Although inhibitory Fcγ receptors have been demonstrated to promote mucosal tolerance, the role of activating Fcγ receptors in modulating T helper type (Th)2-dependent inflammatory responses characteristic of asthma and allergies remains unclear. Here, we demonstrate that signaling via activating Fcγ receptors in conjunction with Toll-like receptor 4 stimulation modulated cytokine production from bone marrow–derived dendritic cells (DCs) and augmented their ability to promote Th2 responses. Ligation of the low affinity receptor FcγRIII was specifically required for the enhanced Th2 responses, as FcγRIII−/− DCs failed to augment Th2-mediated airway inflammation in vivo or induce Th2 differentiation in vitro. Further, FcγRIII−/− mice had impaired Th2 cytokine production and exhibited reduced airway inflammation, whereas no defect was found in FcγRI−/− mice. The augmentation of Th2 immunity was regulated by interleukin 10 production from the DCs but was distinct and independent of the well-established role of FcγRIII in augmenting antigen presentation. Thus, our studies reveal a novel and specific role for FcγRIII signaling in the regulation of Th cell responses and suggest that in addition to immunoglobulin (Ig)E, antigen-specific IgG also contributes to the pathogenesis of Th2-mediated diseases such as asthma and allergies.

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Signaling through FcγRIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation

Fifty-one patients were referred in one year (1992) for investigation of immediate type anaphylactic/anaphylactoid reactions during anaesthesia. Skin prick tests were made with 23 anaesthetic and associated agents in the concentrations used clinically. Definite or probable causes were identified by immediate type wealing reactions, supported by the clinical history in 36 of the 46 in whom a diagnosis of anaphylaxis was made. These comprised mainly the neuromuscular relaxants, chiefly suxamethonium (18); atracurium (6); gallamine (2); one each alcuronium; pancuronium; vecuronium and tubocurarine, as well as alfentanil (1); Gelofusine (2); cefuroxime (1) and latex (2). The materials for performing the skin prick test are readily available and it can be very helpful in making important aetiological diagnoses.

Anaphylactic/anaphylactoid reactions to anaesthetic and associated agents. Skin prick tests in aetiological diagnosis.

BRONCHIAL PROVOCATION TESTS IN ATOPIC PATIENTS WITH ALLERGEN-SPECIFIC IgG4 ANTIBODIES

Most anaphylactic disorders, allergic rhinitis, asthma, allergic urticaria and angio-oedema, and anaphylactic gastro-enteritis, are mediated by IgE reaginic antibodies. An antibody mediating anaphylactic sensitivity binds to specific receptors on mast cell and basophil membranes by the Fc portion of the molecule, leaving the Fab portion free to react with antigen. IgE is the classic example of an anaphylactic antibody i its properties are well known.

The clinical relevance of heat-stable, short-term sensitizing anaphylactic IgG antibodies (IgG S-TS) and of related activities of IgG4 and IgG2.

The antigen non-specific release of histamine by synthetic neuromuscular blocking agents is well known, though our review of thirty-two cases reported in the literature of anaphylactoid reactions to succinylcholine, shows that there is insufficient evidence to determine whether the signs are due to anaphylactic or to anaphylactoid reactions. We have examined thirteen cases in whom evidence of anaphylactic sensitization was examined by direct skin tests (in eleven cases) Prausnitz--Kustner tests (in five), rabbit basophil degranulation, Shelley test (in twelve) and human basophil degranulation (in seven). These tests were done on two to four occasions, and the optimal period for the first test ascertained to be 6 to 12 weeks after the episode. All eleven patients examined by direct skin tests showed evidence of anaphylactic sensitivity, and in three of five cases the sensitivity could be transferred by the Prausnitz--Kustner procedure. In one of these P--K tests there was evidence of both IgE and of IgG S-TS antibodies (heat-stable antibody conferring sensitivity for 2 hr). Particular susceptibilities to adverse reactions of this drug appear to be prior drug allergy (in 50% of cases), several previous anaesthetics, and atopy.

Anaphylaxis due to succinylcholine. Immunoallergological study of thirteen cases.

The sera of atopic and non-atopic persons with allergic pulmonary disorders were examined for long-term sensitizing, IgE and short-term sensitizing heat-stable (S-TS) antibodies which were present separately or together in the sera of some patients sensitive to antigens such as budgerigar serum proteins and Aspergillus funigatus. In fourteen atopic patients with extrinsic asthma, six had both types of antibody to common allergens, and of nine non-atopic patients with crytogenic (intrinsic) asthma, four had only heat-stable short-term sensitizing antibodies. The sera of atopic subjects with type I prick test reactions and positive RAST's, showed specific IgE antibody by baboon PCA tests to budgerigar serum proteins, A. funigatus, Timothy grass pollen extract and hen egg extract, and not to Dermatophagoides farinae, possibly because of naturally occurring mite antibodies in the baboon. The sera of non-atopic asthmatics, who had given negative prick test but positive immediate, dual or late intracutaneous tests, and only late asthmatic reactions, contained precipitins in most cases and gave little or no RAST reaction. On baboon PCA these sera contained either, S-TS antibody alone, or S-TS plus long-term sensitizing antibody, or long-term sensitizing antibody alone. Some of the sera with long-term sensitizing antibody contained blocking antibody which could diffuse away in the 24 hr delay for the baboon PCA test and could also be responsible for the negative RAST. Tests with insoluble anti-IgE immuno-adsorbents on two sera from persons sensitive to aspergillus confirmed that the S-TS activity was not due to IgE, and on two sera with negative RAST and negative prick tests to budgerigar serum antigens confirmed that the 24 hr monkey PCA responses were due to IgE.

Clinical correlations between long-term (IgE) and short-term (IgG S-TS) anaphylactic antibodies in atopic and 'non-atopic' subjects with respiratory allergic disease.

B. Stenius-Aarniala

Papers

Clinical correlations between long-term (IgE) and short-term (IgG S-TS) anaphylactic antibodies in atopic and 'non-atopic' subjects with respiratory allergic disease.