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

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

doi:10.1016/j.jaip.2021.01.030

Cited by 14 publications

(14 citation statements)

References 33 publications

(25 reference statements)

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“…Hypereosinophilic syndrome In patients presenting with persistent unexplained HE, markedly elevated sTARC/CCL17 levels are associated with L-HES whereas normal values are observed in patients with no evidence for underlying Th2driven pathogenesis [136]. In a recent study on a large cohort of HES patients, our group determined that a threshold value of 3000 pg/ml should raise suspicion of L-HES [143] although similarly elevated levels were also observed in patients with I-HES presenting clinically as eosinophilic dermatitis. A rise in sTARC/CCL17 could also be an early marker heralding a disease flare in patients with episodic angioedema with eosinophilia associated with CD3 -CD4 + T cells [95].…”

Section: Discussionmentioning

confidence: 82%

What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?

Catherine,

Roufosse

2021

Semin Immunopathol

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Eosinophilic disorders encompass a large spectrum of heterogeneous diseases sharing the presence of elevated numbers of eosinophils in blood and/or tissues. Among these disorders, the role of eosinophils can vary widely, ranging from a modest participation in the disease process to the predominant perpetrator of tissue damage. In many cases, eosinophilic expansion is polyclonal, driven by enhanced production of interleukin-5, mainly by type 2 helper cells (Th2 cells) with a possible contribution of type 2 innate lymphoid cells (ILC2s). Among the key steps implicated in the establishment of type 2 immune responses, leukocyte recruitment toward inflamed tissues is particularly relevant. Herein, the contribution of the chemo-attractant molecule thymus and activation-regulated chemokine (TARC/CCL17) to type 2 immunity will be reviewed. The clinical relevance of this chemokine and its target, C-C chemokine receptor 4 (CCR4), will be illustrated in the setting of various eosinophilic disorders. Special emphasis will be put on the potential diagnostic, prognostic, and therapeutic implications related to activation of the TARC/CCL17-CCR4 axis. Keywords Thymus and activation-regulated chemokine (TARC) . CCL17 . C-C chemokine receptor 4 (CCR4) . Eosinophils . Eosinophilic disorders . Hypereosinophilic syndromes Abbreviations AA Allergic asthma ABPA Allergic bronchopulmonary aspergillosis ADCC Antibody-dependent cell cytotoxicity AEC Absolute eosinophil count AEP Acute eosinophilic pneumonia AITL Angioimmunoblastic T cell lymphoma ALI Acute lung injury ANCA Anti-neutrophil cytoplasmic antibody ARDS Acute respiratory distress syndrome ATLL Adult T cell leukemia/lymphoma AUC Area under the curve BALF Bronchoalveolar lavage fluid This article is a contribution to the Special issue on: Eosinophils -Guest

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Section: Discussionmentioning

confidence: 82%

What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?

Catherine,

Roufosse

2021

Semin Immunopathol

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“…Furthermore, the definitions of L-HES have varied over time as the World Health Organization (WHO) classifications of haematological malignancies and eosinophilia have changed, and patients with L-HES included in earlier studies may not align with those included in more recent studies. 2,7 Studies variably defined patients as having L-HES based on flow cytometry, PCR analysis of the TCR, or both. Future studies should use rigorous definitions for L-HES, with the degree of certainty in the diagnosis and inclusion of diagnostic considerations in difficult cases.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, there are no universally accepted criteria for diagnosis of L‐HES and small reactive populations of aberrant T cells may be seen in other conditions, so patients should be carefully evaluated for mimickers of L‐HES, e.g. eosinophilic granulomatosis with polyangiitis (EGPA), immunoglobulin G4‐related disease (IgG4‐RD) and autoimmune disease 5–7 …”

Section: Figurementioning

confidence: 99%

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Treatment of lymphocyte‐variant hypereosinophilic syndrome (L‐HES): what to consider after confirming the elusive diagnosis

2021

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Lymphocyte-variant hypereosinophilic syndrome (L-HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin-5 (IL-5). Treatment is challenging because L-HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L-HES. In all, 25 studies were selected; two were randomised controlled trials of IL-5 blockade, which included some patients with L-HES, and the rest were observational studies. Corticosteroids are often used as first-line therapy, but patients with L-HES have lower response rates than other types of HES. Treatments that reduce symptoms and steroid dependence in some patients include interferonalpha (IFN-a), anti-IL-5 monoclonal antibodies, cyclosporine and mycophenolate. These drugs target T-cell activation and proliferation, or IL-5 directly. Although effective, IFN-a and cyclosporine were commonly reported to cause side-effects resulting in discontinuation. Alemtuzumab can induce remissions, but these are generally short lived. The anti-IL-5 monoclonal antibodies mepolizumab and benralizumab are effective and well tolerated, but with a high rate of relapse once withdrawn. Hydroxyurea, methotrexate, imatinib were unsuccessful in most patients studied. More prospective clinical trials are needed for patients with L-HES.

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“…CD3 - CD4 + is a heterogeneous group. CD4 has been reported to express in T cells (CD3 − CD4 + T cells) [ 39 ], B cells [ 40 ], NKs [ 41 ], DCs [ 42 ], macrophages [ 43 ], monocytes [ 44 ], eosinophils [ 45 ], etc. Among these cells, CD4+ NKs, DCs, macrophages and monocytes have been reported to express TNF-α [ 41 , 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Downregulated TNF-α Levels after Cryo-Thermal Therapy Drive Tregs Fragility to Promote Long-Term Antitumor Immunity

Lou

Wang

Peng

et al. 2021

IJMS

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Immunotherapy has emerged as a therapeutic pillar in tumor treatment, but only a minority of patients get benefit. Overcoming the limitations of immunosuppressive environment is effective for immunotherapy. Moreover, host T cell activation and longevity within tumor are required for the long-term efficacy. In our previous study, a novel cryo-thermal therapy was developed to improve long-term survival in B16F10 melanoma and s.q. 4T1 breast cancer mouse models. We determined that cryo-thermal therapy induced Th1-dominant CD4+ T cell differentiation and the downregulation of Tregs in B16F10 model, contributing to tumor-specific and long-lasting immune protection. However, whether cryo-thermal therapy can affect the differentiation and function of T cells in a s.q. 4T1 model remains unknown. In this study, we also found that cryo-thermal therapy induced Th1-dominant differentiation of CD4+ T cells and the downregulation of effector Tregs. In particular, cryo-thermal therapy drove the fragility of Tregs and impaired their function. Furthermore, we discovered the downregulated level of serum tumor necrosis factor-α at the late stage after cryo-thermal therapy which played an important role in driving Treg fragility. Our findings revealed that cryo-thermal therapy could reprogram the suppressive environment and induce strong and durable antitumor immunity, which facilitate the development of combination strategies in immunotherapy.

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

Cited by 14 publications

References 33 publications

What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?

What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?

Treatment of lymphocyte‐variant hypereosinophilic syndrome (L‐HES): what to consider after confirming the elusive diagnosis

Downregulated TNF-α Levels after Cryo-Thermal Therapy Drive Tregs Fragility to Promote Long-Term Antitumor Immunity

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