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

Abstract

Infants with Down Syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM is characterised by increased circulating blast cells but usually self-limiting. DS patients with TAM sometimes show fetal hydrops and effusion in body cavities, but the mechanism remains unclear. We report here a case of infant with DS who had pericardial effusion, TAM, and eosinophilia. In her pericardial effusion, white blood cell count was 6.0 × 10 3 /µL, 41% of which were eosinophils. After administration of prednisolone, pericardial effusion gradually decreased, and TAM and eosinophilia improved. In order to elucidate the immunological mechanism, we measured the levels of 17 cytokines in her pericardial effusion fluid and serum. In her pericardial fluid, there were high levels of 12 cytokines, and they were higher than those in her serum. In particular, IL-6 (44,573 pg/mL), IL-8 (4,865 pg/mL), and IL-13 (579.41 pg/mL) were at extremely high levels in her pericardial fluid. After administration of prednisolone, the levels of 8 of the 12 elevated cytokines in her pericardial fluid decreased and all of the elevated cytokines decreased in her serum. Corticosteroids can be effective to reduce cytokine levels and the amount of effusion in patients with DS. It is presumed that effusion seen in DS with TAM could be related to an abnormal production of cytokines at the effusion site.

Transient abnormal myelopoiesis with pericardial effusion in Down syndrome: Case report

“…In Table , we summarize the literature reports of patients with DS‐ and TAM‐associated PE. From the reported cases, three cases presented an increased number of eosinophils in the PE, and in two cases, there are no mentions of the cytological aspects of PE …”

“…Kusanagi et al suggest that eosinophilic infiltration at the cardiac site may have caused direct heart damage and failure or that the degranulation of the eosinophils caused PE and consequent cardiomegaly. In the investigation of possible immunological bases for the development of effusion, Shitara et al did not observe a correlation between the increased levels of proinflammatory cytokines in the fluid when compared to the serum. The authors concluded that tumor necrosis factor‐alpha (TNF‐α) and interleukin‐6 (IL‐6) could be involved in fluid retention by increasing the vascular permeability, whereas interleukin‐13 (produced by Th2 lymphocytes) may have played a role in the increase and recruitment of eosinophils into the pericardial fluid.…”

Fetal/Neonatal Pericardial Effusion in Down's Syndrome: Case Report and Review of Literature

“… 10 It is also presumed that effusion could be related to an abnormal production of cytokines at the effusion site. 6 PE has been demonstrated to be in association with hypothyroidism and celiac disease in early childhood 3 14 15 16 but not in the perinatal period. Our case had both TMD and hypothyroidism.…”

“…TMD develops in 3 to 10% of newborns with DS, 5 is characterized by clonal proliferation of blast cells in blood/bone marrow and may be responsible for pericardial effusion. 1 2 4 6 7 8 9 10 11 12 13 Pericardial effusion in TMD may occur due to myocardial infiltration by degranulating eosinophils 13 or epicardial infiltration by atypical myeloid cells. 10 It is also presumed that effusion could be related to an abnormal production of cytokines at the effusion site.…”

“…Our case was diagnosed at 20weeks GA and was monitored in utero. The others 1 6 8 9 10 12 13 have diagnosed them at 30 to36 weeks GA. Two cases were diagnosed in neonatal period (2 weeks) as one of them had no antenatal care 4 and the authors have not reported about antenatal screening in other case. 7 Al-Kasim et al 11 have reported six cases of PE, all diagnosed within 2 weeks of birth at full term gestation except one who was diagnosed at 35 weeks.…”