Biomedical subjects

Adriano Mari

Publications and source records attributed to Adriano Mari.

11 recordsLinked to original sources

PubMed2006

Allergenic extracts for specific immunotherapy: to mix or not to mix?

Immunotherapy for allergic diseases give rise to questions about when a decision must be taken to define the number of extracts to be used in a single treatment. This represents a long-lasting matter of debate between American and European allergists, which seems to be without real solution. Through the use of extract-based versus molecule-based diagnostic approaches we suggest a possible solution to this controversial issue. We used four model patients previously tested with allergenic extracts and later on selected on the basis of a panel of available allergenic molecules. Their reactivity patterns in term of extracts and molecules were compared and the decision for allergenic extract immunotherapy was made choosing either the 'classical' approach or the molecular approach. From our study it seems that molecules could offer the solution to the 'mixing' issue of allergenic extracts. This innovative approach seems to provide a solution for both the American and the European approach.

Adult↗

PubMed2006

Delayed allergic reaction to suxamethonium driven by oligoclonal Th1-skewed CD4+CCR4+IFN-gamma+ memory T cells.

BACKGROUND: Muscle relaxants represent the drugs most frequently involved in intraoperative anaphylaxis during surgical procedures. Our aim was to report the case of a delayed reaction to suxamethonium and analyze specific T cell lines with regard to their specificity, phenotype and cytokine profile. METHODS: We generated a drug-specific T cell line from a biopsy at the site of positive intradermal reactions and analyzed the immunophenotype, T cell receptor Vbeta domain expression and cytokine profile. RESULTS: T cells isolated from positive intradermal test reactions to suxamethonium showed a strict dose-dependent proliferation in response to drug-pulsed autologous antigen-presenting cells. The drug-specific CD4+ T cells were oligoclonal memory CD3+CD4+ T cells and expressed the skin homing receptors cutaneous lymphocyte antigen (CLA) and CCR4. Furthermore CD4+ suxamethonium-reactive T cell lines were IFN-gamma-positive and synthesized high levels of IFN-gamma and TNF-alpha. CONCLUSION: The study describes a delayed hypersensitivity to suxamethonium, driven by an oligoclonal T helper cell 1-skewed CD4+ memory T cell population, expressing the skin homing receptors CLA and CCR4.

Adjuvants, Anesthesia↗

PubMed2006

Component-resolved diagnostics in food allergy.

PURPOSE OF REVIEW: The purpose of this paper is to review and discuss recent studies on component-resolved diagnostics in food allergy, involving panels of pure allergen molecules or arrays of peptides derived from allergen sequences, and to summarize the reporting of new food allergens during the past 2 years. RECENT FINDINGS: Several component-resolved diagnostic studies in food allergy suggest that the use of panels of allergen molecules may allow refined clinical information to be obtained on the likelihood or severity of an allergic food reaction and regarding diagnostic specificity. Further, in some studies the use of pure allergen molecules has led to a clearly higher sensitivity of the immunoglobulin E immunoassay compared with conventional allergen extracts. SUMMARY: While common diagnostic methods in allergy assess the presence or absence of allergen-specific sensitization, to date, no in-vitro or in-vivo test exists which exhibits full correlation with clinical food allergy. A multitude of recently reported findings and observations indicate that molecular analysis of allergen sensitization pattern may serve to enhance the clinical utility of immunoglobulin E antibody-based allergy diagnostics. Pure natural and recombinant allergen molecules as well as panels of synthetic peptides have been used for this purpose.

Allergens↗

PubMed2005

Importance of databases in experimental and clinical allergology.

Information technology (IT) is leading us to reconsider some of the approaches we have been using in both basic research and clinical work in allergology. Resources mainly coming from the advent of the Internet are further amplified by the parallel development of other new tools, such as molecular biology and nanotechnology. These three powerful tools are now available and are cross-linked to a certain degree to express their power when applied to biomedical fields. Bioinformatics applied to allergy simplifies our way of handling an increasing wealth of knowledge. This review assesses the current status of allergen databases that are mainly dedicated to sequence homology collection for computational purposes. Whether or not they integrate features that are now typical of IT in other biomedical fields is analyzed as well. The results of these analyses are discussed with a view to the critical need of integrating biochemical data with clinical, epidemiological information and how this goal can be reached by the use of proteomic microarrays for IgE detection. Future directions for a more comprehensive use of allergen databases are proposed.

Allergens↗

PubMed2005

The oral allergy syndrome: improved diagnostic and treatment methods.

PURPOSE OF REVIEW: The aim of this article is to review recent clinical and molecular findings related to the oral allergy syndrome in order to define its relevance in the field of food allergy, describe current diagnostic approaches and discuss attempts to use specific immunotherapy for treatment. RECENT FINDINGS: New allergenic sources causing the oral allergy syndrome have been reported. Their allergenic molecules have been identified. In most of those studies oral allergy syndrome is reported as a clinical manifestation among more severe ones. Some of the molecules generally considered not to be at risk for severe reactions have been demonstrated to pose a threat for inducing generalized reactions. Some studies tried to assess the usefulness of immunotherapy with birch pollen extract by either subcutaneous or sublingual routes for the treatment of associated food allergies. In most of the cases, a well defined study design and a molecular approach at different study levels are lacking and thus the value of the obtained results is limited. To date, no final conclusion can be drawn on the basis of reported results. SUMMARY: The knowledge about the highly prevalent phenomenon of oral allergy syndrome is still incomplete, in respect to both, epidemiology and foods inducing symptoms. It is very important to reach consensus on several aspects of this food-induced allergic disease. Further studies are required to highlight whether immunotherapy using co-recognized inhalant allergens is an effective way of curative treatment, or if co-treatment with purified pollen-related food allergens will be required to obtain a long-lasting effect.

Desensitization, Immunologic↗

PubMed2004

Generation of an allergy vaccine by disruption of the three-dimensional structure of the cross-reactive calcium-binding allergen, Phl p 7.

The grass pollen allergen, Phl p 7, belongs to a family of highly cross-reactive calcium-binding pollen allergens. Because Phl p 7 contains most of the disease-eliciting epitopes of pollen-derived calcium-binding allergens, hypoallergenic variants were engineered according to the x-ray crystal structure of Phl p 7 for allergy vaccination. In three recombinant variants, amino acids essential for calcium binding were mutated, and two peptides comprising the N- and C-terminal half were obtained by synthetic peptide chemistry. As determined by circular dichroism analysis and size exclusion chromatography coupled to mass spectrometry, recombinant mutants showed altered structural fold and lacked calcium-binding capacity, whereas the two synthetic peptides had completely lost their structural fold. Allergic patients' IgE Ab binding was strongest reduced to the variant containing two mutations in each of the two calcium-binding sites and to the peptides. Basophil histamine release and skin test experiments in allergic patients identified the peptides as the vaccine candidates with lowest allergenic activity. Immunization of rabbits with the peptides induced IgG Abs that blocked allergic patients' IgE binding to Phl p 7 and inhibited allergen-induced basophil degranulation. Our results indicate that disruption of an allergen's three-dimensional structure represents a general strategy for the generation of hypoallergenic allergy vaccines, and demonstrate the importance of allergen-specific IgG Abs for the inhibition of immediate allergic symptoms.

Allergens↗

PubMed2004

IgE sensitization profiles toward green and gold kiwifruits differ among patients allergic to kiwifruit from 3 European countries.

BACKGROUND: Kiwifruits have become a major elicitor of plant food allergy. Until recently, the only species of kiwifruit grown commercially was the common green-fleshed Actinidia deliciosa cv Hayward. In 1999, the yellow-fleshed cultivar Actinidia chinensis cv Hort16A was introduced into the international market. OBJECTIVE: We compared the allergen compositions of green and gold kiwifruits and assessed the sensitization patterns of patients with kiwifruit allergy toward both varieties. METHODS: Sera from 90 patients with kiwifruit allergy from Austria, central Italy, and the Netherlands were tested for IgE binding to green and gold kiwifruit protein extracts and to purified actinidin, the major kiwifruit allergen, by ELISA. In addition, ELISA inhibitions and immunoblots were performed with selected sera. Relevant allergens were identified by N-terminal sequencing and immunoblotting with allergen-specific antibodies. RESULTS: IgE immunoblotting showed marked differences in the allergen compositions of green and gold kiwifruit extracts. Phytocystatin, a novel plant food allergen, and a thaumatin-like protein were identified as allergens common for both cultivars. Two allergens with homologies to chitinases were found in gold kiwifruits, whereas actinidin was detected exclusively in green kiwifruits. Patients from Central Europe and central Italy showed distinct sensitization profiles toward green and gold kiwifruit extracts as well as actinidin. Whereas sera from Austrian and Dutch patients mainly recognized green kiwifruit extract and actinidin, almost all Italian sera showed IgE binding to both kiwifruit species, but only half of them contained actinidin-specific IgE. Green and gold kiwifruit extracts were shown to be highly cross-reactive as determined by IgE ELISA inhibition. CONCLUSION: The presence of common allergens and the IgE cross-reactivity to green kiwifruit qualifies gold kiwifruit as a potential new allergen source for patients allergic to green kiwifruits.

Actinidia↗

PubMed2004

Is there a causative role for tetanus toxoid vaccination in the development of allergy-like symptoms and in the increasing prevalence of atopic diseases?

Allergic diseases are a worldwide health problem. They mainly affect people living in developed countries where an increasing prevalence of allergy symptoms has been recorded in the last 20-30 years. The cause of this increase is still disputed, and, among others, the "hygiene hypothesis" supported the concept that relevant changes in lifestyle could have a relationship with the phenomenon. More recently the recorded parallel increase in autoimmune diseases has suggested to consider the "hygiene hypothesis" as a cause of a more general disregulation of the immune system leading to both allergy and to autoimmunity. Here are reported a series of observations, evidence, and data from the literature leading to a different hypothesis. The key points are: (1) the presence of two subsets of patients having allergy symptoms based on an IgE-mediated mechanism or not; (2) the positive results obtained with the autologous serum skin test in either cutaneous or respiratory affected subjects, mainly in children and adult females; (3) the presence of IgG autoantibodies against the alpha-chain of the high affinity IgE receptor (FcepsilonRIalpha) in non-IgE-mediated urticaria and even in respiratory subjects; (4) the cross-reactivity between epitopes of the tetanus toxoid molecule and the FcepsilonRIalpha detected by means of an alpha-chain affinity purified IgG fraction; (5) the positive skin reactivity obtained using IgG anti-tetanus toxoid preparations in allergic and non-allergic volunteers. The presence of IgG autoantibodies actively generated by the population-based vaccination with tetanus toxoid could induce both mediator release from activated mast cell and Th2 cytokine production early in life. There are epidemiological evidences that tetanus toxoid vaccination could be linked with an increased tendency to have allergy symptoms. The different epidemiological distribution of non-IgE-mediated symptoms, mainly affecting young infants would be in agreement with the present hypothesis. The prevalent mother-to-child relationship in terms of risk for allergy symptoms could be explained with the trans-placenta transfer of IgG. A similar transfer could also take place through the mother milk during breast feeding. It may thus be hypothesized that the increased prevalence of allergic diseases could be caused by the generalized tetanus toxoid immunization procedure, progressively extended to most of the countries worldwide in the last 30-40 years. Both the induction of non-IgE-mediated symptoms caused by the mast cell activation via the anti-FcepsilonRIalpha IgG and the long lasting Th2 inflammation of affected tissues would be the inducing mechanisms. This hypothesis would re-configure part of the allergic diseases as a Th2 phenotypic expression of an autoimmune disease.

Causality↗

PubMed2003

Allergy-like asthma and rhinitis. A cross-sectional survey of a respiratory cohort and a diagnostic approach using the autologous serum skin test.

BACKGROUND: Chronic idiopathic urticaria is considered an allergy-like skin disorder, and in some cases an auto-reactivity caused by mast cell degranulating factors has been demonstrated. A positive reaction to the autologous serum skin test (ASST), reflecting the presence of factors capable to degranulate the mast cells, is regarded as a reliable in vivo diagnostic test in chronic urticaria patients. About one out of three patients complaining for rhinitis or asthma does not show sensitization to any allergenic source. No data are available on the application of ASST to respiratory patients. METHODS: A cohort of respiratory patients, aged 1 to 80 years, complaining about suspected respiratory symptoms was screened using a panel of inhalant allergens by means of SPT and IgE. Current and past information on skin and respiratory symptoms were recorded for each patient. Patients were divided in 'allergy' and 'allergy-like' whether or not they react to at least one allergenic source. Age and gender distribution were analyzed. A control group fulfilling criteria for chronic idiopathic urticaria (CIU) was selected as well. The ASST was applied to the control CIU group, to the allergy-like and allergy subsets, and to a group of 58 healthy adult subjects. RESULTS: Allergy and allergy-like patients were differently distributed in relation to age and gender. Allergy-like children were prevalent before age six, whereas the prevalence of allergics steadily increased with age representing the large majority of patients in late childhood. The ratio of allergy/allergy-like subjects continues to increase in adult males, whereas adult females represent the large majority of the adult patients mainly within the allergy-like subset. Fifty-eight percent of CIU control patients reacted to the ASST. Among allergy-like patients ASST was positive in 47% of the adults (male 26%, female 54%), and in 84% of the children (no gender differences). The percentage of reactive subjects increased in the adult allergy-like subset if a CIU was associated (65%). Eighty-six percent of the pediatric patients and 61% of the adults having an allergy respiratory disease associated with an allergy-like condition had a positive ASST reactivity. Pure allergy patients reacted in 73% and 40% of the cases in the children and adults subgroups, respectively. Forty-five percent of healthy controls reacted to the ASST as well, and statistically significant gender differences were still recorded. CONCLUSIONS: An ASST reactivity is reported for the first time in allergy-like respiratory patients. A higher prevalence of reactive subjects has been recorded in all the pediatric subsets without gender differences, whereas female reactivity is prevalent among adults. The ASST reactivity seems to parallel the patient distribution within the entire respiratory cohort. Further studies are needed to demonstrate that the serum factors causing the ASST reactivity in respiratory patients are the same as for CIU affected subjects. In the light of recent in vitro findings, the ASST reactivity of healthy subjects could lead to a new interpretation of the autologous serum reactivity.

Adolescent↗

PubMed2002

Molecular, structural, and immunologic relationships between different families of recombinant calcium-binding pollen allergens.

BACKGROUND: Calcium-binding plant allergens can be grouped in different families according to the number of calcium-binding domains (EF hands). OBJECTIVE: We sought to identify pollens containing crossreactive calcium-binding allergens and to investigate structural and immunologic similarities of members belonging to different families of calcium-binding allergens. METHODS: By means of multiple sequence alignment and molecular modeling, we searched for structural similarities among pollen allergens with 2 (Phl p 7, timothy grass; Aln g 4, alder), 3 (Bet v 3, birch) and 4 EF hands (Jun o 4, prickly juniper). Purified recombinant Aln g 4 and Jun o 4 were used to determine the prevalence of IgE recognition in 210 patients sensitized to different pollens and to search, by means of ELISA competition, for the presence of cross-reactive epitopes in pollens from 16 unrelated plant species. IgE cross-reactivity among the allergen families was studied with purified rPhl p 7, rAln g 4, rBet v 3, and rJun o 4 and 2 synthetic peptides comprising the N-terminal and C-terminal EF hands of Phl p 7 by means of ELISA competition. RESULTS: Structural similarities were found by using molecular modeling among the allergens with 2, 3, and 4 EF hands. Pollens from 16 unrelated plants contained Aln g 4- and Jun o 4-related epitopes. Twenty-two percent of the patients with multiple pollen sensitization reacted to at least one of the calcium-binding allergens. A hierarchy of IgE cross-reactivity (rPhl p7 > rAln g 4 > rJun o 4 > rBet v 3) could be established that identified rPhl p 7 as the EF-hand allergen containing most IgE epitopes in the population studied. CONCLUSION: The demonstration that members of different families of calcium-binding plant allergens share similarities suggests that it may be possible to use representative molecules for the diagnosis and therapy of allergies to EF-hand allergens.

Allergens↗

PubMed2002

IgE to cross-reactive carbohydrate determinants: analysis of the distribution and appraisal of the in vivo and in vitro reactivity.

BACKGROUND: IgE to cross-reacting carbohydrate determinants has already been described by several authors, but their function and distribution are still a matter of debate. In previous studies we showed how the presence of IgE to bromelain could be a useful and simple marker of the presence of IgE to carbohydrate epitopes. METHODS: A survey of 1,831 subjects with a suspected allergic respiratory disease has been carried out by detecting IgE to bromelain. Data were analysed on the basis of demographical and allergological parameters. To find out whether a glycoprotein is capable of triggering an allergic reaction, 1,076 subjects were also skin tested with several purified molecules bearing carbohydrate side chains differing in number, composition and complexity. RESULTS: An overall prevalence of 23% of positive IgE to cross-reacting carbohydrate determinants was recorded. Prevalence varied when subsets of non-allergic (5%), non-pollen-allergic (10%), and pollen-allergic (31%) subjects were considered. Prevalence further increased in subsets with multiple pollen sensitization (71%), and with a previous pollen immunotherapy course (46%), whereas minor differences were found in gender and age distribution. Almost all the allergenic extracts recorded negative in the skin test gave a positive IgE test in vitro. A higher correlation was found mainly with plant-derived allergenic extracts, whereas a lower one was recorded with mites and fungi. Horseradish peroxidase was the only glycoprotein capable of exerting a positive skin test in 21% of the subjects with IgE to cross-reacting carbohydrate determinants, 80% of them having IgE to the HRP molecule. CONCLUSIONS: IgE to cross-reacting carbohydrate determinants are common among the allergic population and the binding to skin test negative allergenic extracts further confirms their poor biological activity. Further studies on horseradish peroxidase should be carried out to define the role of the glycan side chains in its allergenic activity.

Allergens↗