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Review
. 2021 Jun;43(3):423-438.
doi: 10.1007/s00281-021-00863-y. Epub 2021 May 30.

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

Peter Valent  1   2 , Lina Degenfeld-Schonburg  3 , Irina Sadovnik  3   4 , Hans-Peter Horny  5 , Michel Arock  6 , Hans-Uwe Simon  7   8   9 , Andreas Reiter  10 , Bruce S Bochner  11
Affiliations
Review

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

Peter Valent et al. Semin Immunopathol. 2021 Jun.

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.

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Conflict of interest statement

The authors declare that they have no study-related specific conflicts of interest. The authors declare the following conflicts of interest outside of this project: P.V. received a research grant from Pfizer, Celgene, and Novartis, and consultancy-related honoraria from Novartis, Pfizer, Celgene, Blueprint, Incyte, Abbvie, AB Science, Accord, Alexion, Orphan Pharmaceuticals, and TLL The Longevity Labs. H.U.S. is a consultant for GlaxoSmithKline. A.R. received consultancy honoraria from Novartis, Incyte, GSK, Astra Zeneca, Blueprint, Celgene/BMS, and Abbvie. B.S.B. receives publication-related royalty payments from Elsevier and UpToDate. He receives remuneration for consulting services (Blueprint Medicine, Glaxo SmithKline, Sanofi/Regeneron) and for serving on the scientific advisory board of Third Harmonic Bio. He also receives remuneration for serving on the scientific advisory board of Allakos, which he co-founded, and owns stock in Allakos. He is a co-inventor on existing Siglec-8-related patents and thus may be entitled to a share of royalties received by Johns Hopkins University during development and potential sales of such products. The terms of this arrangement are being managed by Johns Hopkins University and Northwestern University in accordance with their conflict of interest policies.

Figures

Fig. 1
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
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
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