Hypereosinophilic syndromes

Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia (> 1.5 × 109/L for more than six consecutive months) associated with evidence of eosinophil-induced organ damage, where other causes of hypereosinophilia such as allergic, parasitic, and malignant disorders have been excluded. Prevalence is unknown. HES occur most frequently in young to middle-aged patients, but may concern any age group. Male predominance (4–9:1 ratio) has been reported in historic series but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a recently characterized disease variant. Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases. Other frequently observed complications include hepato- and/or splenomegaly, eosinophilic gastroenteritis, and coagulation disorders. Recent advances in underlying pathogenesis have established that hypereosinophilia may be due either to primitive involvement of myeloid cells, essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the FIP1L1-PDGFRA fusion gene (F/P+ variant), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant), most frequently characterized by a CD3-CD4+ phenotype. Diagnosis of HES relies on observation of persistent and marked hypereosinophilia responsible for target-organ damage, and exclusion of underlying causes of hypereosinophilia, including allergic and parasitic disorders, solid and hematological malignancies, Churg-Strauss disease, and HTLV infection. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic and functional approaches. Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P+ patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody, is an effective corticosteroid-sparing agent for F/P-negative patients. Prognosis has improved significantly since definition of HES, and currently depends on development of irreversible heart failure, as well as eventual malignant transformation of myeloid or lymphoid cells

High serum thymus and activation-regulated chemokine levels in the lymphocytic variant of the hypereosinophilic syndrome

The idiopathic hypereosinophilic syndrome is associated with expansion of an IL-5-producing T-cell subset in a subgroup of patients. Identification of such patients is critical to adequate management because there is some evidence that they present an increased risk for development of T-cell lymphoma. Although the T(H)2-like cells often bear an aberrant surface phenotype and can readily be detected with flow cytometry, we now show that lymphocyte phenotyping might be normal in some cases. In contrast, serum thymus and activation-regulated chemokine levels are consistently increased in such patients compared with others with persistent idiopathic hyper-eosinophilia and could therefore represent a useful diagnostic tool.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Intramyocardial transplantation of mesenchymal and bone marrow mononuclear stem cells after healed myocardial infarction: an hemodynamic study

info:eu-repo/semantics/nonPublishe

Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1.

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Do maternal cells trigger or perpetuate autoimmune diseases in children?

The placental barrier is not the impenetrable wall that it was once presumed to be. During pregnancy, fetal cells pass into the mother, where they persist for decades after the pregnancy, leading to fetal microchimerism (FMc). Maternal cells also pass into the fetus, where they can persist long after birth of the child into adulthood, leading to maternal microchimerism(MMc). FMc and MMc represent foreign cells, and thus have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. FMc, hypothesized to contribute to the high predisposition of autoimmune diseases in women, has been reviewed recently. In patients who have never been pregnant, (children, males, and nulliparous females), MMc may represent the foreign cells that initiate or perpetuate chronic inflammatory disease