FEATURES OF IMMUNITY IN PATIENTS WITH CHRONIC HEART FAILURE
SHHE “Ivano-Frankivsk National Medical
врожденного иммунитета изучены в 389 больных из сердечной недостаточностью (СН)
ишемического генеза. СН характеризуется снижением фагоцитарной активности
нейтрофилов, увеличением уровня в сыворотке крови патологических мелко- и
среднемолекулярных циркулирующих иммунных комплексов на фоне снижения
физиологических крупномолекулярных ЦИК. Таким образом, у пациентов с
ишемической сердечной недостаточностью присутствуют нарушения врожденного
иммунитета, которые поддерживают хроническое воспаление.
Ключевые слова: сердечная недостаточность, врожденный иммунитет
It’s known, that 18 million deaths annually worldwide are attributed to cardiovascular diseases .
According to results of Prospective
Urban Rural Epidemiologic (PURE) cohort study, which involved
more than 150,000 adults in different economics levels countries, the rates of major cardiovascular events (death from
cardiovascular causes, myocardial infarction, stroke, or heart failure) were
lower in high-income countries than in middle- and low-income countries (3.99
events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years,
respectively; P<0.001). Case fatality rates were also lowest in high-income
countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries,
respectively; P=0.01) .
Heart failure (HF) is the end
stage of most diseases of the cardiovascular system and is a major cause of
morbidity and mortality. About 26 million adults worldwide are living with HF,
leading some to describe it as a global pandemic . Coronary artery disease
(CAD) is the main reason of HF.
An inﬂammatory activation
in HF patients has long been recognized. Indeed, immune mechanisms modulate
interstitial ﬁbrosis, cardiomyocyte apoptosis, and hypertrophy, all of
which are central processes leading to maladaptive remodeling in response to a
variety of stimuli (ischemia, glucose intolerance, obesity, pressure overload
etc.). Especially for heart failure evolving from large myocardial infarction
there is substantial evidence for a causal contribution of immunity early in
the course of the disease .
The immune system of humans
consists of two components: the innate and adaptive immunity. While the
adaptive immune system relies on somatically generated and clonally selected
antigen receptors, the innate immune system detects the presence of pathogens
by their evolutionarily highly conserved, relatively invariant structural
motifs. Various components of the innate immune system are activated in cardiac
diseases without direct involvement of infectious pathogens. For example, a
number of infammatory cytokines, including TNF (tumor necrosis factor), IL
(interleukin)-1β, IL-6 and IL-8, as well as iNOS (inducible nitric oxide
synthase), all components of innate immunity, are increased after
cardiac injury. Moreover, they are all functionally implicated in ischemia/reperfusion
injury, and in the abnormal myocardial remodeling characteristic of advanced
congestive heart failure. Additionally, downstream targets of these proteins,
the transcription factors nuclear factor kappa B (NF-κB) and activator
protein 1 (AP-1), are activated in cardiac injury .
The data of experimental and
clinical trials for innate immunity values in patients with HF are poor.
The purpose of study was to
evaluate of innate immunity parameters in patients with ischemic heart failure.
Material and Methods. We
observed of 389 patients with HF II-IV FC (NYHA). The diagnosis was verified by
laboratory and instrumental methods according to European Society of Cardiology
recommendations (2013, 2014). 30 apparently healthy persons were included into
control group. We studied of functional activity of T-cells by using of blast
transformation reaction test (LBT): spontaneous and stimulated by
phytohemagglutinin ; phagocytic
activity of neutrophils was detected by using of phagocytic index and
phagocytic count . The level of circulating immune complexes in serum was
detected by precipitation methods with polyethylenglycol of different molecular
The study was performed in
accordance with the Helsinki Declaration and Good Clinical Practice Guideline. The study was approved by the local ethics committee and
written informed consent was
obtained from all patients. Statistical analyses were performed using
the Statistica 12.0 (StatSoft, Tulsa, OK, USA). Statistical significance was
assumed at p<0.05.
Results and Discussion. In
cohort of observed patients with HF and sinus rhythm 89 (22.88 %) were
females. The middle age was (69.04±10.99)
years. ІI – nd
FC of HF (NYHA)
was verified in 64
patients with sinus rhythm (16.45 %); ІІІ-rd – in 258 (66.33 %); IV-th – in 67 (17.22 %). 277 (71.21 %)
had history of myocardial infarction (MI). Among them 27 patients (10.49 %) had history of recurrent MI.
In patients with HF the
functional activity of immune cells had some changes. In particular, the value of
spontaneous LBT test were same in HF patients and healthy persons groups (p>0.05). But,
the average values of stimulated LBT test was higher for 18.7% in HF group (p<0.05).
HF caused of phagocytic activity of neutrophils
decline. In these patients we observed decrease of phagocytic index for 11.9% (p<0,05) and
phagocytic count for 68.9% (p<0,05).
It should be noted, that in
observed patients with ischemic HF the increase of neutrophils number in blood
accompanied by decrease of their functional activity. For our opinion, it could
be sign of immunodeficiency.
The syndrome of HF caused of
circulating immune complexes (CIC) dysbalance. In particular, the level of
physiological high-molecular CIC was lower for 1.74 times compared control
group (p<0.01). Simultaneously, the serum concentration of
pathological middle-molecular CIC was higher for 1.53 times (p<0.01), and
low-molecular CIC – for 3.58 times compared control values (p<0.01).
The elevation of high
pathological CIC accompanied with phagocytic activity of neutrophils decline,
that caused to their elimination disturbance. These CIC blocks of CD2 and CD3
receptors on T-cells surface which resulted to complement system activation for
alternative pathway. This process supports of chronic inflammation.
in patients with ischemic heart failure the innate immunity disturbances are
present which caused to chronic inflammation support.
The perspective of future
investigations is study of adaptive immunity changes in patients with HF.
1. Murray C.J.L., Vos T., Lozano R., et al. Disability-adjusted life years (DALYs) for 291
diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the
Global Burden of Disease Study 2010. Lancet
2. Yusuf S., Rangarajan S., Teo K. et al.
Cardiovascular Risk and Events in 17 Low-, Middle-, and High-Income Countries.
A.P., Fonarov G.C., Butler
J. et al. The global health and economic burden of hospitalizations for heart
failure: lessons learned from HHF registres. J. Am. Coll. Cardiol. 2014; 63:
4. Hofmann U., Frantz S. How we can
cure a heart “in flame”? A translation view on inflammation in heart failure.
Basic. Res. Cardiol. 2013; 108: 2-19.
S., Ertil G., Bauersachs J. Innate immunity in heart failure. Nova Acta
Leopoldina. 2008; 351: 17-20.
P., Zawodniak A., Pichler W. J. In Vitro tests in drug hypersensitivity
diagnosis. Immunology and Allergy Clinics of North America.
2009; 29: 537–554.
Panasiuk A., Wysocka J., Maciorkowska E. et
al. Phagocytic and oxidative burst activity of neutrophils in the end stage of
liver cirrhosis. 2005; 11: 7661-7665.