PMID- 33545400 OWN - NLM STAT- MEDLINE DCOM- 20210708 LR - 20210708 IS - 2213-2201 (Electronic) VI - 9 IP - 6 DP - 2021 Jun TI - CD3(-)CD4(+) Lymphocytic Variant Hypereosinophilic Syndrome: Diagnostic Tools Revisited. PG - 2426-2439.e7 LID - S2213-2198(21)00158-6 [pii] LID - 10.1016/j.jaip.2021.01.030 [doi] AB - 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. CI - Copyright (c) 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. FAU - Carpentier, Caroline AU - Carpentier C AD - Department of Internal Medicine, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Schandene, Liliane AU - Schandene L AD - Laboratory of Immunology, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Dewispelaere, Laurent AU - Dewispelaere L AD - Department of Medical Genetics, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Heimann, Pierre AU - Heimann P AD - Department of Medical Genetics, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Cogan, Elie AU - Cogan E AD - Department of Internal Medicine, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Roufosse, Florence AU - Roufosse F AD - Department of Internal Medicine, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium; Institute for Medical Immunology, Universite Libre de Bruxelles, Gosselies, Belgium. Electronic address: froufoss@ulb.ac.be. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210203 PL - United States TA - J Allergy Clin Immunol Pract JT - The journal of allergy and clinical immunology. In practice JID - 101597220 RN - 0 (CD3 Complex) RN - 0 (Cytokines) SB - IM MH - CD3 Complex MH - CD4-Positive T-Lymphocytes MH - Cytokines MH - Humans MH - *Hypereosinophilic Syndrome/diagnosis/genetics MH - T-Lymphocytes OTO - NOTNLM OT - CCL17/TARC OT - CD3(-)CD4(+) T cells OT - Hypereosinophilic syndrome OT - IL-5 OT - Intracytoplasmic cytokines OT - Lymphocytic variant OT - T-cell phenotyping OT - TCR gene rearrangement EDAT- 2021/02/06 06:00 MHDA- 2021/07/09 06:00 CRDT- 2021/02/05 20:11 PHST- 2020/10/07 00:00 [received] PHST- 2021/01/13 00:00 [revised] PHST- 2021/01/16 00:00 [accepted] PHST- 2021/02/06 06:00 [pubmed] PHST- 2021/07/09 06:00 [medline] PHST- 2021/02/05 20:11 [entrez] AID - S2213-2198(21)00158-6 [pii] AID - 10.1016/j.jaip.2021.01.030 [doi] PST - ppublish SO - J Allergy Clin Immunol Pract. 2021 Jun;9(6):2426-2439.e7. doi: 10.1016/j.jaip.2021.01.030. Epub 2021 Feb 3.