Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus

Lynne E. Nield, Ingo von Both, Najla Popel, Kate Strachan, Cedric Manlhiot, Patrick Shannon, Brian W. McCrindle, Adelle Atkinson, Steven E.S. Miner, Edgar T. Jaeggi, Glenn P. Taylor

Research output: Contribution to journalArticle

Abstract

The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium. Of 60 fetal autopsy cases identified from institutional databases, 10 had aDCM (18–38 weeks), 12 iDCM (19–37 weeks) and 38 had normal hearts (11–40 weeks). Paraffin-embedded myocardium sections were stained for all lymphocyte (CD45), B cells (CD20, CD79a), T cells (CD3, CD4, CD7, CD8) and monocyte (CD68) surface markers. Two independent, blinded cell counts were performed. Normal hearts expressed all B and T cell markers in a bimodal fashion, with peaks at 22 and 37 weeks of gestation. The aDCM cohort was most distinct from normal hearts, with less overall T cell markers [EST −9.1 (2.6) cells/mm2, p = 0.001], CD4 [EST −2.0 (0.6), p = 0.001], CD3 [EST −3.9 (1.0), p < 0.001], CD7 [EST −3.0 (1.1), p = 0.01] overall B cell markers [EST −4.9 (1.8), p = 0.01] and CD79a counts [EST −2.3 (0.9), p = 0.01]. The iDCM group had less overall B cell markers [EST −4.0 (1.8), p = 0.03] and CD79a [EST −1.7 (0.9), p = 0.05], but no difference in T cell markers. Autoimmune-mediated DCM fetuses have less B and T cell markers, whereas iDCM fetuses have less B cell markers compared with normal fetal hearts. The fetal immune system may play a role in the normal development of the heart and evolution of dilated cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)353-363
Number of pages11
JournalPediatric Cardiology
Volume37
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Keywords

  • Cardiomyopathy
  • Endocardial fibroelastosis
  • Fetus
  • Immune system
  • Myocardium

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Cardiology and Cardiovascular Medicine

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    Nield, L. E., von Both, I., Popel, N., Strachan, K., Manlhiot, C., Shannon, P., McCrindle, B. W., Atkinson, A., Miner, S. E. S., Jaeggi, E. T., & Taylor, G. P. (2016). Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus. Pediatric Cardiology, 37(2), 353-363. https://doi.org/10.1007/s00246-015-1284-4