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Pediatr Cardiol. 2016 Feb;37(2):353-63. doi: 10.1007/s00246-015-1284-4. Epub 2015 Oct 20.

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

Author information

1
Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. lynne.nield@sickkids.ca.
2
Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada.
3
University of Toronto, Toronto, ON, Canada.
4
Department of Pathology, Mount Sinai Hospital, Toronto, ON, Canada.
5
Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
6
Division of Immunology and Allergy, The Hospital for Sick Children, Toronto, ON, Canada.
7
Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.

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/mm(2), 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.

KEYWORDS:

Cardiomyopathy; Endocardial fibroelastosis; Fetus; Immune system; Myocardium

PMID:
26481221
DOI:
10.1007/s00246-015-1284-4
[Indexed for MEDLINE]

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