Breastfeeding, Cellular Immune Activation, and Myocardial Recovery in Peripartum Cardiomyopathy

Abstract Introduction Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function. Methods Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF). Results This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2–1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD < 55 mm) and systolic function (LVEF > 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05–0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04–0.89], p = 0.035) at follow-up. Conclusions We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.

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Urinary suPAR: a non-invasive biomarker of infection and tissue inflammation for use in studies of large free-ranging mammals

Royal Society Open Science ◽

10.1098/rsos.191825 ◽

2020 ◽

Vol 7 (2) ◽

pp. 191825 ◽

Cited By ~ 1

Author(s):

James P. Higham ◽

Christiane Stahl-Hennig ◽

Michael Heistermann

Keyword(s):

Immune Activation ◽

Rhesus Macaques ◽

Soluble Form ◽

Surgical Trauma ◽

Large Mammals ◽

Urokinase Plasminogen Activator Receptor ◽

Different Temperatures ◽

Processing And Storage ◽

Cellular Immune ◽

Free Ranging

Studies of large free-ranging mammals incorporating physiological measurements typically require the collection of urine or faecal samples, due to ethical and practical concerns over trapping or darting animals. However, there is a dearth of validated biomarkers of immune activation and inflammation that can be measured non-invasively. We here evaluate the utility of urinary measurements of the soluble form of the urokinase plasminogen activator receptor (suPAR), for use as a health marker in studies of wild large mammals. We investigate how urinary suPAR concentrations change in response to viral infection and surgical trauma (inflammation), comparing it to the measurement of a marker of cellular immune activation, urinary neopterin (uNEO), in captive rhesus macaques. We then test the field utility of urinary suPAR, assessing the effects of soil and faecal contamination, sunlight, storage at different temperatures, freeze–thaw cycles, and lyophilization. We find that suPAR concentrations rise markedly in response to both infection and surgery-associated inflammation, unlike uNEO concentrations, which only rise in response to the former. Our field validation demonstrates that urinary suPAR is reasonably robust to many of the issues associated with field collection, sample processing, and storage, as long as samples can be stored in a freezer. Urinary suPAR is thus a promising biomarker applicable for monitoring various aspects of health in wild primates and potentially also other large mammals.

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A biomimetic yeast shell vaccine coated with layered double hydroxides induces a robust humoral and cellular immune response against tumors

Nanoscale Advances ◽

10.1039/d0na00249f ◽

2020 ◽

Vol 2 (8) ◽

pp. 3494-3506

Author(s):

Dong-qun Liu ◽

Shuai Lu ◽

Lun Zhang ◽

Ling-xiao Zhang ◽

Mei Ji ◽

...

Keyword(s):

Immune Response ◽

Layered Double Hydroxides ◽

Immune Activation ◽

Cellular Immune Response ◽

Cellular Immune ◽

Double Hydroxides

Schematic illustration of the LDH nanoparticle-coated yeast shell vaccine and immune activation.

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Cellular immune activation in the brain and human immunodeficiency virus infection

Annals of Neurology ◽

10.1002/ana.410240227 ◽

1988 ◽

Vol 24 (2) ◽

pp. 289-289 ◽

Cited By ~ 10

Author(s):

Dietmarch Fuchs ◽

Ernst R. Werner ◽

Manfred P. Dierich ◽

Helmut Wachter

Keyword(s):

Human Immunodeficiency Virus ◽

Virus Infection ◽

Human Immunodeficiency Virus Infection ◽

Immune Activation ◽

Immunodeficiency Virus ◽

Cellular Immune ◽

The Brain

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Clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy: an ESC EORP registry

European Heart Journal ◽

10.1093/eurheartj/ehaa455 ◽

2020 ◽

Vol 41 (39) ◽

pp. 3787-3797 ◽

Cited By ~ 3

Author(s):

Karen Sliwa ◽

Mark C Petrie ◽

Peter van der Meer ◽

Alexandre Mebazaa ◽

Denise Hilfiker-Kleiner ◽

...

Keyword(s):

Heart Failure ◽

Middle East ◽

Regional Variation ◽

Clinical Presentation ◽

Left Ventricular ◽

Peripartum Cardiomyopathy ◽

Asia Pacific ◽

Left Ventricular Ejection ◽

Myocardial Recovery ◽

Ventricular Ejection Fraction

Abstract Aims We sought to describe the clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy (PPCM) globally. Methods and results In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global registry on PPCM, under the auspices of the ESC EURObservational Research Programme. These societies were tasked with identifying centres who could participate in this registry. In low-income countries, e.g. Mozambique or Burkina Faso, where there are no national societies due to a shortage of cardiologists, we identified potential participants through abstracts and publications and encouraged participation into the study. Seven hundred and thirty-nine women were enrolled in 49 countries in Europe (33%), Africa (29%), Asia-Pacific (15%), and the Middle East (22%). Mean age was 31 ± 6 years, mean left ventricular ejection fraction (LVEF) was 31 ± 10%, and 10% had a previous pregnancy complicated by PPCM. Symptom-onset occurred most often within 1 month of delivery (44%). At diagnosis, 67% of patients had severe (NYHA III/IV) symptoms and 67% had a LVEF ≤35%. Fifteen percent received bromocriptine with significant regional variation (Europe 15%, Africa 26%, Asia-Pacific 8%, the Middle East 4%, P < 0.001). Follow-up was available for 598 (81%) women. Six-month mortality was 6% overall, lowest in Europe (4%), and highest in the Middle East (10%). Most deaths were due to heart failure (42%) or sudden (30%). Re-admission for any reason occurred in 10% (with just over half of these for heart failure) and thromboembolic events in 7%. Myocardial recovery (LVEF > 50%) occurred only in 46%, most commonly in Asia-Pacific (62%), and least commonly in the Middle East (25%). Neonatal death occurred in 5% with marked regional variation (Europe 2%, the Middle East 9%). Conclusion Peripartum cardiomyopathy is a global disease, but clinical presentation and outcomes vary by region. Just under half of women experience myocardial recovery. Peripartum cardiomyopathy is a disease with substantial maternal and neonatal morbidity and mortality.

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Human Ebola virus infection results in substantial immune activation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1502619112 ◽

2015 ◽

Vol 112 (15) ◽

pp. 4719-4724 ◽

Cited By ~ 177

Author(s):

Anita K. McElroy ◽

Rama S. Akondy ◽

Carl W. Davis ◽

Ali H. Ellebedy ◽

Aneesh K. Mehta ◽

...

Keyword(s):

T Cells ◽

Virus Infection ◽

Immune Responses ◽

Cd8 T Cells ◽

Immune Activation ◽

Ebola Virus ◽

Natural Infection ◽

University Hospital ◽

Cellular Immune ◽

Ebola Virus Infection

Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

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