T-cell abnormalities are present at high frequencies in patients with hypereosinophilic syndrome

Abstract

BackgroundA T-cell clone, thought to be the source of eosinophilopoietic cytokines, identified by clonal rearrangement of the T-cell receptor and by the presence of aberrant T-cell immunophenotype in peripheral blood defines lymphocytic variant of hypereosinophilic syndrome (L-HES). Design and MethodsPeripheral blood samples from 42 patients who satisfied the diagnostic criteria for HES were studied for T-cell receptor clonal rearrangement by polymerase chain reaction according to BIOMED-2. The T-cell immunophenotype population was assessed in peripheral blood by flow cytometry. The FIP1L1-PDGFRA fusion gene was detected by nested polymerase chain reaction. ResultsForty-two HES patients (18 males and 24 females) with a median age at diagnosis of 56 years (range 17-84) were examined in this study. Their median white blood cell count was 12.9×10 9 /L (range 5.3-121), with an absolute eosinophil count of 4.5×10 9 /L (range 1.5-99) and a median eosinophilic bone marrow infiltration of 30% (range 11-64). Among the 42 patients, clonal T-cell receptor rearrangements were detected in 18 patients (42.8%). Patients with T-cell receptor clonality included: T-cell receptor β in 15 patients (35%), Tcell receptor γ in 9 (21%) and T-cell receptor δ in 9 (21%) patients, respectively. Clonality was detected in all three T-cell receptor loci in 4 cases, in two loci in 7 patients and in one T-cell receptor locus in the remaining 7 patients. The FIP1L1-PDGFRA fusion transcript was absent in all but 2 patients with T-cell receptor clonality. Three patients out of 42 revealed an aberrant T-cell immunophenotype. In some patients, an abnormal CD4:CD8 ratio was demonstrated. ConclusionsT-cell abnormalities are present at high frequencies in patients with HES.

How I treat hypereosinophilic syndromes

“…30 Since that time, several large series of L-HES patients have been reported. 16,[31][32][33][34] Although listed as an exclusion criteria for a diagnosis of idiopathic HES, L-HES is not otherwise classified in the 2008 WHO guidelines. 5 Equally frequent in men and women, L-HES is characterized by a high prevalence of skin and soft tissue manifestations, elevated serum IgE, and thymus and activation regulated chemokine levels.…”

Case Report: Hypereosinophilic Syndrome Response to Infliximab in a Patient with Ulcerative Colitis

“…Serum tryptase, vitamin B12 and serum IgE have to be analyzed. A bone marrow aspiration and biopsy with immunohistochemical and molecular techniques (1,5) are necessary if all the previous studies are normal.…”

“…Treatment with alpha interferon, mepolizumab (anti-IL5), alemtuzumab (anti-CD52) and other chemotherapeutic agents such as cladribine, chlorambucil, vincristine, methotrexate, cyclosporine and etoposide have been evaluated in specific cases. Hematopoietic cell transplantation should be considered as the last therapeutic alternative when everything else has failed [1][2][3][4][5][6][7][8][9][10]. Anti-TNF administration has been reported to induce severe eosinophilic gastroenteritis in a patient with Crohn's Disease [11].…”

Imatinib mesylate for lymphocytic variant of hypereosinophilic syndrome

“…The theory of a secondary effect of eosinophils or chronic inflammation on clonal T-cell expansion does not easily apply to our patient because this clone was not diminished despite hematological remission and symptom relief. An incidental finding cannot be excluded but we believe that the specificity of the immunophenotype technique and the quantitative information provided may differentiate such cases from similar observations in the elderly or in autoimmune diseases that represent mainly CD4(1)CD8 (1) or oligoclonal CD81 T-cell expansions [3,4]. Nevertheless, clonality in CD3(2)CD4(1) cases should be demonstrated by TCR gene rearrangement studies due to the absence of surface T-cell receptor.…”