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Abstract Allergic rhinitis (AR) affects 23–30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontrolled. Allergen immunotherapy (AIT) has been shown to improve the level of control up to 84% of patients being controlled by AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products for AIT in patients who are allergic to airborne allergens. AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues of each of the single products but also by several patient- and physician-related factors. Patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT. Physicians dealing with AR patients should inform patients on tolerance-inducing effects of AIT and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium.

Generally, terrestrial laser scanning surveys involve a rather large number of scans to ensure a high percentage of overlap required for the scan registration phase (target-based or point-based registration, cloud-to-cloud registration). These approaches result in data redundancy that could slow down both the acquisition and post-processing phases. In recent years, the technological evolution in the field of laser scanners has been directed to the development of devices that are able to perform an onsite pre-registration, to optimize the survey procedures and the reliability of the registration of the scan. The paper presents the results achieved during a terrestrial laser scanning survey carried out for the documentation and 3D reconstruction of the large and complex archaeological remains of the so-called Roman Domus in the archaeological site of Lylibaeum (Marsala, Italy). The survey was also conducted using a terrestrial laser scanner capable of pre-registering scans using a topographic approach. The pre-registration procedure and the data acquisition strategy have allowed to optimize the workflow and to obtain a 3D model of the Roman Domus with a high level of detail and area coverage.

Collecting information and mapping are fundamental aspects of systematic archaeological excavation, documentation and interpretation. The process of recording physical evidence is the first step in the archaeological study with the goal to derive spatial and semantic information from the gathered and available data. Archaeological reports always include 2D maps, sections, data distribution and other spatial data. Indeed, the representation is inseparable from the archaeological practice, but this is undoubtedly a time-consuming activity. Nowadays, archaeologists can take advantages of various recording techniques to produce highly accurate 3D models and ortho-images of archaeological sites. Far from replacing the more traditional techniques, the development of new geomatics techniques tries to answer, in a more efficient way, to the needs of archaeological research. The use of Unmanned Aerial Vehicles (UAVs) has become more popular in archaeological excavations. In particular, UAV systems become a useful, versatile and cost-effective approach to record large archaeological areas in order to measure and completely document them. They are the fastest way to produce high-resolution 3D models of entire sites and allow archaeologists to collect accurate spatial data that can be used for spatial analyses using GIS platform. The paper presents the results of several UAV surveys of the archaeological remains of Lilybaeum, the ancient city of Marsala (Southern Italy), performed in the Archaeological Park of “Lilibeo”. The UAV acquisitions were planned and carried out to complete the previous traditional documentation of the site. Very detailed 3D models and high-resolution ortho-images, together with some new field campaigns, have been used for new analysis and documentation of the site and for the realization of the archaeological map of Lilybaeum.

The task of documentation and conservation of Cultural Heritage defines the challenges that geomatics techniques have to overtake in order to provide different solutions that combine the automation of processes with accurate results. The employment of integrated technologies allows improving the documentation of Cultural Heritage from a quantitative and qualitative point of view. The use of range and image-based techniques ensures the possibility to completely record articulated structures such as building with underground environments. The latter present often problematic survey conditions that imposed well planned and appropriate solutions. In this context, the paper presents the results of a 3D survey of the underground “Sybil hypogeum” and the related overhead church located in the Archaeological Park of Lilibeo (Marsala, Southern Italy). An integrated survey was planned in order to combine laser scanning technology with terrestrial-based and Unmanned Aerial Vehicle (UAV)-based photogrammetry to acquire the three-dimensional data of the whole complex (underground environments and overhead church). The aims of the work are related to test a topographic approach by a traverse method for scans registration and to archive a complete and detailed 3D model of the whole area. This model could be used to prevent the risk of information’s loss and to improve the knowledge of the site.

The survey of archaeological sites by appropriate geomatics technologies is an important research topic. In particular, the 3D survey by terrestrial laser scanning has become a common practice for 3D archaeological data collection. Even if terrestrial laser scanning survey is quite well established, due to the complexity of the most archaeological contexts, many issues can arise and make the survey more difficult. The aim of this work is to describe the methodology chosen for a terrestrial laser scanning survey in a complex archaeological environment according to the issues related to the particular structure of the site. The developed approach was used for the terrestrial laser scanning survey and documentation of a part of the archaeological site of Elaiussa Sebaste in Turkey. The proposed technical solutions have allowed providing an accurate and detailed 3D dataset of the study area. In addition, further products useful for archaeological analysis were also obtained from the 3D dataset of the study area.

The photogrammetric survey of architectural Cultural Heritage is a very useful and standard process in order to obtain accurate 3D data for the documentation and visualization of historical buildings. In particular, the integration of terrestrial close-range photogrammetry and Remotely Piloted Aircraft Systems (RPASs) photogrammetry allows to create accurate and reliable 3D models of buildings and to monitor their state of conservation. The use of RPASs has indeed become more popular in Cultural Heritage survey to measure and detect areas that cannot normally be covered using terrestrial photogrammetry or terrestrial laser scanner. The paper presents the results of a photogrammetric survey executed to document the monumental complex of Villa Lampedusa ai Colli in Palermo (Italy), one of the most important historical buildings of the town. An integrated survey by close-range photogrammetry and RPAS photogrammetry was planned and carried out to reconstruct the 3D digital model of the monumental complex. Different images configurations (terrestrial, aerial nadiral, aerial parallel and oblique to the façades) have been acquired; data have been processed to verify the accuracy of the photogrammetric survey as regards the camera calibration parameters and the number of Ground Control Points (GCPs) measured on building façades. A very detailed 3D digital model and high-resolution ortho-images of the façades were obtained in order to carry out further analysis for historical studies, conservation and restoration project. The final 3D model of Villa Lampedusa ai Colli has been compared with a laser scanner 3D model to evaluate the quality of the photogrammetric approach. Beyond a purely metric assessment, 3D textured model has employed to generate 2D representations, useful for documentation purpose and to highlight the most significant damaged areas. 3D digital models and 2D representations can effectively contribute to monitor the state of conservation of historical buildings and become a very useful support for preliminary restoration works.

The VAST (valorisation of history and landscape) project (http://vast.fbk.eu/) was part of the initiatives promoted by the Autonomous Province of Trento (Italy) for the commemoration of the 100th Anniversary of the First World War (WWI) outbreak. The project was primarily aimed to document and promote, through 3D digitization approaches and communication material, the memory of sites, theatre of the world conflict. The Italian Trento’s province had been under the Austro–Hungarian Empire until the end of the WWI, during which represented a crucial and bloody war front between the Austrian and Italian territories. The region was constellated of military fortresses, trenches and tunnels, most of them now ruined and at risk to slowly disappear. 3D surveying and modelling techniques have been exploited to produce 3D digital models of structures and objects, along with virtual tours, communication material and a WebGIS of the area. All the products are available on the web for valorisation, educational and communication purposes.

Nowadays, 3D documentation of architectural assets is becoming a demanding task for the valorisation of Cultural Heritage especially after a restoration project. The 3D documentation can be used for detailed analysis of specific elements, for monitoring the state of conservation and for valorisation actions. The paper describes the results of the 3D close-range photogrammetry survey of the main portal of the Cathedral of Monreale (Palermo, Italy). The Cathedral is one the most important monumental complexes in Sicily that, for its high historical and artistic importance has been inscribed on UNESCO’s World Heritage List since 2015. The main portal of the Cathedral has been recently restored. The restoration work has given the opportunity to evidence small details of the sculptural decorations and to carry out new interpretative analysis of the bas-reliefs. The main purpose of the work is to obtain a detailed 3D model and a high-resolution ortophoto of the entire portal and of some architectural details. The study was used to evaluate the most appropriate technical solutions for the 3D survey and to define the most suitable parameters for image acquisition and data processing.

The paper presents a digital approach to the reconstruction and analysis of two small-sized fragments of louteria, a kind of large terracotta vase, found during an archaeological survey in the south of Sicily (Italy), in the area of Cignana near the Greek colony of Akragas (nowadays Agrigento). The fragments of louteria have been studied by an image-based approach in order to achieve high accurate and very detailed 3D models. The 3D models have been used to carry out interpretive and geometric analysis from an archaeological point of view. Using different digital tools, it was possible to highlight some fine details of the louteria decorations and to better understand the characteristics of the two fragments. The 3D models provide also the possibility to study and to document these archaeological finds in a digital environment.

Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet the consensus formula (i.e., an increase of 20% + 2). The upper limit of normal determined by the manufacturer is 11.4 ng/mL; however, this boundary has been the subject of debate. According to ECNM and AIM experts, the normal range of baseline tryptase should be 1 to 15 ng/mL. A genetic trait, hereditary alpha tryptasemia, characterized by an increased alpha coding TPSAB1 copy number is associated with a baseline value above 8 ng/mL. Elevated tryptase can also be found in chronic kidney disease, obesity, and hematological neoplasms. A tryptase > 20 ng/mL serves as a minor criterion to diagnose systemic mastocytosis and an increase in tryptase > 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome. The goal of this review is to demonstrate the (in)significance of tryptase using some clinical vignettes and to provide a practical guide on how to manage and interpret an elevated tryptase level.

Mastocytosis is a complex heterogenous multisystem disorder that is characterized by pathologic activation or accumulation of neoplastic mast cells (MCs) in one or more organs. This clonal MC expansion is often associated with a somatic gain-of-function mutation (D816V in most of the cases) in the KIT gene, encoding for the MC surface receptor KIT (CD117), a stem cell growth factor receptor. Based on clinical and biochemical criteria, the World Health Organization (WHO) divided mastocytosis into different subclasses. The exact prevalence of mastocytosis remains elusive, but it is estimated that the disease affects approximately 1 in 10,000 persons. The clinical presentation of mastocytosis varies significantly, ranging from asymptomatic patients to a life-threatening disease with multiple organ involvement, potentially leading to cytopenia, malabsorption, hepatosplenomegaly, lymphadenopathy, ascites or osteolytic bone lesions with pathological fractures. Patients with mastocytosis may experience symptoms related to release of MC mediators, such as flushing or diarrhea or even more severe symptoms such as anaphylaxis. Recently, a new genetic trait, hereditary alpha tryptasemia (HaT), was described which involves a copy number variation in the TPSAB1-gene. Its role as standalone multisystem syndrome is heavily debated. There is emerging evidence suggesting there might be a link between HaT and due to the increased prevalence of HaT in patients with SM. The aim of this review is to provide a practical roadmap for diagnosis and management of mastocytosis and its associated entities, since there are still many misconceptions about these topics. Abbreviations: AdvSM: Advanced systemic mastocytosis; ASM: Aggressive systemic mastocytosis; aST: acute serum tryptase; BM: Bone marrow; BMM: Bone marrow mastocytosis; bST: baseline serum tryptase; CM: Cutaneous mastocytosis; DCM: Diffuse cutaneous mastocytosis; HVA: Hymenoptera venom allergy; HaT: Hereditary alpha tryptasemia; ISM: Indolent systemic mastocytosis; MC: Mast cell; MCA: Mast cell activation; MCAS: Mast cell activation syndrome; MCL: Mast cell leukemia; MIS: Mastocytosis in the skin; MMAS: Monoclonal mast cell activation syndrome; MPCM: Maculopapular cutaneous mastocytosis; SM: Systemic mastocytosis; SM-AHN: Systemic mastocytosis with associated hematological neoplasm; SSM: Smouldering systemic mastocytosis; VIT: Venom immunotherapy.

Background: Immediate hypersensitivity reactions to penicillins are often labeled on the basis of a similar set of symptoms, but a key feature of these reactions that can be reproduced in diagnostic testing may be the timing of a reaction in relation to the dose administration., Objective: To determine whether the timing of a reaction in response to the last dose of a penicillin would predict the results of diagnostic testing., Methods: We evaluated 1074 patients by performing skin tests, serum specific IgE assays (ImmunoCAP), and challenges. Patients who were evaluated by us more than 6 months after their reactions and found negative were reevaluated within 2 to 4 weeks., Results: Patients who had reacted within 1 hour after the first dose, within 1 hour after subsequent doses, more than 1 hour to within 6 hours after the first dose, or more than 1 hour to within 6 hours after subsequent doses were classified as group A (758 individuals), B (92), C (67), or D (157), respectively. Penicillin hypersensitivity was diagnosed in 707 patients (65.8%) by skin tests (407 patients, 57.6%), ImmunoCAP (47, 6.6%), both tests (232, 32.8%), or challenges (21, 3%). A conversion to allergy-test positivity occurred in 7 of 10 patients with anaphylactic reactions and in 1 of 28 patients with other reactions who were reevaluated after negative challenges. The rate of penicillin-allergic patients in groups A, B, C, and D was 85%, 35.9%, 35.8%, and 3.8%, respectively. Only 1 of 107 patients reporting cutaneous reactions lasting more than 1 day had positive results to allergy tests., Conclusions: IgE-mediated hypersensitivity can be diagnosed by skin tests in about 70% of subjects who react within 1 hour (eg, patients from groups A and B). This hypersensitivity can be lost over time, as demonstrated by the negativization of allergy tests in follow-up studies. In subjects with anaphylactic reactions, however, it is advisable to not consider this phenomenon definitive. In fact, a conversion to allergy test positivity can be observed in up to 20% of such subjects retested after negative challenges., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro . It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen., (© 2019 The Authors.)

Objectives: Cannabis allergy has mainly been described following recreational use but some cases also point to cannabis sensitisation as a result of occupational exposure. As a consequence, little is known on the prevalence and clinical phenotype of occupational cannabis allergy. Therefore, this study aims to explore the allergy-associated health risks of occupational cannabis exposure in Belgian police force personnel., Methods: 81 participants, active in the police force, reporting regular occupational cannabis exposure during the past 12 months, were included. History was combined with a standardised questionnaire on allergies and cannabis exposure.Basophil activation tests (BATs) with a crude cannabis extract and rCan s 3 were performed. In addition, specific (s)IgE rCan s 3 as well as sIgE to house dust mite, six pollen and three mould allergens were quantified., Results: Although 42% of the participants reported respiratory and/or cutaneous symptoms on occupational cannabis exposure, all cannabis diagnostics were entirely negative, except one symptomatic case demonstrating a borderline result. Furthermore, there is no significant difference between the groups with and without symptoms on cannabis exposure in terms of allergenic sensitisations., Conclusions: The origins of the reported respiratory and cutaneous symptoms during cannabis exposure remain elusive but are probably due to non-immune reactions. It should be noted that the study was volunteer-based possibly reflecting an excessive number of symptomatic individuals. Nevertheless, as only one participant reported using fully protective gear, much improvement is needed for reducing the number of symptoms reported on duty, independent of their origin., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

During sepsis, disturbed gastrointestinal motility and increased mucosal permeability can aggravate sepsis due to the increased risk of bacterial translocation. To help identify new therapeutic targets, there is a need for animal models that mimic the immunological changes in the gastrointestinal tract as observed during human sepsis. We therefore characterized in detail the gastrointestinal neuroimmune environment in the cecal ligation and puncture (CLP) model, which is the gold standard animal model of microbial sepsis. Mice were sacrificed at day 2 and day 7, during which gastrointestinal motility was assessed and cytokines were measured in the serum and the colon. In the spleen, lymph nodes, ileum, and colon, subsets of leukocyte populations were identified by flow cytometry. Septic animals displayed an impaired gastrointestinal motility at day 2 and day 7. Two days post-CLP, increased serum and colonic levels of proinflammatory cytokines were measured. Flow cytometry revealed an influx of neutrophils in the colon and ileum, increased numbers of macrophages in the spleen and mesenteric lymph nodes, and an enhanced number of mast cells in all tissues. At day 7 post-CLP, lymphocyte depletion was observed in all tissues coinciding with increased IL-10 and TGF- β levels, as well as increased colonic levels of IL-17A and IFN- γ . Thus, CLP-induced sepsis in mice results in simultaneous activation of pro- and anti-inflammatory players at day 2 and day 7 in different tissues, mimicking human sepsis.

We present the case of a 39-year-old man with a severe glottis stenosis. The saddle nose, images of laryngotracheal stenosis and the (FDG) positron-emission tomography/computed tomography lead to a final diagnosis of relapsing polychondritis. In the patient a coexistent myelodysplastic syndrome was diagnosed. Moreover, the elevated total IgG4 exceeding 135 ml/dl requested additional immunochemistry for detection of IgG4-bearing plasma cells in the biopsies. The patient underwent an allogenic stem cell transplantation and died on day 40 after the transplantation because of an acute steroid-resistent graft vs host.

Background and Aims: Inflammatory mediators that cross-talk in different metabolically active organs are thought to play a crucial role in the pathogenesis of Nonalcoholic Steatohepatitis (NASH). This study was aimed at investigating the CD4+RORγt+ T-helper cells and their counterpart, the CD4+CD25+FOXP3+ regulatory T cells in the liver, subcutaneous adipose tissue (SAT), and abdominal adipose tissue (AAT) in a high fat diet (HFD) mouse model., Methods: C57BL6 mice were fed a HFD or a normal diet (ND). Liver enzymes, metabolic parameters, and liver histology were assessed. The expression of CD4+RORγt+ cells and regulatory T cells in different organs (blood, liver, AAT, and SAT) were analyzed by flow cytometry. Cytokine and adipokine tissue expression were studied by RT-PCR., Results: Mice fed a HFD developed NASH and metabolic alterations compared to normal diet. CD4+RORγt++ cells were significantly increased in the liver and the AAT while an increase of regulatory T cells was observed in the SAT of mice fed HFD compared to ND. Inflammatory cytokines were also upregulated., Conclusions: CD4+RORγt++ cells and regulatory T cells are altered in NASH with a site-specific pattern and correlate with the severity of the disease. These site-specific differences are associated with increased cytokine expression.

Allergic reactions in the parturient are challenging for the anaesthetist who is dealing with both mother and baby, often in circumstances when there is a need for delivery. While most previous reviews have focused on specific substances in individual cases, this review focuses on allergic reactions during the peripartum period, the differential diagnosis and specific treatment options. Immunoregulation and susceptibility to allergic reactions may change during pregnancy. Compared with non-pregnant patients, in whom neuromuscular blocking drugs are the most common triggering substances, allergic reactions in parturients mostly occur following contact with latex, injection of antibiotics and uterotonics, and infusion of colloids. With the exception of latex, where patient history may raise suspicion, allergic reactions may occur without prior exposure to triggering agents. Most drugs used for resuscitation of the non-pregnant patient are suitable for the parturient. Some substances, such as H2-receptor antagonists for aspiration prophylaxis or corticosteroids for prematurity, may have been given before the event. Although fetal outcome is important, the mother is the primary focus of care., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Immunoglubulin E antibody-mediated allergic reactions to opioids are rare and difficult to document correctly., Objective: Assessment of the basophil activation test in the diagnosis of IgE-mediated allergy to the antitussive pholcodine and associated sensitizations to neuromuscular blocking agents (NMBA)., Methods: Three patients with a suspected IgE-mediated allergy to pholcodine were investigated using skin tests, quantification of specific IgE, and flow cytometric activation of basophils., Results and Conclusion: Flow cytometric activation of basophils, with simultaneous analysis of CD63 appearance and median histamine content per cell, is the only technique capable to correctly document pholcodine allergy. The negative predictive value of basophil activation tests might help to elucidate on the controversial putative cross-reactivity between pholcodine and NMBA., (Copyright © 2013 International Clinical Cytometry Society.)

Hypersensitivity to iodinated radiologic contrast media occurs in 1-3% of patients. A complete allergological work-up requires the identification of the pathogenetic mechanism as well as the identification of safe alternatives. The current diagnostic approach relies upon skin tests, since no other in vitro test is standardized. However skin tests do not have an absolute predictive value, cannot be executed immediately and may expose the patients to the risk of severe reactions. Recently the flow-cytometric evaluation of activated basophils, also known as basophil activation test (BAT) has been introduced. Our case report of a 28-year old female who experienced an anaphylactic shock immediately after administration of iomeprol supports the role of BAT in the diagnosis and management of hypersensitivity reactions to contrast media. The possibility of shortening the diagnostic work-up without endangering the health of patients represents the main advantage of this test.

Food allergy, an abnormal immunological response due to sensitization to a food component, has become an important health problem, especially in industrialized countries. The aim of this study was to investigate the impact of thermal processing and glycation on the basophil activation by hazelnut proteins using a basophil activation test. Patients with systemic allergic reactions (SR; n=6) to hazelnut as well as patients with an isolated oral allergy syndrome (OAS; n=4) were investigated. Thermal processing of hazelnut proteins either in the presence or absence of wheat proteins did not result in major changes in the stimulatory activity of the basophils for patients with SR or OAS. For the patients with OAS, incubation of hazelnut proteins with glucose led to complete depletion of the stimulatory activity of the basophils. An increase in stimulatory activity of the basophils for two out of six patients with SR was observed. For the other four patients slight or complete abolition of the stimulatory activity was observed. These results indicate that some patients with SR to hazelnut are at risk when exposed to hazelnut proteins, even in processed foods., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Major histocompatibility complex (MHC) class II tetramers (tetramers) allow to detect allergen-specific CD4(+) T cells at a single-cell level. Limits to this technology include HLA restriction and the need to identify immunodominant T cell epitopes., Objective: Assessing the expression of various activation markers following allergen stimulation to replace tetramer staining., Methods: Peripheral blood mononuclear cells (PBMCs) from 25 birch pollen, grass pollen or house dust mite allergic individuals were stimulated with peptide mixes encompassing immunodominant epitopes from corresponding major allergens. After 2 weeks of in vitro amplification, cells were stained with both the appropriate tetramer and antibodies directed to CD25, CD30, CD39, CD69, CD137, CD154, GITR, HLA-DR and ICOS, before FACS analysis., Results: Following allergen stimulation, percentages of tetramer(+) cells among CD4(+) CD154(+) cells range from 5% to 87%, depending upon donors. As for CD154, a large inter-individual variability is observed in terms of surface expression for all activation markers tested in allergen-stimulated PBMCs. T cells reactive with either tetramers (0.4-10.4% CD4(+) T cells) or anti-marker antibodies (2.2-32.7% CD4(+) T cells), but not both, are observed, reflecting the presence of anergic as well as non-specifically activated cells. Tetramer(+) /marker(+) , tetramer(+) /marker(-) and tetramer(-) /marker(+) cells were compared for their capacity to express cytokines, demonstrating that only the former represent bona fide allergen-specific activated CD4(+) T cells, based upon a higher expression of cytokines or corresponding genes in presence of the allergen., Conclusion and Clinical Relevance: No strict correlation exists between tetramer staining and the expression of multiple activation markers in stimulated CD4(+) T cells. Dual staining allows to discriminate functional tetramer(+) /marker(+) vs. anergic (tetramer(+) /marker(-) ) allergen-specific T cells or non-specifically activated (tetramer(-) /marker(+) ) T cells. Combining tetramer staining with the detection of activation markers helps understanding patient heterogeneity regarding specific CD4(+) T cell responses. This approach has immediate relevance for monitoring immune changes induced during specific immunotherapy., (© 2011 Blackwell Publishing Ltd.)

Background: A better understanding of allergen-specific CD4(+) T cell responses is needed to help improving immunological therapies. Objective To compare CD4(+) T cell responses against seasonal (Bet v 1) and perennial (Der p 1, Der p 2) allergens., Methods: Major histocompatibility complex class II peptide tetramers were engineered to monitor allergen-specific T cell responses. After in vitro expansion, tetramer(+) cells were tested for surface markers using cytofluorometry. Cytokine gene expression and production were assessed using quantitative PCR and cytokine surface capture assays, respectively., Results: Tetramer(+) cells were detected in 19 patients allergic to house dust mites (HDM), seven allergic to birch pollen, 13 allergic to both and nine non-allergics with either an HLA-DRB1(*) 0101, (*) 0301, (*) 1501 or an HLA-DPB1(*) 0401 background. High-avidity T cells are elicited against the immunodominant Bet v 1(141-155) epitope, whereas broader low-avidity T cell responses are induced against Der p 1(16-30) ,(110-124) ,(171-185) and Der p 2(26-40,107-121) epitopes. Responses against Bet v 1 involve effector (CDL62 low, CCR7 low) or central (CD62L(+) , CCR7(+) ) memory cells in allergic and non-allergic individuals, respectively, whereas central memory cells are mostly detected against mite allergens. In non-allergics, both mite and Bet v 1-specific T cells produce IFN-γ and IL-10. In contrast to Bet v 1-driven Th2 responses, mite allergens induce highly polymorphic responses in allergics, including Th1, Th2/Th17 or mixed Th1/Th2 profiles. Mite-specific T cell frequencies in the blood remain in the range of 1-6 × 10(-4) CD4(+) T cells throughout the year., Conclusion: Different memory CD4(+) T cell responses are elicited in the context of chronic vs. seasonal stimulation with the allergen(s). The heterogeneity in the patterns of CD4(+) T cell responses observed in patients allergic to HDMs should be taken into account for specific immunotherapy., (© 2010 Blackwell Publishing Ltd.)

In 2008, many thousands of articles were published on the subject of allergic disease with over 200 reviews, editorials and original papers in Clinical & Experimental Allergy alone. These represent a considerable amount of data and even the most avid reader could only hope to assimilate a small fraction of this knowledge. There is therefore a pressing need for the key messages that emerge from a journal such as Clinical & Experimental Allergy to be summarized by experts in the field in a form that highlights the significance of the developments and sets them in the context of important findings in the field published in other journals. This also has the advantage of making connections between new data in conditions such as asthma, where articles often appear in different sections of the journal. As can be seen from this review, the body of work is diverse both in terms of the disease of interest and the discipline that has been used to investigate it. However, taken as a whole, we hope that the reader will gain a flavour of where the field is mature, where there remain controversies and where the cutting edge is leading.

In this study, we used HLA-DRB1*0101, DRB1*0401, and DRB1*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4(+) T cell responses against the immunodominant T cell epitope (peptide 141-155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals. We could detect Bet v 1-specific T cells in the PBMC of 20 birch pollen allergic patients, but also in 9 of 9 healthy individuals tested. Analysis at a single-cell level revealed that allergen-specific CD4(+) T cells from healthy individuals secrete IFN-gamma and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-gamma), as corroborated by patterns of cytokines produced by T cell clones. A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells. In this model of seasonal exposure to allergen, we also demonstrate the tremendous dynamics of T cell responses in both allergic and nonallergic individuals during the peak pollen season, with an expansion of Bet v 1-specific precursors from 10(-6) to 10(-3) among circulating CD4(+) T lymphocytes. Allergy vaccines should be designed to recapitulate such naturally protective Th1/regulatory T cell responses observed in healthy individuals.

Background: We report herein critical methodological principles for assessing, at a single cell level, allergen-specific T cell responses using MHC class II peptide tetramers., Methods: We developed MHC class II peptide tetramers to monitor T cell responses against the immunodominant Bet v 1(141-155) peptide in individuals with either an HLA-DRB1*0101, DRB1*0401 or DRB1*1501 background. In vitro stimulation was performed with serially truncated versions of the Bet v 1(141-155) epitope chemically conjugated to the Ii-Key peptide., Results: Identification of Bet v 1(141-155) as a high-affinity epitope for multiple HLA-DRB1 allotypes led to the development of corresponding tetramers detecting Bet v 1(141-155)-specific T cells with a high specificity and sensitivity. Stimulation with Bet v 1(141-155) Ii-Key conjugate peptides is the most efficient procedure to expand Bet v 1(141-155)-specific CD4+ T cells, allowing to detect such cells in both allergic and healthy individuals. MHC class II Bet v 1(141-155) tetramer-positive T cells produce IFN-gamma and IL-10 in healthy individuals, and IL-5 in allergic patients. Frequencies of Bet v 1-specific CD4+ T cells circulating in the blood of allergic or nonallergic individuals range from approximately 10(-5) to 10(-3) CD4+ T cells, outside or within the pollen season, respectively., Conclusions: MHC class II peptide tetramers are valuable tools to assess allergen-specific T cell responses, both qualitatively and quantitatively. Selection of a high-affinity T cell epitope, as well as optimization of in vitro stimulation conditions to expand rare T cell progenitors are critical success factors in those analyses., ((c) 2008 S. Karger AG, Basel.)

A patient with increasing dysphagia due to external bone compression of the oesophagus is presented. Radiographic evaluation revealed the underlying condition to be a diffuse idiopathic skeletal hyperostosis with exuberant and bumpy change within the anterior longitudinal ligament.

We present the case of a 69 yr old, white male, suffering from diffuse interstitial lung disease, finally diagnosed as paracoccidioidomycosis or South American blastomycosis. During the course of his disease, antineutrophil cytoplasmic antibodies (c-ANCAs) became positive, suggesting the possibility of a Wegener's granulomatosis. Transbronchial biopsies and a video-assisted thoracoscopic lung biopsy revealed only the pulmonary yeast infection, without other co-existing pathology. During treatment with itraconazole, the patient improved clinically and functionally, and c-ANCAs became negative. Serological monitoring confirmed the diagnosis. To our knowledge, this is the first report describing positive c-ANCAs in a patient with paracoccidioidomycosis. It re-emphasizes the fact that cautious interpretation of c-ANCAs in patients without convincing clinical signs or pathological evidence of a granulomatous vasculitis is absolutely necessary. In this era of increased mobility, a thorough medical history, including documentation of travel, remains an inexpensive tool in making a diagnosis and is still the cornerstone of good medical practice.

CD5+ and CD23+ lymphocytes were determined in peripheral blood of patients with rheumatoid arthritis (RA) (n = 56), systemic lupus erythematosus (SLE) (n = 20) and primary Sjögren's syndrome (pSS) (n = 21). No definite correlation between the numbers of CD5+ or CD23+ cells and most of the parameters of disease activity was found. A significant correlation (r = 0.59, p = 0.005) between rheumatoid factor levels and numbers of CD23+ cells was found in RA patients not taking disease modifying agents. For SLE and pSS no signification associations with autoantibody production were found. In conclusion, although CD5+ and CD23+ B cells might be important in the pathogenesis of autoimmune diseases, determination of these subsets in peripheral blood of RA, SLE or pSS patients provides no clear useful clinical information for the individual patient.

The "large cell anaplastic lymphoma, Ki-1 positive" is a recently described lymphoma subtype (about 1-8% of all NHL). Distinction from Hodgkin's disease and true histiocytic lymphoma/malignant histiocytosis is not always possible, even by experienced pathologists. It was recently incorporated in the updated Kiel Classification of lymphomas. Classical histologic appearance is a sinusoidal growth pattern in lymph nodes and presence of large bizarre anaplastic cells. Use of cell markers LCA, EMA and Ki-1 or Ber-H2 is essential for diagnosis. The mean age of patients is 50 years. Approximately 50% of patients have an advanced stage (III-IV). Prognosis depends on age and tumor localisations. Cutaneous involvement only is usually associated with a good prognosis. Median survival for patients with extra-cutaneous disease is 13 months. Treatment with intensive chemotherapy is usually needed. Long term remissions are more frequently seen in children and adolescents.