[A decrease in the basophilic granulocyte count of the blood during exacerbation of the idiopathic nephrotic syndrome].
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A case of anaphylactic reaction to an infusion of modified fluid gelatin (Plasmagel) which occurred just before the induction of anaesthesia is reported. The allergic origin of this side effect was sought by a human basophil degranulation test (Benveniste test) which proved to be positive. Intolerance reactions to gelatins have up to now been little described in the French literature (in contrast to the German literature). Their mechanism remains poorly understood, even though there are many arguments in favour of a sensitivation phenomenon which would confirm the antigenic role, denied by some, of modified fluid gelatins employed in human clinical use (with the possibility of crossover allergy). The diagnosis and treatment of such complications are reviewed in the light of their mechanism.
The first case of haemolytic anaemia with thrombocytopenia and acute renal failure induced by ingestion of aspirin in a 22-year old woman is reported. An IgM anti-aspirin antibody which agglutinated erythrocytes of the patient and of ABO compatible donors in the presence of aspirin was isolated in the serum. In addition, the allergic nature of the patient's hypersensitivity to aspirin was confirmed by positive lymphocyte transformation and basophil degranulation tests in the presence of the drug.
Renal involvement is not frequently observed during therapy with clometacine and its mechanism not fully understood. We report on a case of acute renal failure occurring four times in conjunction with acute hepatitis before the causative effect of clometacine was demonstrated. Drug hypersensitivity was documented by anatomical findings consisting in renal interstitial infiltration by mononuclear cells and eosinophils and by hypereosinophilia, increase in plasma IgE and a positive basophil degranulation test.
On the basis of the CD 63 bi-modal expression on the membrane of activated basophils, we set up a flow cytometric method for the analysis of human basophils activation by an anti-IgE and anti-CD 63 double labelling. We demonstrated that the statistical characteristics of the percentages of activation obtained by an anti-IgE stimulation allowed the use of this method for pharmacological studies. The percentages of activation were of the same order of magnitude than those obtained by histamine release. CD 63 expression was also observed for a low affinity allergen such as the sulfonyl-HSA conjugate used for sulfites hypersensibility diagnosis, healthy donors being negative. This method, which can be automatized may represent an interesting candidate in the field of hapten hypersensitivity which lacks of reliable diagnostical methods.
We examined subcellular histamine localizations in purified human basophils that were stimulated to degranulate with FMLP using an ultrastructural enzyme-affinity technique. Basophils were collected at early (0, 20 seconds, 1 minute) and late (10 minutes to 6 hours) time points poststimulation and were prepared for routine ultrastructural and diamine oxidase-gold (DAO-gold) cytochemical analysis. Histamine was present in unaltered cytoplasmic secretory granules (30.77 gold particles per square micrometer; P < .001 compared with background); specificity controls (histamine absorption, diamine oxidase digestion) abrogated granule labeling for histamine. Altered granules in stimulated cells were not significantly labeled for histamine, as compared with background (P = not significant); unaltered granules in the same cells contained more histamine than altered granules (P < .05). During recovery times, spanning 10 minutes to 6 hours, granules again appeared to be electron-dense and contained histamine (33.49/microns2; P = not significant as compared with unaltered granules in 1-minute FMLP-stimulated cells, and P < .05 as compared with altered granules in 1-minute FMLP-stimulated samples). Other structures devoid of histamine in actively secreting cells included extruded granules and intragranular and extruded Charcot-Leyden crystals. Recovering basophils displayed morphologic evidence of material and membrane conservation, granule content condensation, and biosynthesis. Subcellular histamine-rich sites in actively recovering basophils included condensing granules and collections of cytoplasmic vesicles in three locations: beneath the plasma membrane, adjacent to granules, and in the Golgi region. These studies show that unaltered granules of actively releasing human basophils, as well as similar granules that are reconstituted after FMLP-stimulated degranulation, contain histamine, but that altered granules in stimulated cells undergoing degranulation are devoid of histamine. Reconstitution of histamine-rich granules is associated with DAO-gold-positive cytoplasmic vesicles, suggesting transport of histamine derived from either new synthesis, re-uptake of released histamine, or both, to reconstituted granules.
Molecular characterization of allergens by recombinant DNA technology has made rapid progress in the recent few years. In the present study we immunized mice with aluminum hydroxide-adsorbed purified recombinant major timothy grass pollen allergens (rPhl p 1, rPhl p 2, rPhl p 5), dog albumin, a major animal dander allergen, and proteins with low (beta-lactoglobulin) or no (ribulose diphosphate carboxylase) allergenic potential in humans. Allergens that bind high levels of IgE in humans (Phl p 1, Phl p 5, dog albumin) induced high IgE and IgG1 levels in mice, whereas proteins with little or no allergenic activity in humans failed to induce significant IgE and IgG1 levels in mice. Continuous immunization for a period of 27 wk resulted in the production of mouse IgG1 Abs that recognized recombinant allergen fragments/epitopes defined by IgE Abs of allergic patients. As a consequence, allergen-specific mouse Abs strongly inhibited human IgE binding to the allergens and suppressed the allergen-induced histamine release from human basophils. In summary, our data indicate that 1) the allergenic potency of a protein may be related to its overall immunogenicity and 2) prolonged immunization with single purified recombinant allergens induces protective IgG Abs. The presented experimental in vivo/in vitro system allows the evaluation of Ag preparations (e.g., recombinant allergens) to be used for immunotherapy in humans.
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The Spanish Societies of Allergology and Anesthesiology have established a protocol for action for the performance of allergy tests for anesthesia. The protocol was published by the General Directorate of INSALUD, along with an informed consent form for general and loco-regional anesthesia, on 30 June 1994. Despite this, demands for care and requests for allergologic and anesthetic studies have increased. This review examines the diagnostic, preventive, and therapeutic criteria for adverse reactions during general anesthesia according to the most relevant international literature. Pseudoallergic reactions are one of the most frequent and important adverse reactions that occur during general anesthesia. These reactions are caused by the release of histamine and, probably, other mediators. The histamine-releasing effect depends on the dose of the medication. The most potent medications are morphine and almost all muscular relaxants, in the following proportions (succinylcholine: 43%; vecuronium: 37%; pancuronium: 13%; alcuronium: 76%; atracurion: 6.8%; galamine: 56%). Somewhat less than 50% of all severe intraoperative allergic reactions are really anaphylactoid reactions. The mediators involved in anaphylactic/anaphylactoid responses are: IgE in type I hypersensitivity mechanisms, IgA, immunocomplexes, complement activated by an alternative pathway, tryptase, and histamine. Numerous and varied agents are involved. Table III lists general intravenous anesthetics; table IV shows muscular relaxants. According to national studies, intraoperative latex sensitization occurs in 1% to 5% of health-care personnel and 40% of children with spina bifida. More than 6% of blood donors have IgE against latex. Cross-reactions between latex and fruit proteins, such as banana and kiwi, have been reported. As many as 50% of patients with latex allergy have such cross-reactions, according to some authors. Diagnostic methods include skin tests, challenge, histamine release test, RIA, human basophil optical degranulation test, and ImmunoCAP. Skin tests are the technique most often used in Allergology Units in Spain. Risk factors are debated. Although the female sex is accepted as predominant, atopy is controversial. The only known negative factor is the insertion of an endotracheal tube in asthmatic patients. Prevention should begin with the selection of less potent drugs, such as histamine releasing agents. Slow administration of drugs, as opposed to bolus administration, has been demonstrated to be more effective. The use of combined H1 and H2 antihistamines as a preanesthetic medication can significantly reduce tachycardia/bradycardia, hypotension, skin response, and even gastric pH changes induced by histamine release.
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Clinical symptoms of immediate-type hypersensitivity (ITH) and specific IgE against Echinococcus granulosus antigens are frequently present in patients with hydatid cysts. In alveolar echinococcosis (AE) due to E. multilocularis, clinical manifestations related to ITH have never been reported. The IgE-dependent humoral immune response was evaluated in 30 patients with AE. Circulating specific IgE (sIgE) were determined with two different methods of radio-allergo-sorbent test. Serum sIgE were determined sequentially in 18 patients over 15 months. Specific IgE bound to circulating basophils were assessed with two tests in vitro, measuring specific degranulation and histamine release. The respective abilities of E. granulosus and E. multilocularis antigens to reveal bound and circulating IgE antibodies were also assayed. Despite the absence of clinical symptoms of ITH and the frequent lack of circulating sIgE, an immunological response involving IgE was always present in human AE: basophil-bound sIgE were revealed in every patient by histamine release and degranulation tests; these tests were constantly negative in control subjects. Echinococcus granulosus extracts were more effective for detecting circulating sIgE; however E. multilocularis antigenic preparation induced a histamine release significantly higher than E. granulosus extracts. These results suggest that IgE-dependent humoral immune response could play a role in the host-parasite relationship in AE. Moreover, the sensitivity of the tests used to detect basophil-bound sIgE was higher than that of the usual serological tests, and the basophil degranulation test could be used to confirm diagnosis of AE in endemic countries.
The author has designed a human basophil degranulation test based on a one-step method of basophil staining after exposure to a specific allergen. This very simple test is now commercially available as a ready-to-use kit. It explores allergic sensitivity at cellular level, probably through IgE-dependent sensitization of the basophil. It correlates positively with histamine release and the radio-allergo-sorbent test (RAST) and detects sensitivity to common allergens as well as to foods and chemicals, including drugs. In its present form, the test provides a simple, inexpensive and reliable means of diagnosing allergic diseases in vitro but does not lend itself to mass investigations. It has recently been developed further and can now be performed on the automatic Hemalog D Technicon machine.
A human basophil degranulation (HBD) performed on an enriched basophil suspension (by gradient density) was applied in 95 subjects with 3 dilutions of grass pollen extract. Concordance with intradermal skin-test (ST) results reached 90% for wheal and 94% for flare. In 45 positive ST subjects, mean (+/- s.e.m.) of degranulation index was 54,1 +/- 4,2, 54,9 +/- 4,7 and 35,7 +/- 4,9 respectively for dilutions of 10(-4), 10(-6) and 10(-8) of grass pollen. Mean was 6,1 +/- 1,6, 8,2 +/- 1,7 and 8,5 +/- 1,6 in 50 negative ST subjects. In positive ST patients, a significant correlation (r = 0,53 p less than 0,001) appeared between ST diameter (flare) and degranulation index. HBD appears as reliable as RAST or automated histamine analysis but more easy to perform. It permits pharmacological studies of drugs inhibiting human basophil degranulation.
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Diclofenac (Dc) induces an IgE-independent basophil (Ba) degranulation in susceptible individuals. CD63 Ba expression is utilized as an in vitro test for diagnosis of drug hypersensitivity. We tested the ability of Dc to induce CD63 Ba expression by flow cytometry (BAT) and Ba degranulation using light microscopy (HBDT) in patients sensitive to Dc. We studied 14 patients with diclofenac hypersensitivity, also two patients sensitive to Dermatophagoides pteronyssinus (Dp), and 12 normal controls. HBDT was performed by mononuclear cells toluidine blue staining. BAT determined CD63 expression in antiCD63/anti-IgE/anti-CD45-labelled whole blood. In each case, the percentage of activated Ba post-stimulation with 1 and 10 microg/ml Dc was determined. Positive controls included N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide-induced activation. IgE-mediated Ba activation was induced with a Dp allergenic extract. With Dc 1 microg/ml, mean HBDT in Dc-susceptible individuals was 33.62 +/- 18.35% and 8.49 +/- 4.79% in controls (P = 0.0001). Mean BAT was 2.04 +/- 1.68% and 1.93 +/- 1.40% in controls (P = 0.8). Ba preincubation with Dc did not affect fMLP-induced CD63 expression, neither in Dc-sensitive individuals (P = 0.8) (n = 4) nor in subjects without Dc hypersensitivity (P = 0.25) (n = 4). Ba from the two patients sensitive both to Dc and Dp responded to Dp but not to Dc by BAT: Dc, 1.99 +/- 0.78%; Dp: 60.87 +/- 9.28%; but showed degranulation by HBDT: Dc, 30.53 +/- 1.02%, Dp: 48.78 +/- 22.17%. Dc induces Ba degranulation in sensitive patients in a way that does not induce CD63 expression and is different from IgE-mediated and fMLP-mediated degranulation. Our results suggest that CD63 expression is not a reliable diagnostic method for diclofenac allergy.