Polymorphisms inTNFandIFNGare associated with clinical characteristics of aplastic anemia in Argentinean population

Abstract

The impaired hematopoiesis in acquired aplastic anemia (AA) results from immune-mediated mechanisms. We characterized polymorphisms implicated in controlling type-1 cytokine production in 69 patients with AA. Our data suggest that the studied polymorphisms are not associated with susceptibility in the overall AA population. However, the presence of the higher expressing TNF - 308A allele was associated with younger age (p = 0.0297) and more profound neutropenia (p = 0.0312), and over-represented in patients with very severe AA (p = 0.0168). The higher producing IFNG 12 CA-repeat allele showed strong linkage disequilibrium with the + 874T allele, and was associated with a lower hemoglobin level (p = 0.0351). Also, the presence of at least one higher expressing variant was more frequent among patients responding to immunosuppressive treatment (p = 0.0519). Our findings suggest that the presence of higher expressing variants of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in AA patient genotypes could be related to clinical parameters, disease severity and therapy outcomes.

Prognostic value of TNF-a-308 and IFN-g-874 single nucleotide polymorphisms and their plasma levels in patients with aplastic anemia

“…No association was recorded in both the inflammatory cytokines after IST between AA and with those of control. Our results are in disagreement with previous reports that showed an association after IST [23,24].…”

TNF-α-induced programmed cell death in the pathogenesis of acquired aplastic anemia

“…Espinoza et al [94] reported that Antimoesin antibodies derived from AA patients can stimulate monocytic cells to secrete TNF-a through the activation of the ERK1/2 pathway provoked by direct binding to moesin. A recent study suggests that the high level TNF-a variants in AA patients is associated with clinical features, disease severity and therapy outcomes [95].…”

Advances in understanding the pathogenesis of acquired aplastic anaemia

“…Indirectly, IFNG acts on IFNG receptor‐expressing macrophages and stromal cells, that in turn may affect stem cell quiescence and exert a pull towards producing progenitor cells (Smith et al , ). A polymorphic site in the IFNG gene may increase susceptibility to developing AA, as well as its severity (Bestach et al , ), and may influence response to IST (Zeng et al , ). AA develops in mice genetically modified to express constitutively low levels of IFNG (Lin et al , ).…”