Valérie Gruart

Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation

The release of eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) was evaluated after incubation of eosinophils (EOSs) from allergic subjects with the specific allergen or with anti-IgE monoclonal antibodies (MAbs). High levels of EPO could be released after addition of the specific allergen (and not unrelated ones) or anti-IgE MAb. Moreover, EPO release with the two stimuli was significantly correlated both in allergic and in nonallergic patients. In the same supernatants, another granule protein, ECP, could not be detected, suggesting a lack of correlation between EPO and ECP release after IgE-dependent stimulation. However, when EOSs with surface-IgA antibodies were incubated with anti-IgA MAb, both EPO and ECP were released. In contrast, incubation of EOSs with anti-IgG MAb induced mainly the release of ECP and not EPO. These results indicate that pharmacologically active mediators can be released by EOSs from allergic and nonallergic patients on immunoglobulin-dependent activation. The results also confirm the hypothesis of a selective release of the various granule proteins and raise the question of transduction signals delivered by the three Fc receptors (Fc epsilon R, FC alpha R, and FC gamma R) present on human EOSs.

Presence of antibodies against endothelial cells in the sera of patients with episodic angioedema and hypereosinophilia.

We reported three additional cases of a newly described syndrome called episodic angioedema with hypereosinophilia. In order to investigate its pathophysiological mechanisms, four parameters were concurrently investigated, including blood eosinophil density, serum chemoattractant activity, serum major basic protein (MBP) levels and the presence of anti‐endothelial cell antibodies. Distribution of eosinophils through a metrizamide density gradient showed a preferential sedimentation of blood eosinophils in intermediate layers, clearly different from the hypodense cells (low‐density layers) identified in a group of seven patients with idiopathic hypereosinophilic syndrome (HES). In two of the three patients with cyclic angioedema. a chemotactic activity towards eosinophils was detected in the serum (30 ± 6 and 42 ± 12 eosinophils per high‐power field; P < 0.05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating anti‐endothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P < 0.01) or to patients with HES (P < 0.01). Specificity of the antibody for endothelial cells was demonstrated in the three patients studied by the absence of binding to various blood cells, including monocytes, lymphocytes, eosinophils and platelets. In one case (patient 2), the levels of anti‐endothelial cell antibodies, as well as the serum chemoattractant activity to eosinophils varied according to the successive acute phases of the disease. Although further investigations are needed to clarify the exact pathophysiology of this syndrome, and especially the possible participation of the anti‐endothelial cell antibodies in the cutaneous lesions, these data suggest that angioedema observed in this syndrome could result from the combined effects of activated eosinophils and of immunologically induced endothelial lesions.

Eosinophil IgE receptor and CD23

In the present review, eosinophil FcεRII was compared to CD23, a differentiation marker of B cells. Biochemical analysis revealed that molecules of similar molecular weight were immunoprecipitated from eosinophils and B cells by an anti-CD23 monoclonal antibody (mAb) or by BB10, an anti-eosinophil FcεRII. By flow cytometry, a correlation was found between the binding of anti-CD23 mAb and myeloma IgE. However, a low expression of different epitopes of CD23 was observed in various hypereosinophilic patients. Northern blot analysis of eosinophil RNA with the cDNA probe of CD23 revealed a weak message in only 3 of the 6 patients expressing membrane CD23. The inhibition by anti-CD23 mAbs of IgE-mediated cytotoxicity and IgE binding to eosinophils clearly indicated the participation of CD23 or a related moclecule in IgE-dependent eosinophil functions. However, the differential effects of anti-CD23 mAbs on eosinophils and B cells suggest major differences in the characteristics of the molecule expressed by eosinophils and by B cells.

The interleukin 2 receptor in the hypereosinophilic syndrome

The hypereosinophilic syndrome (HES) has been previously described as a clinicobiological entity characterized by a blood eosinophil count of over 1.5 x 10(9)/L of unknown cause associated with several clinical complications. In reality, HES is a heterogeneous group of diseases with variable and unpredictable progress in visceral lesions, thought to be related to the deleterious effects of tissue eosinophil infiltration. Various criteria for discrimination between benign and severe forms of HES have been described. These previous retrospective clinical investigations, using biological and clinical markers, have defined different stages of HES. It appears more relevant, however, to consider elements of disease activity by studying mechanisms of induction of persistent hypereosinophilia. The T-cell dependence of blood eosinophilia has led us to evaluate various markers of T-cell activation in particular. In the present review, we report previous results and perspectives suggested by the study of the interleukin 2 receptor in HES.