Eosinophilia Associated With CD3−CD4+ T Cells: Characterization and Outcome of a Single-Center Cohort of 26 Patients

Carpentier, Caroline; Verbanck, Sylvain; Schandené, Liliane; Heimann, Pierre; Trépant, Anne‐Laure; Cogan, Elie; Roufosse, Florence

doi:10.3389/fimmu.2020.01765

Cited by 31 publications

(54 citation statements)

References 42 publications

(75 reference statements)

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“…In their 2007 review of HES-related cardiovascular manifestations, Ogbogu et al mainly focused on cases of intracardiac thrombus and subsequent peripheral arterial emboli 3 . Overall, VT is poorly reported in the main series of patients with HES (whether clonal 23 , lymphocytic 24 or idiopathic 7 , 25 ) and EGPA is the sole eosinophil-related disease for which estimated rates of the prevalence of VT have been reported (ranging from 5 to 30% within series, and possibly higher in ANCA-negative patients) 26 , 27 . More recently, Maino et al reviewed published cases of thrombotic (including venous, arterial and mixed) events occurring in HES (n = 124), EGPA (n = 80) or parasitic infestations (n = 22), yet neither AEC at thrombosis nor long-term outcomes were reported 28 .…”

Section: Discussionmentioning

confidence: 98%

Venous thrombosis and predictors of relapse in eosinophil-related diseases

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Terrier

et al. 2021

Sci Rep

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Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6–7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10–62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94–29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

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Section: Discussionmentioning

confidence: 98%

Venous thrombosis and predictors of relapse in eosinophil-related diseases

Réau

Vallée

Terrier

et al. 2021

Sci Rep

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“…Although L-HES is an indolent lymphoproliferative disorder, the large majority of patients have normal circulating lymphocyte counts (10,11,13). We recently reported that the abnormal CD3 -CD4 + T cell subset represented less than 2% of total lymphocytes in 40% of patients (10), explaining that these cells rarely impact differential counts.…”

Section: Discussionmentioning

confidence: 99%

“…However, we recently reported that this T cell subset was very small (representing 2% or less of total lymphocytes) in a substantial proportion of patients, and was often over-looked during routine work-up (10). In this study, we show that when many events are acquired, the abnormal T cells appear as a tight cluster on CD3/CD4 dot plots, and they can be distinguished from monocytes based on their level of expression of CD4, similar to that of the normal CD3 + CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%

“…Timely diagnosis of L-HES is essential for optimal management, with implications both for follow-up and treatment. Indeed, patients with L-HES are at increased risk of developing T cell lymphoma generally several years after presentation (8), they often require higher OCS dosing regimens than patients with I-HES (9), and their response rates to classical second-line agents differ (10). The median delay before identification of CD3 -CD4 + cells after symptom onset was 3.5-4 years in the largest patient series published to date (10,11).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, patients with L-HES are at increased risk of developing T cell lymphoma generally several years after presentation (8), they often require higher OCS dosing regimens than patients with I-HES (9), and their response rates to classical second-line agents differ (10). The median delay before identification of CD3 -CD4 + cells after symptom onset was 3.5-4 years in the largest patient series published to date (10,11). This exposes patients to risks associated with high-dose OCS treatment, with persistent disease activity for prolonged periods whilst searching for effective OCS-sparing agents.…”

Section: Introductionmentioning

confidence: 99%

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

Carpentier

Schandené

Dewispelaere

et al. 2021

The Journal of Allergy and Clinical Immunology: In Practice

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BackgroundIdentification of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) is challenging, and has important prognostic and therapeutic implications. ObjectiveThis study was undertaken to assess diagnostic tools for L-HES and to develop evidence-based diagnostic recommendations. MethodsBiomarkers 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, TCR gene rearrangement patterns) were collected from medical files, while others were prospectively assessed on stored blood samples (serum CCL17/TARC levels, in-vitro cytokine production). ResultsThis 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 sensitive or specific for L-HES. In contrast, systematically enhanced expression of the T cell surface antigens CD2, CD45RO, and CD95 by these cells allowed for accurate detection by flow cytometry. Serum CCL17/TARC levels were significantly higher in L-HES compared to I-HES patients, 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. ConclusionAdapting the standard of procedure for T cell phenotyping in patients with unexplained Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationhypereosinophilia is currently the most reliable means of identifying those with CD3-CD4+ L-HES.

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World Health Organization‐defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management

2021

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Disease Overview: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary or clonal) disorders with potential for end-organ damage.Diagnosis: Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 Â 10 9 /L. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, next generation sequencing gene assays, and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.Risk Stratification: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2", and the myeloproliferative neoplasm subtype, "chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant HE is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion. Risk-adapted Therapy:The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (eg, < 1.5 Â 10 9 /L) without symptoms or signs of organ involvement, a watch and wait approach with close follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant HE and HES.Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, was recently approved by the US Food and Drug Administration for patients with idiopathic HES. The use of the IL-5 receptor antibody benralizumab, as well as other targeted therapies such as JAK2 and FGFR1 inhibitors, is under active investigation.

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Eosinophilia Associated With CD3−CD4+ T Cells: Characterization and Outcome of a Single-Center Cohort of 26 Patients

Abstract: (2020) Eosinophilia Associated With CD3 − CD4 + T Cells: Characterization and Outcome of a Single-Center Cohort of 26 Patients.

Cited by 31 publications

References 42 publications

Venous thrombosis and predictors of relapse in eosinophil-related diseases

Venous thrombosis and predictors of relapse in eosinophil-related diseases

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

World Health Organization‐defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management

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