Metrics details. The mucosal immune system is in constant communication with the vast diversity of microbes present on body surfaces. The discovery of novel molecular mechanisms, which mediate host-microbe communication, have highlighted the important roles played by microbes in influencing mucosal immune responses. Many of the mechanisms being described are bacterial strain- or metabolite-specific. Microbial dysbiosis in the gut and the lung is increasingly being associated with the incidence and severity of asthma. In addition, the efficacy of specific therapeutics may be influenced by the microbiome and novel bacterial-based therapeutics should be considered in future clinical studies. An enormous number of microbes colonize the skin and mucosal body surfaces.
It is expressed in high levels on plasmacytoid dendritic cells and basophils and in low levels on monocytes, eosinophils, myeloid dendritic cells and subsets of haematologic progenitor cells. CCR3 is the receptor for Immunll type chemokines e. Following stimulation with allergen, the expression of different proteins is up-regulated on the surface of basophils [ 4 ], namely CD63 [ 8 ] and CDc [ 910 ].
CD63 is a lysosomal-associated membrane protein LAMPwhich is not expressed on the surface of resting basophils but only on the membrane of the granules inside the cells [ 8 ]. When the granules fuse with the plasmatic membrane of the basophils during degranulation, CD63 becomes expressed on the surface of basophils [ 10 ].
It is exclusively and constitutively abbbreviation immunol low levels on the surface of basophils and mast cells and its expression increases with cell activation.
CD63 and CDc are the most commonly used basophil activation markers. The laboratory procedure of the BAT consists of three stages: cell stimulation, cell staining and flow cytometry—Fig. Blood should be processed as soon abbreviatino possible after blood collection, as basophils lose their viability and reactivity over time. A small volume of blood c.
Crude allergen clin or purified or recombinant allergens can babreviation used for cell stimulation. Different allergen concentrations should be used, as the sensitivity of the basophils to specific allergen stimulation varies abbbreviation patients. The results of BAT can be determined in terms of percentage of basophils expressing the defined activation marker or in terms of mean fluorescence intensity MFI by calculating the stimulation index, i.
The former is usually used for CD63 as CD63 is not expressed in resting cells and its expression after activation is bimodal. The latter is usually used for CDc which is already expressed in resting cells and its increase following allergen stimulation is unimodal—Fig.
Dot plots and histograms showing the expression of CD63 and CDc on the surface of basophils in different conditions.
Unstimulated cells negative abbreviation and cells stimulated with peanut or with anti-IgE positive control are represented. The expression of CD63 is measured as the percentage of positive basophils left panel and the expression of CDc is measured as the stimulation index SIi. In allergic patients, allergen-induced basophil activation typically cpin in a bell-shaped dose—response curve, with increasing abbdeviation of the allergen usually 5—6 log difference leading to a progressive increase in the expression of the basophil activation markers until reaching a plateau—Fig.
Basophil reactivity and basophil sensitivity. Two examples of dose—response curves of basophil activation following stimulation with various concentrations of allergen kmmunol two different patients are represented.
There is a large degree of variability allergy the basophil immuol to allergen between individuals. CD-max is the maximal activation and corresponds to the maximum proportion abbreviaion activated basophils at any concentration of allergen [ 5 ]. First described by Johansson [ 13 ], CD sens is the inverse of the half-maximal effective concentration, i.
CD max and CD sens are measures of basophil reactivity and of basophil sensitivity, respectively.
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Basophil reactivity can be defined as the degree of basophil activation, i. Basophil sensitivity refers to the concentration of allergen at which basophils become activated and can be expressed as a percentage of the maximal effective dose e.
Shreffler and Patil [ 14 ] have proposed a novel parameter to measure basophil responses, the area under the dose—response curve, which has the advantage of combining basophil reactivity and basophil sensitivity. Allergj a recently published study [ 15 ], we assessed the utility of the BAT to diagnose peanut allergy in a well-characterized population of peanut allergic, peanut sensitized and non-sensitized children. We validated the diagnostic cut-offs in a prospectively and independently recruited population and the diagnostic performance of BAT was still very good in this second study population.
Case reports and small case series have suggested that BAT may also be useful to diagnose allergy to sesame [ 36 ] and to less qbbreviation elicitors of IgE-mediated food allergic reactions, such as rice [ 37 ] and short chain galacto-oligosaccharides present in prebiotics [ 38 ].
Existing studies are heterogeneous in most of these aspects, which limits their comparability and a wider application of the diagnostic cut-offs determined in specific studies. The criterion to diagnose each food allergy is allergen-specific and the diagnostic accuracy may not be the same for different allergens. Additionally, the cut-offs defined in one population are not necessarily directly transferrable to another population from a different geographical location assessed in a different Allergy centre.
One limitation of BAT is the fact that a small proportion of patients tested have non-responder basophils i. Additional challenges in translating the BAT from a research method to a diagnostic test in the clinic are related to the standardisation of the assay and its reproducibility and also to the cost-effectiveness of including BAT in the diagnostic approach of patients with suspected food allergy. These aspects have not yet been established and require further research.
The methodology adopted to perform the laboratory procedure and to analyse the flow cytometry data can have a significant impact on the results obtained for the BAT and, consequently, in its diagnostic accuracy. For example, identifying basophils using an anti-IgE antibody can activate the cells and alter the results obtained with a different method to identify the basophils.
The expression of certain basophil identification markers, such immunol CCR3 [ 42 ] and CD [ 43 ] can change following basophil activation. In a recent allergy, we described that in about a quarter of patients, the expression of CD, as allergy by flow cytometry, can be reduced following basophil activation and therefore lead to a significant loss-to-analyses of activated cells using methods that rely on this marker to identify basophils.
This could result in an increased number of misdiagnosis, particularly false-negatives, with important consequences for individual patients. Overall, as a diagnostic test, BAT has shown high specificity and positive predictive value. The high specificity is an important addition to existing allergy tests, such as SPT and sIgE, which have high sensitivity but are not very specific. The high specificity implies that a positive BAT confirms the diagnosis of food allergy with confidence but a negative BAT does not necessarily exclude the diagnosis.
Depending on the clin ratio and safety aspects, OFC can be done in patients where BAT provides an inconclusive result namely patients with non-responder basophils or in patients where BAT provides an inconclusive result and in patients where BAT was negative. The approach to decide about the need for OFC following BAT also depends on how the result of BAT clin considered in the context of the results of other allergy tests, either in combination, when all the results available are considered simultaneously, or sequentially, where BAT is performed only in patients who had equivocal or discordant results for the other allergy tests.
In our previously cited peanut study [ 15 ], we compared the performance of BAT with that of other allergy tests done in parallel. Considering single tests, the most accurate diagnostic test was the BAT. In order to make the most of the information available, the results of BAT can be used in combination with the results of other tests [ 15174445 ].
However, generally, the more tests used, the higher the diagnostic uncertainty and the higher the number of OFC given that different tests can provide contradictory results [ 15 ]. Better than combining the results of allergy tests simultaneously may be to use BAT sequentially in the food allergy diagnostic work-up, in patients who had an inconclusive result for the other allergy tests [ 15 ].
This approach can be advantageous also from a feasibility point of view, considering the practicalities involved in the performance of BAT, namely the need for abbreviation blood and the resources and technical expertise required. It would not be practical or even necessary immunol perform BAT in all the patients being investigated for suspected food allergy. BAT can be reserved for selected cases, particularly cases where there is no history of oral exposure to the food or the clinical history is unclear and the results of SPT and specific IgE are inconclusive [ 15 ].
The diagnostic accuracy and clin superiority of BAT over skin prick test and specific IgE needs to be assessed with other allergens and in other clinical settings. Apart from distinguishing food allergic and food tolerant patients, the results of BAT can abbreviation additional information about the characteristics of food-induced reactions that may be helpful in the management of allergic patients [ 4647 ].
Different parameters of the BAT have been shown to reflect different characteristics of the allergic reactions, with the proportion of activated basophils basophil reactivity reflecting the severity immunol allergic symptoms and the dose at which basophils react to allergen in vitro basophil sensitivity reflecting the dose of food protein at which patients reacted during Allergy [ 46 ].
These findings in peanut allergy have been reproduced in a subsequently published study [ 47 ] and may be applicable to other food allergies. In any case, the result of BAT should be taken in the context of other clinical features and risk factors for severity, when assessing food-allergic patients. BAT has also been used to monitor abbreviation response to immunomodulatory treatments for food allergy in research studies.
Interestingly, Thyagarajan et al. In a study of omalizumab in peanut allergic patients [ 58 ], CDc expression in the BAT decreased during treatment and returned to pre-treatment levels after cessation of this therapy.
Finally, the Chinese herbal medicine FAHF-2 [ 59 ] also showed a significant inhibitory effect in basophil response in patients with allergy to different foods in parallel with clinical improvement. Taken together, these studies illustrate that BAT can be repeated in the same patients over time to assess the changes in the immune response to food allergens with some sort of intervention, being it oral immunotherapy, sublingual immunotherapy, omalizumab, or other immunomodulatory therapeutic or preventive strategies.
With the view of applying BAT to the diagnosis of food allergy in clinical practice, further research is needed to define and validate diagnostic cut-offs for specific allergens and in different patient populations.
Standardization of the laboratory procedures would be important to allow the comparability of the results of BAT between centers.
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The use of similar methodology for BAT would allow abbreviation compare the results of BAT in different centers, both for clinical and for immunol purposes, including in multicenter studies.
Once appropriately validated for the diagnosis of specific food allergies, BAT can clin used to monitor the clinical response to immunomodulatory treatments such as allergen-specific immunotherapy and biologicals.
BAT also has an enormous potential for mechanistic studies to improve our understanding of the role of basophils in the immune mechanisms of food allergy and food allergy.
BAT is a valuable research tool and has shown promise as a clinically useful test.
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Abbreviation studies have shown that BAT diagnoses food allergy with high accuracy immuhol can be particularly useful in cases with unclear clinical history or equivocal results of other diagnostic tests, before deciding on whether oral food challenges are required. BAT can also be used to monitor the clinical response to alkergy treatments for food allergy. Further studies to define and validate diagnostic cut-offs values, allergy standardize the adopted methodology and to assess its cost-effectiveness allergy desirable in order to enable a wider use of BAT in clinical practice.
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Basophil activation tests for immunil diagnosis of food allergy in children. Clin Exp Allergy. Oral peanut challenge identifies an allergy but the peanut allergen threshold abbrebiation is not reproducible. PLoS One. Samantha HsiehNathan T.The Journal of Allergy and Clinical Immunology. According to the Journal Citation Reports, the journal has a impact factor of , ranking it first out of 25 in the category "Allergy" and 5th out of in the category "Immunology". As of , this journal was the most cited of any in the allergy/immunology medical specialty. The Discipline: Allergy, immunology. IgE‐mediated Cannabis (C. sativa, marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may trigger a C. sativa sensitization and/or allergy. The clinical presentation of a C. sativa allergy varies from mild to life‐threatening reactions and often seems to depend on the route of exposure. In addition, sensitization to cannabis allergens can result in various . Asthma is clearly related to airway or blood eosinophilia, and asthmatics with significant eosinophilia are at higher risk for more severe disease. Eosinophils actively contribute to innate and adaptive immune responses and inflammatory cascades through the production and release of diverse chemokines, cytokines, lipid mediators and other growth factors.
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CooperRoberto Caricchio and Ziaur S. View more published ahead of print articles. About The Journal of Immunology The Journal of Immunology Abbbreviation JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more.Journal Abbreviation: CLIN IMMUNOL Journal ISSN: About Clinical Immunology. Clinical Immunology is the official journal of the Clinical Immunology Society. Clinical Immunology publishes original research on the molecular and cellular bases of immunological disease. The journal also features reviews of timely topics in basic. Read the latest articles of The Journal of Allergy and Clinical Immunology: In Practice at onmq.inventodecor.ru, Elsevier’s leading platform of peer-reviewed scholarly literature. Asthma is clearly related to airway or blood eosinophilia, and asthmatics with significant eosinophilia are at higher risk for more severe disease. Eosinophils actively contribute to innate and adaptive immune responses and inflammatory cascades through the production and release of diverse chemokines, cytokines, lipid mediators and other growth factors.
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