Isolation and characterization of salivary antigens from the female tick, Dermacentor andersoni

The salivary glands of ixodid ticks are complex organs which are known to contain the antigens responsible for tick resistance in animals. We have identified a large number of proteins from salivary gland extracts (SGE), at least some of which are immunologically recognized by tick resistant animals and which are therefore presumed to be secreted salivary components. During the 6 to 10 day feeding process, a number of these antigens alter in concentration according to individual kinetics, and some of these changes correlate with the kinetics of skin test reactivity of SGE obtained at different times throughout the feeding period. By use of immunoaffinity chromatography we have isolated large quantities of many of the salivary antigens (SGA) contained in SGE, and found that they contain several esterase activities. SGA stimulates both immediate and delayed skin reactions in tick resistant guinea-pigs, and these reactions are about 200-fold more intense, per unit protein, than those elicited by SGE. The skin reactions to SGA are basophil-mediated and have many features in common with the cutaneous basophil hypersensitivity reactions of tick resistant animals. The demonstrated antigenic complexity of the glands may have profound implications for attempts to develop anti-tick vaccines, as it may eventually be found that candidate vaccines will have to incorporate more than one tick antigen in order to be effective.     

Total absence of eosinophils in a patient with chronic urticaria and vitiligo

A 71-year-old woman with chronic urticaria and vitiligo is reported who lacked eosinophil and basophil leukocytes in her blood, bone-marrow and skin. No IgE was detectable in serum. She had a low level of serum eosinophil cationic protein (ECP) which could indicate that some eosinophils had been formed but rapidly destroyed. There was, however, no ECP release when the patient's serum was mixed with heterologous eosinophils. Staining for eosinophilic proteins in white blood cells by monoclonal antibodies revealed no storage or secreted forms of ECP. The source of ECP in our patient therefore remains unknown.     

Two new types of allergens from the cockroach,Periplaneta americana

Periplaneta americana cockroach is an important source of inhalant indoor allergen resource, and there are more than twenty IgE‐binding components identified in P. americana, but only nine allergens were characterized. Our knowledge about cockroach allergens remains poor. In this work, two novel allergen proteins Per a 11 (alpha‐amylase) and Per a 12 (chitinase) with molecular weight around 55 and 45 kDa, respectively, were purified and characterized from the midgut of cockroaches. Their primary sequences were determined by Edman degradation, mass spectrometry, and cDNA cloning. Sera from 39 and 30 of 47 (83.0% and 63.8%) patients reacted to Per a 11 and Per a 12 on immunoblots, respectively. The allergenicity of Per a 11 and Per a 12 was further confirmed by competitive ELISA, basophil activation test (BAT), and skin prick test (SPT). They appear to be of importance for the allergic reactions induced by cockroach and have a potential for component‐based diagnosis of allergy.     

Soluble ST2 suppresses IL-5 production by human basophilic KU812 cells,induced by epithelial cell-derived IL-33

Background

Epithelial cell-derived IL-33 has an important role in the initiation and activation of innate allergic inflammation. IL-33 acts as a cytokine through the ST2 receptor (ST2L) and it stimulates the production of Th2 cytokines. Soluble ST2 (sST2) may regulate Th2 responses by neutralizing the activity of IL-33. Basophils express ST2L and produce IL-5 in response to IL-33. However, the role of the epithelial cell–basophil interaction and sST2 in IL-5 production remains unclear.

Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA2LEN project

The synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (FcepsilonRI) and other factors regulating the activation of FcepsilonRI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper.     

Beef-Induced Anaphylaxis Confirmed by the Basophil Activation Test

Beef allergies are relatively rare, especially in adults. However, clinical manifestations can vary from urticaria, angioedema, anaphylaxis to gastrointestinal symptoms. Currently available tests, such as skin testing or in vitro determination of beef-specific immunoglobulin E (IgE), do not provide an accurate diagnosis of beef allergy. The recent development of the basophil activation test (BAT) presents a new opportunity for the diagnosis of food allergies. Here, we report a 37-year-old woman with a history of recurrent generalised urticaria, nausea, vomiting and hypotension after ingestion of beef, suggesting a beef allergy. Although the skin prick test and serum specific IgE to beef, pork and milk allergens showed negative results using commercial kits, the BAT showed significant upregulation of CD203c in a dose-dependent manner compared to both non-atopic and atopic controls. To our knowledge, this is the first case study of beef allergy consisting of a non-IgE-mediated reaction. The detection of food allergies using direct basophil activation is suggested to complement conventional diagnostic tests.     

Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving inflammation of the joints. Among the autoantibodies described in RA, anticitrullinated protein antibodies (ACPAs) are highly specific and predictive for RA. In addition, ACPAs have been implicated in the pathogenesis of RA. However, a direct functional response of immune cells from ACPA⁺ RA patients toward citrullinated proteins has not been demonstrated. In this study, we show that exposure to citrullinated antigens leads to activation of basophils from ACPA⁺ RA patients within 20 minutes. This was not observed after exposure of basophils to noncitrullinated control antigens or after stimulation of basophils from ACPA⁻ RA patients and healthy controls. Basophil activation was correlated with the binding of citrullinated proteins to basophils. Furthermore, serum from ACPA⁺ RA patients in contrast to that from ACPA⁻ RA patients could specifically sensitize human FcεRI expressing rat basophil cells (RBL), enabling activation by citrullinated proteins. Mast cell degranulation products such as histamine levels were enhanced in synovial fluid of ACPA⁺ RA patients as compared with ACPA⁻ RA and osteoarthritis patients. In addition, histamine levels in synovial fluid from ACPA⁺ RA patients correlated with IgE levels, suggesting degranulation of mast cells by cross-linking IgE. Immunohistochemistry on synovial biopsies demonstrated an increased number of degranulated CD117⁺ mast cells in ACPA⁺ RA patients; IgE and FcεRI expression in synovial mast cells from ACPA⁺ RA patients was increased. In conclusion, our results show an immunological response of immune cells from ACPA⁺ RA patients in a citrulline-specific manner. Moreover, these data indicate a role for IgE-ACPAs and FcεRI-positive cells in the pathogenesis of RA.