Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy

Results From the Multicenter IPAC Study

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Abstract

Objective The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. Background PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. Methods The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). Results Entry NK cell levels (CD3–CD56+CD16+; reported as % of CD3– cells) were significantly (P <.0003) reduced in PPCM (6.6 ± 4.9% of CD3– cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P <.004) between PPCM (24.5 ± 12.5% of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. Conclusions Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation.

Original languageEnglish (US)
Pages (from-to)33-42
Number of pages10
JournalJournal of Cardiac Failure
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2018

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Peripartum Period
T-Lymphocyte Subsets
Cardiomyopathies
Natural Killer Cells
Monocytes
Pregnancy
Postpartum Period
Maternal Mortality
Regulatory T-Lymphocytes
Cellular Immunity
Stroke Volume
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{a627c7175d00404782a2ca06e101eb78,
title = "Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study",
abstract = "Objective The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. Background PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. Methods The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). Results Entry NK cell levels (CD3–CD56+CD16+; reported as {\%} of CD3– cells) were significantly (P <.0003) reduced in PPCM (6.6 ± 4.9{\%} of CD3– cells) compared to HP (11.9 ± 5{\%}). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P <.004) between PPCM (24.5 ± 12.5{\%} of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4{\%}). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. Conclusions Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation.",
author = "{for the} and McTiernan, {Charles F.} and Penelope Morel and Cooper, {Leslie T.} and Navin Rajagopalan and Vinay Thohan and Mark Zucker and John Boehmer and Biykem Bozkurt and Paul Mather and John Thornton and Ghali, {Jalal K.} and Karen Hanley-Yanez and James Fett and Indrani Halder and McNamara, {Dennis M.} and McNamara, {Dennis M.} and Fett, {James D.} and Jessica Pisarcik and Charles McTiernan and Karen Hanley-Yanez and John Gorcsan and Erik Schelbert and Rami Alharethi and Kismet Rasmusson and Kim Brunisholz and Amy Butler and Deborah Budge and Kfoury, {A. G.} and Benjamin Horne and Joe Tuinei and Heather Brown and Julie Damp and Naftilan, {Allen J.} and Jill Russell and Darla Freehardt and Eileen Hsich and Cynthia Oblak and Greg Ewald and Donna Whitehead and Jean Flanagan and Anne Platts and Uri Elkayam and Jorge Caro and Stephanie Mullin and Givertz, {Michael M.} and Anello, {M. Susan} and Navin Rajagopalan and David Booth and Tiffany Sandlin and Jordan Safirstein",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.cardfail.2017.10.012",
language = "English (US)",
volume = "24",
pages = "33--42",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",
number = "1",

}

TY - JOUR

T1 - Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy

T2 - Results From the Multicenter IPAC Study

AU - for the

AU - McTiernan, Charles F.

AU - Morel, Penelope

AU - Cooper, Leslie T.

AU - Rajagopalan, Navin

AU - Thohan, Vinay

AU - Zucker, Mark

AU - Boehmer, John

AU - Bozkurt, Biykem

AU - Mather, Paul

AU - Thornton, John

AU - Ghali, Jalal K.

AU - Hanley-Yanez, Karen

AU - Fett, James

AU - Halder, Indrani

AU - McNamara, Dennis M.

AU - McNamara, Dennis M.

AU - Fett, James D.

AU - Pisarcik, Jessica

AU - McTiernan, Charles

AU - Hanley-Yanez, Karen

AU - Gorcsan, John

AU - Schelbert, Erik

AU - Alharethi, Rami

AU - Rasmusson, Kismet

AU - Brunisholz, Kim

AU - Butler, Amy

AU - Budge, Deborah

AU - Kfoury, A. G.

AU - Horne, Benjamin

AU - Tuinei, Joe

AU - Brown, Heather

AU - Damp, Julie

AU - Naftilan, Allen J.

AU - Russell, Jill

AU - Freehardt, Darla

AU - Hsich, Eileen

AU - Oblak, Cynthia

AU - Ewald, Greg

AU - Whitehead, Donna

AU - Flanagan, Jean

AU - Platts, Anne

AU - Elkayam, Uri

AU - Caro, Jorge

AU - Mullin, Stephanie

AU - Givertz, Michael M.

AU - Anello, M. Susan

AU - Rajagopalan, Navin

AU - Booth, David

AU - Sandlin, Tiffany

AU - Safirstein, Jordan

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. Background PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. Methods The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). Results Entry NK cell levels (CD3–CD56+CD16+; reported as % of CD3– cells) were significantly (P <.0003) reduced in PPCM (6.6 ± 4.9% of CD3– cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P <.004) between PPCM (24.5 ± 12.5% of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. Conclusions Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation.

AB - Objective The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. Background PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. Methods The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). Results Entry NK cell levels (CD3–CD56+CD16+; reported as % of CD3– cells) were significantly (P <.0003) reduced in PPCM (6.6 ± 4.9% of CD3– cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P <.004) between PPCM (24.5 ± 12.5% of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. Conclusions Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation.

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U2 - 10.1016/j.cardfail.2017.10.012

DO - 10.1016/j.cardfail.2017.10.012

M3 - Article

VL - 24

SP - 33

EP - 42

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

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ER -