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

Results From the Multicenter IPAC Study

Charles F. McTiernan, Penelope Morel, Leslie T Jr. Cooper, Navin Rajagopalan, Vinay Thohan, Mark Zucker, John Boehmer, Biykem Bozkurt, Paul Mather, John Thornton, Jalal K. Ghali, Karen Hanley-Yanez, James Fett, Indrani Halder, Dennis M. McNamara

Research output: Contribution to journalArticle

2 Citations (Scopus)

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)
JournalJournal of Cardiac Failure
DOIs
StateAccepted/In press - Jan 1 2017

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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

Keywords

  • Cardiomyopathies
  • Cellular immunity
  • Flow cytometry
  • Peripartum period

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy : Results From the Multicenter IPAC Study. / McTiernan, Charles F.; Morel, Penelope; Cooper, Leslie T Jr.; Rajagopalan, Navin; Thohan, Vinay; Zucker, Mark; Boehmer, John; Bozkurt, Biykem; Mather, Paul; Thornton, John; Ghali, Jalal K.; Hanley-Yanez, Karen; Fett, James; Halder, Indrani; McNamara, Dennis M.

In: Journal of Cardiac Failure, 01.01.2017.

Research output: Contribution to journalArticle

McTiernan, CF, Morel, P, Cooper, LTJ, Rajagopalan, N, Thohan, V, Zucker, M, Boehmer, J, Bozkurt, B, Mather, P, Thornton, J, Ghali, JK, Hanley-Yanez, K, Fett, J, Halder, I & McNamara, DM 2017, 'Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study', Journal of Cardiac Failure. https://doi.org/10.1016/j.cardfail.2017.10.012
McTiernan, Charles F. ; Morel, Penelope ; Cooper, Leslie T Jr. ; Rajagopalan, Navin ; Thohan, Vinay ; Zucker, Mark ; Boehmer, John ; Bozkurt, Biykem ; Mather, Paul ; Thornton, John ; Ghali, Jalal K. ; Hanley-Yanez, Karen ; Fett, James ; Halder, Indrani ; McNamara, Dennis M. / Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy : Results From the Multicenter IPAC Study. In: Journal of Cardiac Failure. 2017.
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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.",
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T1 - Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy

T2 - Results From the Multicenter IPAC Study

AU - McTiernan, Charles F.

AU - Morel, Penelope

AU - Cooper, Leslie T Jr.

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.

PY - 2017/1/1

Y1 - 2017/1/1

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.

KW - Cardiomyopathies

KW - Cellular immunity

KW - Flow cytometry

KW - Peripartum period

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