Plasma TGF-<i>β</i>1 Levels Are Elevated in Down Syndrome Infants with Transient Abnormal Myelopoiesis

Abstract

Infants with Down syndrome (DS) are at risk of developing a transient myeloproliferative disorder during the neonatal period, known as transient abnormal myelopoiesis (TAM). It is characterized by clonal myeloproliferation and is typically self-limiting. However, TAM can be a life-threatening disorder, when complicated by liver fibrosis. Here, we evaluated cytokine profiles in two male DS infants having TAM with or without liver dysfunction. The first patient, Patient 1, had hyperleukocytosis with cholestatic liver dysfunction, coagulopathy, and increased counts of blasts and was treated with exchange transfusion (ExT) due to the serious general condition. In Patient 1, serum interleukin (IL)-8 and plasma transforming growth factor (TGF)-β1 levels were markedly elevated before ExT (1,518.2 pg/mL and 17,635 pg/mL, respectively). After ExT, serum IL-8 and plasma TGF-β1 levels decreased to 40.7 pg/mL and 6,847 pg/mL, respectively. However, Patient 1 died on day 56 due to cholestatic liver dysfunction; namely, this patient represents fatal TAM. The second patient, Patient 2, had hyperleukocytosis with increased counts of blasts without liver dysfunction and was treated with cytarabine. In Patient 2, plasma TGF-β1 levels, but not plasma IL-8, were elevated (9,068 pg/mL and 28 pg/mL, respectively). Patient 2 was discharged on day 47. In summary, plasma TGF-β 1 levels were elevated in the two DS infants with TAM, regardless of the presence or absence of hepatic fibrosis. Importantly, fatal TAM is assoicated with the elevated serum level of IL-8. We thus propose that IL-8 may be involved in the pathogenesis of liver fibrosis.

Differential microRNA expression profile in blood of children with Down syndrome suggests a role in immunological dysfunction

“…Moreover, TGF-β regulates the development and functionality of innate cells (dendritic cells, macrophages, granulocytes, and natural killer cells) and the peripheral tolerance against self-antigens [47]. In DS, increased TGF-β levels have been previously associated with transient abnormal myelopoiesis and complications of this condition [48] and pointed as a candidate biomarker for prenatal diagnosis [49].…”

Cytokine Profiles in Pericardial Effusion in a Down Syndrome Infant with Transient Abnormal Myelopoiesis

“…Transforming growth factor (TGF)-β1 is a likely candidate involved in liver fibrogenesis of TAM (Arai et al 1999). And recently Maeda reported that IL-8 was associated with TAM with liver fibrosis (Maeda et al 2016). But these reports did not refer about the association between DS and pericardial effusion.…”

Trastornos mieloproliferativos y leucemia en síndrome de Down. Presentación de dos casos clínicos en el período neonatal

“…2,3 Se estima que entre el 5 % y el 30 % de los neonatos con SD desarrollan MAT, la cual es un trastorno de origen clónico caracterizado por megacarioblastos circulantes y cambios displásicos en las células de sangre periférica. [4][5][6] L a M A T a s o c i a d a a S D ( M A T -S D ) e s t á predispuesta por mutaciones en el gen del factor de transcripción hematopoyético GATA1 y solo se observa junto con la trisomía 21. 3 En la mayoría de los casos, la MAT se resuelve de manera espontánea; sin embargo, la producción de citocinas y la hiperviscosidad, debidas al aumento de blastos y la disfunción inmunológica, causan diversas afecciones.…”