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Pediatric Cardiology

, Volume 37, Issue 2, pp 353–363 | Cite as

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

  • Lynne E. NieldEmail author
  • 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
Original Article

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.

Keywords

Immune system Cardiomyopathy Myocardium Fetus Endocardial fibroelastosis 

Abbreviations

iDCM

Idiopathic dilated cardiomyopathy

aDCM

Autoimmune-associated dilated cardiomyopathy

EFE

Endocardial fibroelastosis

LV

Left ventricle

RV

Right ventricle

Notes

Acknowledgments

We would also like to thank Geraldine Garcia, Roseline Dunst and Susan Cromwell who helped with identifying and staining the cases.

Funding

This study was funded by the Labatt Family Innovations Fund research grant.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Lynne E. Nield
    • 1
    Email author
  • Ingo von Both
    • 2
  • Najla Popel
    • 3
  • Kate Strachan
    • 4
  • Cedric Manlhiot
    • 1
  • Patrick Shannon
    • 4
  • Brian W. McCrindle
    • 1
  • Adelle Atkinson
    • 5
  • Steven E. S. Miner
    • 3
  • Edgar T. Jaeggi
    • 1
  • Glenn P. Taylor
    • 4
    • 6
  1. 1.Division of Cardiology, Labatt Family Heart CentreThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Department of Pathobiology and Laboratory MedicineUniversity of TorontoTorontoCanada
  3. 3.University of TorontoTorontoCanada
  4. 4.Department of PathologyMount Sinai HospitalTorontoCanada
  5. 5.Division of Immunology and AllergyThe Hospital for Sick ChildrenTorontoCanada
  6. 6.Division of PathologyThe Hospital for Sick ChildrenTorontoCanada

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