CD3-CD4+ Lymphocytic Variant Hypereosinophilic Syndrome: Diagnostic Tools Revisited

Caroline Carpentier; Liliane Schandené; Laurent Dewispelaere; Pierre Heimann; Elie Cogan; Florence Roufosse

doi:10.1016/j.jaip.2021.01.030

CD3^-CD4⁺ Lymphocytic Variant Hypereosinophilic Syndrome: Diagnostic Tools Revisited

J Allergy Clin Immunol Pract. 2021 Jun;9(6):2426-2439.e7. doi: 10.1016/j.jaip.2021.01.030. Epub 2021 Feb 3.

Authors

Caroline Carpentier¹, Liliane Schandené², Laurent Dewispelaere³, Pierre Heimann³, Elie Cogan¹, Florence Roufosse⁴

Affiliations

¹ Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
² Laboratory of Immunology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
³ Department of Medical Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
⁴ Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium. Electronic address: froufoss@ulb.ac.be.

PMID: 33545400
DOI: 10.1016/j.jaip.2021.01.030

Abstract

Background: Identification of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) is challenging, and has important prognostic and therapeutic implications.

Objective: This study was undertaken to assess diagnostic tools for L-HES and to develop evidence-based diagnostic recommendations.

Methods: Biomarkers of T-cell-driven disease were compared between patients with L-HES versus idiopathic HES (I-HES) variants. Those performed routinely (serum immunoglobulin levels, T-cell phenotyping, T-cell receptor [TCR] gene rearrangement patterns) were collected from medical files, whereas others were prospectively assessed on stored blood samples (serum CCL17/thymus and activation regulated chemokine [TARC] levels, in vitro cytokine production).

Results: This study included 48 patients with I-HES and 20 with L-HES associated with a CD3^-CD4⁺ T-cell subset, including 7 with less than 5% aberrant cells. Neither increased serum immunoglobulin levels nor clonal TCR gene rearrangements were sufficiently sensitive or specific for L-HES. In contrast, systematically enhanced expression of the T-cell surface antigens CD2, CD5, CD45RO, and CD95 by these cells allowed for accurate detection by flow cytometry. Serum CCL17/TARC levels were significantly higher in patients with L-HES compared with those with I-HES, and a threshold of 3000 pg/mL allowed for detection of all subjects with L-HES with 75% specificity. Quantification of intracytoplasmic cytokine production by flow cytometry is the most reliable method for detection of enhanced type 2 cytokine expression, most notably for IL-4 and IL-13.

Conclusion: Adapting the standard of procedure for T-cell phenotyping in patients with unexplained hypereosinophilia is currently the most reliable means of identifying those with CD3^-CD4⁺ L-HES.

Keywords: CCL17/TARC; CD3(−)CD4(+) T cells; Hypereosinophilic syndrome; IL-5; Intracytoplasmic cytokines; Lymphocytic variant; T-cell phenotyping; TCR gene rearrangement.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD3 Complex
CD4-Positive T-Lymphocytes
Cytokines
Humans
Hypereosinophilic Syndrome* / diagnosis
Hypereosinophilic Syndrome* / genetics
T-Lymphocytes

Substances

CD3 Complex
Cytokines