Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity

Abstract

Eosinophils and their mediators play a crucial role in various reactive states such as bacterial and viral infections, chronic inflammatory disorders, and certain hematologic malignancies. Depending on the underlying pathology, molecular defect(s), and the cytokine- and mediator-cascades involved, peripheral blood and tissue hypereosinophilia (HE) may develop and may lead to organ dysfunction or even organ damage which usually leads to the diagnosis of a HE syndrome (HES). In some of these patients, the etiology and impact of HE remain unclear. These patients are diagnosed with idiopathic HE. In other patients, HES is diagnosed but the etiology remains unknown - these patients are classified as idiopathic HES. For patients with HES, early therapeutic application of agents reducing eosinophil counts is usually effective in avoiding irreversible organ damage. Therefore, it is important to systematically explore various diagnostic markers and to correctly identify the disease elicitors and etiology. Depending on the presence and type of underlying disease, HES are classified into primary (clonal) HES, reactive HES, and idiopathic HES. In most of these patients, effective therapies can be administered. The current article provides an overview of the pathogenesis of eosinophil-associated disorders, with special emphasis on the molecular, immunological, and clinical complexity of HE and HES. In addition, diagnostic criteria and the classification of eosinophil disorders are reviewed in light of new developments in the field.

Keywords: Classification; Eosinophilic leukemia; FIP1L1-PDGFRA; Hypereosinophilia; Hypereosinophilic Syndromes; Targeted therapy.

Fig. 1

The effects of various cytokines on migration of neoplastic eosinophils. The eosinophil cell line EOL-1 carrying FIP1L1-PDGFRA was loaded in the upper chambers of a Boyden-type double-chamber system. The lower chambers were supplemented with control medium or medium containing recombinant human SDF-1ɑ (25 ng/ml), IL-5 (100 ng/ml), eotaxin (500 ng/ml), FGF-1 (100 ng/ml), FGF-2 (100 ng/ml), PDGF-AA (100 ng/ml), or PDGF-BB (100 ng/ml). After 4 h (5% CO₂, 37 °C), the numbers of viable migrated cells collected in the lower chambers were measured by flow cytometry. Results are expressed as percent of all viable cells (100% input) and represent the mean ± S.D. of 3 independent experiments. Asterisk (*), p < 0.05 compared to medium control. Abbreviations: SDF-1, stroma cell–derived factor; IL-5, interleukin-5; FGF, fibroblast growth factor; PDGF, platelet-derived growth factor

Fig. 2

Expression of corona virus receptors on human eosinophils. EOL-1 cells (left panels) and normal peripheral blood (PB) eosinophils were stained with PE-conjugated antibodies against three corona virus receptors, namely CD13 (aminopeptidase-N: clone WM15), CD26 (DPPIV: clone M-A261), and CD147 (basigin: clone HIM-6). Antibody reactivity (orange histograms) was analyzed by flow cytometry. The isotype-matched control antibody is also shown (black open histograms). Abbreviations: CD, cluster of differentiation; PE, phycoerythrin; DPPIV, dipeptidyl-peptidase IV