Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.
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.
Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. lynne.nield@sickkids.ca.
Lynne E
LE
Nield
Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada.
Ingo
I
von Both
University of Toronto, Toronto, ON, Canada.
Najla
N
Popel
Department of Pathology, Mount Sinai Hospital, Toronto, ON, Canada.
Kate
K
Strachan
Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Cedric
C
Manlhiot
Department of Pathology, Mount Sinai Hospital, Toronto, ON, Canada.
Patrick
P
Shannon
Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Brian W
BW
McCrindle
Division of Immunology and Allergy, The Hospital for Sick Children, Toronto, ON, Canada.
Adelle
A
Atkinson
University of Toronto, Toronto, ON, Canada.
Steven E S
SE
Miner
Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Edgar T
ET
Jaeggi
Department of Pathology, Mount Sinai Hospital, Toronto, ON, Canada.|Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
Glenn P
GP
Taylor
D001344:Autopsy; D001402:B-Lymphocytes / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D016022:Case-Control Studies; D016208:Databases, Factual; D005260:Female; D005318:Fetal Heart / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D009864:Ontario; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000166:cytology*
D015415:Biomarkers
Cardiomyopathy; Endocardial fibroelastosis; Fetus; Immune system; Myocardium