to release histamine in basophils basophil histamine release assay (BHRA).
Results
Autologous serum therapy resulted in a substantial improvement in disease activity and quality of life after 8 and 20 weeks. Twenty‐eight percent and 34% of patients turned ASST‐negative in weeks 9 and 21, respectively, but there was no link between their response to treatment and changes of ASST results. Also, no significant or relevant changes in BHRA were observed. In contrast, autologous serum therapy significantly decreased IgE‐anti‐IL‐24 serum levels, but not IgG‐anti‐IL‐24 serum levels, in responders but not in non‐responders.
Conclusions
Our findings suggest that the immunological effects of autologous serum therapy include a reduction in IgE‐anti‐IL24 autoantibodies, which may contribute to the pathogenesis of CSU.
Summary
Background Peanuts are often consumed after roasting, a process that alters the three‐dimensional structure of allergens and leads to Maillard modification. Such changes are likely to affect ...their allergenicity.
Objective We aimed to establish the effect of thermal treatment mimicking the roasting process on the allergenicity of Ara h 1 and a mix of 2S albumins from peanut (Ara h 2/6).
Methods Ara h 1 and Ara h 2/6 were purified from raw peanuts and heated in a dry form for 20 min at 145 °C in the presence (R+g) or absence (R−g) of glucose, and soluble proteins were then extracted. Sera obtained from 12 well‐characterized peanut‐allergic patients were used to assess the IgE binding and degranulation capacities of the allergens.
Results Extensive heating at low moisture resulted in the hydrolysis of both Ara h 1 and Ara h 2/6. However, in contrast to Ara h 2/6, soluble R+g Ara h 1 formed large aggregates. Although the IgE‐binding capacity of R+g and R−g Ara h 1 was decreased 9000‐ and 3.6‐fold, respectively, compared with native Ara h 1, their capacity to elicit mediator release was increased. Conversely, both the IgE‐binding capacity and the degranulation capacity of R−g Ara h 2/6 were 600–700‐fold lower compared with the native form, although the presence of glucose during heating significantly moderated these losses.
Conclusions and Clinical Relevance Extensive heating reduced the degranulation capacity of Ara h 2/6 but significantly increased the degranulation capacity of Ara h 1. This observation can have important ramifications for component‐resolved approaches for diagnosis and demonstrates the importance of investigating the degranulation capacity in addition to IgE reactivity when assessing the effects of food processing on the allergenicity of proteins.
Cite this as: Y. M. Vissers, M. Iwan, K. Adel‐Patient, P. Stahl Skov, N. M. Rigby, P. E. Johnson, P. Mandrup Müller, L. Przybylski‐Nicaise, M. Schaap, J. Ruinemans‐Koerts, A. P. H. Jansen, E. N. C. Mills, H. F. J. Savelkoul and H. J. Wichers, Clinical & Experimental Allergy, 2011 (41) 1631–1642.
Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU).
Twenty CSU patients unresponsive to ...antihistamine treatment were enrolled in order to evaluate the correlations between HR test results and demographic features, quality of life, disease activity, clinical course, and autologous serum and plasma skin tests (ASST and APST).
All patients with positive HR test (9/9, 100%) had a more severe disease activity at onset (urticaria activity score, UAS > 2) when compared to negative HR test patients (5/11; p = 0.04). Quality of life questionnaire's results were not substantially different between HR positive and negative subgroups at baseline (p > 0.05), and results of HR test and ASST/APST did not co-segregate (p > 0.05). After 12 months, patients with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0.027).
Positive HR test may predict spontaneous CSU remission at 12 months.
Patent Blue V (PBV) is injected in order to map sentinel nodes during cancer staging procedures. Anaphylactic reactions, allegedly IgE antibody mediated, have been reported. The aim of the study was ...to explore the immunological mechanism of anaphylaxis to PBV. PBV allergen threshold basophil sensitivity, CD-sens, was performed on cells from nine patients diagnosed as having had adverse reactions to PBV. The mechanisms of the CD-sens were studied by immunological and immuno-chemical methods. Five of the nine patients had a positive CD-sens to PBV which was completely eliminated by washing the cells in phosphate buffered saline before allergen challenge. However, the positive CD-sens was completely reconstituted by incubating the cells in plasma or serum of that patient or the other PBV-anaphylactic patients for 15 min at room temperature. In some patients the factor mediating CD-sens was completely or partially destroyed by heating at +56°C for 30 min or being exposed to the low pH used for elution from anti-Ig columns. A 1000-fold excess of monoclonal IgE blocked the reconstitution by approximately 50%. Anaphylactic reactions to PBV are mediated by IgE antibodies giving a classical CD-sens reaction. However, the allergenic configuration seems to constitute a structure completely dependent on PBV, as a hapten, linked to a, so far, unknown carrier that seems to be unique for patients having experienced a PBV-induced reaction. Further studies are needed to characterize the postulated carrier.
Background
Sensitization to hazelnut allergens vary depending on the geographic origin and age of the patients. The objective of this study was to further investigate the allergenic activity of ...hazelnut allergens using sera from patients recruited in various European regions and presenting different sensitization patterns to hazelnut proteins.
Methods
Natural Cor a 11 and Cor a 9 were purified from hazelnut whereas Cor a 1 and Cor a 8 were produced as recombinant proteins (rCor a 1.04 and rCor a 8). Sera from hazelnut allergic patients were collected in France (n = 5), Switzerland (n = 2), Greece (n = 11) and Spain (n = 3), within the Europrevall project. Total and allergen‐specific IgE were quantified by enzyme allergosorbent test and IgE immunoblot were performed using pooled sera from birch‐pollen endemic region or from Greece. Histamine Release (HR) assays were performed with stripped basophils passively sensitized with individual sera and challenged by a hazelnut extract or the different hazelnut allergens.
Results
As previously described, hazelnut allergic patients from Mediterranean countries are mainly sensitized to the nsLTP Cor a 8 whereas patients from France and Switzerland are sensitized to pollen‐related allergens. Interestingly, an intermediate profile was evidenced in patients from Madrid. Hazelnut 7S globulin (Cor a 11) and 11S globulin (Cor a 9) were found to be minor allergens, recognized only by patients from Mediterranean countries. The biologic activity of the 4 tested allergens, analysed by HR assay, further confirmed the sensitization patterns, but also demonstrated the very high elicitation potency of Cor a 8.
Conclusions
This work, extending previously published researches, represents a step towards the better understanding of the complexity of hazelnut allergy and provides new data on the biological activity of hazelnut allergens and extracts.
Fish allergy is one of the most common food allergies in both children and adults and patients with allergic reactions to one fish species have in many cases been given the advice to avoid all fish, ...without further evaluation. The possible common reactivity between different fish species is not well studied. Because of this and a possible exploitation of fish species hitherto not much used in the Scandinavian diet ocean pout, eelpout and eel were evaluated. We examined the serological and biological cross‐reactivity of these species in double‐blind challenged‐confirmed codfish‐allergic patients using CAP, Maxisorp‐radio allergosorbent test (RAST) inhibition, western blot, skin prick test (SPT) and histamine release (HR). All 18 codfish allergic patients had specific IgE to ocean pout, eelpout and eel determined by Maxisorp‐RAST. All four fish species could induce basophil HR using blood from 16 of 18 patients and all patients tested reacted in SPT. This study demonstrates that patients with a verified clinical allergy to codfish in a high frequency express biological cross‐reactivity to other fish species. By RAST inhibition this common reactivity was shown to be a true cross‐reactivity.
Background: The aim of the study was to examine the diagnostic value of skin prick test (SPT), scratch‐chamber test (SCT), histamine release (HR) and specific immunoglobulin E (IgE) in birch‐allergic ...patients with oral allergy syndrome to apple.
Methods: Ten birch‐allergic patients with oral allergy syndrome to apple and 10 control subjects were included. All were tested with SPT, SCT, HR and specific IgE CAP, Pharmacia, Sweden and Magic Lite (ML), ALK‐ABELLÓ, Denmark.
Results: The SPT with apple, acetone extract of apple (A72) and commercial apple extract showed sensitivities of 0.80, 0.90 and 0.10, respectively.
The SCT with the same extracts showed sensitivities of 0.30, 0.50 and 0.20, respectively. The sensitivity of specific IgE to apple were 0.90 (CAP) and 0.10 (ML).
The sensitivity of the HR test was 90% (A72), and 25% using the commercial extract.
Conclusion: The SPT and HR test with apple and A72 showed a good diagnostic value with a sensitivity of more than 70% and a specificity of 100%.
The SCT showed a poor sensitivity to apple, A72 and commercial apple extract. The ML test was not suitable in detecting specific IgE to apple compared with the CAP test.
In daily practice a detailed case history about symptoms of oral allergy syndrome combined with a SPT with fresh apple peel or A72 will be useful.
The aim of the study was to develop and evaluate different methods of double‐blind, placebo‐controlled food challenge (DBPCFC) with apple. Three different DBPCFC models were evaluated: fresh apple ...juice, freshly grated apple, and freeze‐dried apple powder. All challenges were performed outside the pollen season and took place from 1997 to 1999. The freeze‐dried apple material was characterized by means of leukocyte histamine release (HR), skin prick test (SPT), and immunoblotting experiments. The study population consisted of birch pollen‐allergic patients with a history of rhinitis in the birch‐pollen season and positive specific IgE to birch. For comparison of the DBPCFC models, 65 patients with a positive open oral challenge with apple were selected. In the characterization of the freeze‐dried apple material, 46 birch pollen‐allergic patients were included. The IgE reactivity to apple was evaluated by measurement of specific IgE, HR, and SPT. Golden Delicious apples were used in all experiments. The results of this study showed that it was possible to perform DBPCFC with apple in birch pollen‐allergic individuals. The model with freshly squeezed apple juice had a low sensitivity and displayed a high frequency of reactions to placebo, probably due to the ingredients used for blinding. The sensitivity of the models with freshly grated apple and freeze‐dried apple powder was 0.74/0.60. An increase in sensitivity is desirable. The freeze‐dried apple powder proved to be useful for SPT, HR, and oral challenges, but further investigation of the stability and the allergenic profile of the material is needed.
The introduction of novel proteins into foods carries a risk of eliciting allergic reactions in individuals sensitive to the introduced protein. Therefore, decision trees for evaluation of the risk ...have been developed, the latest being proposed by WHO/FAO early in 2001. Proteins developed using modern biotechnology and derived from fish are being considered for use in food and other applications, and since allergy to fish is well established, a potential risk from such proteins to susceptible human beings exists. The overall aim of the study was to investigate the potential allergenicity of an Ice Structuring Protein (ISP) originating from an arctic fish (the ocean pout,
Macrozoarces americanus) using the newly developed decision tree proposed by FAO/WHO. The methods used were those proposed by FAO/WHO including amino acid sequence analysis for sequence similarity to known allergens, methods for assessing degradability under standardised conditions, assays for detection of specific IgE against the protein (Maxisorb RAST) and histamine release from human basophils. In the present paper we describe the serum screening phase of the study and discuss the overall application of the decision tree to the assessment of the potential allergenicity of ISP Type III. In an accompanying paper Food Chem. Toxicol. 40 (2002) 965, we detail the specific methodology used for the sequence analysis and assessment of resistance to pepsin-catalysed proteolysis of this protein. The ISP showed no sequence similarity to known allergens nor was it stable to proteolytic degradation using standardised methods. Using sera from 20 patients with a well-documented clinical history of fish allergy, positive in skin prick tests to ocean pout, eel pout and eel were used, positive IgE-binding in vitro to extracts of the same fish was confirmed. The sera also elicited histamine release in vitro in the presence of the same extracts. The ISP was negative in all cases in the same experiments. Using the proposed decision tree, we demonstrated the safety of the ISP to patients already sensitised to fish, as well as to individuals potentially susceptible to producing IgE responses to proteins. Furthermore, the practicability of the new decision tree was confirmed.
New foods may present a risk for food hypersensitive patients. Several examples exist of allergic reactions caused by cross-reactive plant-derived foods, and new foods should be scrutinised before ...introducing them to the market. We have evaluated the clinical and serological relevance of cross-reactivity between Nangai and pollen allergens.
Cross-reactivity was examined with Maxisorp RAST (radioallergosorbent test), RAST inhibition and Western blot, using sera from patients allergic to grass, birch and mugwort pollen. None of the patients reported having seen or eaten Nangai previously. To determine the biological and clinical relevance of the cross-reactivity, histamine release (HR) test, skin prick test (SPT) and food challenge were used.
There was prevalence for reactivity against Nangai in the group of pollen allergic patients. This cross-reactivity seems to be related--at least in part--to carbohydrate epitopes. Three out of 12 patients tested with Nangai were positive upon open challenge, but using double blind placebo controlled food challenge (DBPCFC) this could not be confirmed in two patients. The biological effects of Nangai on allergic patients were confirmed using HR and SPT.
The Nangai specific IgE found among pollen allergic patients addresses the need for control of new or changed foods before introduction to the market.
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