Histamine release positive test associates with disease remission in chronic spontaneous urticaria: a proof-of-concept study.

SUMMARY: Background. Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU). Objectives and methods. Twenty CSU patients unresponsive to antihistamine treatment were enrolled in order to evaluate the correlations between HR test results and demographic features, quality of life, disease activity, clinical course, and autologous serum and plasma skin tests (ASST and APST). Results. All patients with positive HR test (9/9, 100%) had a more severe disease activity at onset (urticaria activity score, UAS > 2) when compared to negative HR test patients (5/11; p = 0.04). Quality of life questionnaire's results were not substantially different between HR positive and negative subgroups at baseline (p > 0.05), and results of HR test and ASST/APST did not co-segregate (p > 0.05). After 12 months, patients with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0.027). Conclusions. Positive HR test may predict spontaneous CSU remission at 12 months.

Basophil Histamine Release Induced by Amoxicilloyl-poly-L-lysine Compared With Amoxicillin in Patients With IgE-Mediated Allergic Reactions to Amoxicillin.

BACKGROUND: Amoxicillin (AX) is the ß-lactam most often involved in IgE-mediated reactions. Diagnosis is based mainly on skin testing, although sensitivity is not optimal. We produced a new AX derivative, amoxicilloyl-poly-L-lysine (APL), and analyzed its recognition of IgE using the passive histamine release test (pHRT). METHODS: The study population comprised patients (n=19) with confirmed AX allergy and specific IgE to AX and controls (n=10) with good tolerance to AX. pHRT was performed using "IgE-stripped" blood from a single donor that was sensitized in vitro by patient sera and incubated with AX or APL. Histamine release was determined and expressed as nanograms of histamine released per milliliter of blood. RESULTS: The clinical symptoms were anaphylaxis (n=9), urticaria (n=7), erythema (n=2), and nondefined immediate reactions (n=1). The median (IQR) time interval between reaction and study was 90 (60-240) days and between drug intake and development of symptoms 24 (10-60) minutes. The median sIgE level was 3.37 (0.95-5.89) kUA/L. The sensitivity of pHRT to APL was 79% and the specificity 100%, which were higher than data obtained with pHRT to AX (63% sensitivity and 90% specificity). There was a positive correlation between maximal histamine release levels obtained with AX and APL (r=0.63). CONCLUSIONS: In patients with immediate hypersensitivity reactions to AX, APL showed higher sensitivity and specificity than the culprit drug, AX, when tested in vitro by pHRT. This indicates that APL can improve the in vitro diagnostic accuracy of allergic reactions to AX. Further assessment of skin testing is necessary.

Basophil histamine release induced by amoxicilloyl-poly-L-lysine compared with amoxicillin in patients with IgE-mediated allergic reactions to amoxicillin

No disponible

IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes.

BACKGROUND: IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have been shown to express complementary and partially overlapping roles, it is not clear whether a similar IgE/TNF-α/MMP-9 axis exists in the human basophil. The purpose of this study was thus to investigate whether IgE-mediated activation of human basophils induces TNF-α and MMP-9 release. METHODS: Human peripheral blood mononuclear cells (PBMC), isolated basophils and monocytes were stimulated up to 21 h with anti-IgE. Mediator releases were assessed by ELISA, and surface expressions of mediators were detected by flow cytometry. Upregulation of cytokine production was detected by Western blot and polymerase chain reaction (PCR). RESULTS: IgE-mediated activation of basophils induced the synthesis and release of both TNF-α and MMP-9 from PBMC. In contrast, IgE-mediated activation of purified basophils induced the release and cellular expression of TNF-α but not MMP-9. Isolated monocytes did not release MMP-9 upon anti-IgE stimulation, but MMP-9 release was induced by stimulating monocytes with supernatants from activated basophils, and this release was inhibited by anti-TNF-α neutralizing antibodies. CONCLUSION: Our results strongly indicate that human basophils release TNF-α following IgE-dependent activation and that this cytokine subsequently stimulates MMP-9 release from monocytes. These findings support a direct involvement of basophils in inflammation as well as suggesting a role for the basophil in tissue remodelling.