Targeting granulocyte apoptosis: mechanisms,models, and therapies

Summary: The inflammatory process is a complex series of tightly controlled cellular and biochemical events initiated by the immune system, which has evolved to eliminate or contain infectious agents and to repair damaged tissue. Apoptosis is essential for the clearance of potentially injurious inflammatory cells, such as neutrophils, eosinophils, and basophils, and the subsequent efficient resolution of inflammation. In this review, we aim to cover key features of the granulocyte life-cycle ranging from their differentiation within the bone marrow to their maturation and ultimate clearance, with a focus on granulocyte apoptosis and macrophage efferocytosis. We further aim to discuss current and emerging models of inflammation and suggest novel ways of terminating or resolving deleterious inflammatory responses with a specific view to the translation of these strategies into fully realized, pro-resolution therapies.     

A Case of Korean Ginseng-Induced Anaphylaxis Confirmed by Open Oral Challenge and Basophil Activation Test

Two case reports discussing Korean ginseng-induced allergic reactions have been published; both were inhalation-induced respiratory allergies in occupational settings. In this report we discuss the first case of anaphylaxis that developed after an oral intake of ginseng, confirmed by an open oral challenge, a skin prick test (SPT), and a basophil activation test (BAT). A 44-year-old man experienced rhinorrhea and nasal stiffness, followed by respiratory difficulty with wheeze and abdominal pain 10 minutes after oral intake of fresh ginseng. He had suffered from episodes of allergic rhinitis during the spring season for several years. Upon presentation, a physical examination, chest radiograph, and routine laboratory tests were unremarkable. Total serum IgE level was 41 IU/mL. The SPT results showed strong positive responses to alder, birch pollens, and ginseng extracts (1:500 w/v). The methacholine bronchial challenge test revealed a positive result at PC20 of 5.83 mg/mL. The open oral challenge was performed using 50 g of fresh ginseng and showed immediate onset of facial flushing, cough, respiratory difficulty with wheeze, and abdominal pain combined with a significant decrease in FEV1 levels (54% from the baseline). Serum-specific IgE and IgG4 antibodies were not detectable by enzyme-linked immunosorbent assay. BAT showed a remarkable increase in the expression of CD203c and CD63 with the addition of ginseng extract in a dose-dependent manner, while no changes were noted in the controls. In conclusion, oral intake of Korean ginseng could induce anaphylaxis, which is mediated by non-IgE-dependent direct activation of basophil/mast cells.     

Component‐resolved diagnosis from latex allergy by microarray

Background A positive specific IgE (sIgE) result for latex does not always mirror the clinical situation and is frequently found in individuals without overt latex allergy. Objective We sought to investigate the potential of component‐resolved diagnosis (CRD) of latex allergy by microarray and to assess whether the technique allows discriminating genuine allergy from asymptomatic sensitization. Methods Twenty‐six healthy controls without a history of latex allergy with a negative latex sIgE and skin test, 22 latex‐allergic patients with a compelling history of latex allergy with a positive latex sIgE and prick test and 20 latex‐sensitized individuals with a frequent asymptomatic exposure to natural rubber latex‐containing devices with a negative latex skin test but a positive sIgE were also included. CRD was performed with the ImmunoCAP ISAC microarray and traditional singleplexed ImmunoCAP. Results In all patients, the diagnosis of latex allergy could be established by the combination of recombinant latex components present on the microarray (Hev b 1, Hev b 3, Hev b 5 and Hev b 6.02). Over three‐quarters of our patients were sensitized for Hev b 5 and/or Hev b 6.02. Some patients also displayed reactivity for Hev b 1 and/or Hev b 3. In contrast, none of the individuals sensitized to natural rubber latex or control individuals demonstrated IgE reactivity for rHev b 1, rHev b 3, rHev b 5 or rHev b 6.02. Three‐quarters of the patients sensitized to latex displayed a positive microarray result for recombinant latex profilin (rHev b 8). In contrast to the results obtained by traditional ImmunoCAP for bromelain, almost no sensitization for cross‐reactive carbohydrates was demonstrated by bromelain spotted on the microarray. CRD by traditional singleplexed ImmunoCAP showed highly comparable results. Conclusion CRD by microarray is a reliable tool for diagnosing latex allergy. In addition, the technique allows discrimination between genuine allergy and sensitization. CRD by microarray can improve the diagnosis of IgE‐mediated latex allergy by discriminating between genuine allergy and sensitization. CRD by microarray is a reliable tool to diagnose latex allergy. In addition, the technique allows discrimination between a genuine allergy and simple sensitization. Cite this as: D. G. Ebo, M. M. Hagendorens, K. J. De Knop, M. M. Verweij, C. H. Bridts, L. S. De Clerck and W. J. Stevens, Clinical & Experimental Allergy, 2010 (40) 348– 358.     

Passive sensitization and histamine release of basophils

This study had two purposes. First, to examine a possible functional heterogeneity of IgE regulating basophil histamine release and the effect of using two different donor cells for passive sensitization experiments. Second, to investigate basophils not releasing histamine to anti-IgE by stimulating protein kinase C with the addition of the phorbol-ester, TPA. In consecutive experiments responding donor basophils were passively sensitized with plasma from non-responding subjects. Thus, the first set of experiments included passive sensitization of acid treated donor basophils from one atopic and one non-atopic patient with plasma from 29 children with exogenous asthma to grass pollen, cat dander, or dust mites. Different secretagogues (anti-IgE, Concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine) induced different histamine release responses due to a cellular property of the basophils not related to the type of IgE bound to the cell membrane. It was demonstrated that the allergen-induced histamine release did not depend on the extract or type of IgE when the biological activity of each extract and serum-specific IgE levels were similar. However, the atopic donor cells released significantly (P less than 0.05) more histamine than non-atopic donor cells. Thus, histamine release depends on the type of secretagogues and a cellular property which is maybe influenced by the presence of serum factors and a certain type of IgE in the serum of atopics. The second set of experiments included 10 patients (6 atopics and 4 non-atopics) with non-histamine releasing basophils. In the presence of 10 ng/ml TPA, however, seven of 10 patients released histamine at anti-IgE challenge. Three months later two additional patients became responsive in the presence of TPA. By passive sensitization of responding donor basophils the non-responding patients were shown to possess functionally intact IgE. Thus, the discrepancies sometimes observed between clinical symptoms, serological IgE-antibody measurements and histamine release testing in allergic patients may be related to a cellular property of basophils.     

Basophils as critical orchestrators of Th2-type immune responses

Basophils are relatively rare leukocytes that potentially play a role in both systemic anaphylaxis and, owing to their ability to migrate from the blood into various other tissues, in more localized aspects of allergic inflammation. Given their greater sensitivities to allergen provocation compared with their tissue-fixed mast cell counterparts, and by virtue of their capacity to more readily generate Th2-type cytokines, basophils have been considered to play more than a bystander role in initiating and maintaining allergic disorders. However, only very recently has clearer evidence shed light on the abilities of this cell type to orchestrate chronic allergic inflammation and promote Th2 immunity in the early induction stages of allergy. This review summarizes these recent advances in understanding the role of basophils in orchestrating and maintaining allergic responses.     

过敏性输血反应的原因分析及检测方法

<正>免疫相关非溶血性输血反应包括过敏反应、发热反应、输血后紫癜、输血相关移植物抗宿主病,输血相关急性肺损伤等。其中过敏反应发生率在近年来国内外报道中均高于其他种类输血反应。输血相关过敏反应(allergic transfusion reactions,ATRs)的临床表现症状有:荨麻疹、瘙痒、皮肤红斑、潮红、血管性水肿、支气管痉挛、肺水肿、血压下降以及过敏性休克等,一些症状主要累及局部组织器官发生过敏性炎症,药物治疗有效,但也会存在