Elsevier

Clinical Immunology

Volume 212, March 2020, 108247
Clinical Immunology

Brief Communication
Hypertension: An immune related disorder?

https://doi.org/10.1016/j.clim.2019.108247Get rights and content

Highlights

  • IgG, IgA, IgM and C3 serum levels were significantly increased in hypertensive patients compared to healthy controls.

  • Significant decrease in peripheral blood CD3+, CD4+ and CD8+ cells in hypertensives versus healthy subjects was observed.

  • Negative correlations between homocysteine levels along with CD4+ and CD8+ numbers were detected in all study participants.

Abstract

Hypertension is a multifactorial disorder with serious complications and unknown etiology. Among potential contributors, immune dysregulation has been also proposed. The study population included 61 consecutive hypertensive patients and 55 healthy individuals of similar age and sex distribution. All study participants underwent a thorough evaluation for subclinical atherosclerosis. A full immunological profile including quantification of immunoglobulins (IgG, IgM, IgA) and lymphocyte subpopulations was also obtained. Immunoglobulin levels IgG, IgA and IgM and complement factor C3 were found to be significantly increased in the hypertensive compared to the HC group while a statistically significant decrease in peripheral blood CD3+, CD4+ and CD8+ in hypertensive patients versus controls was detected. These findings might support a putative involvement of altered cellular and humoral immune responses in the pathogenesis of hypertension, implying a promising role for immunomodulatory strategies, already implemented in the treatment of autoimmune diseases, in the future management of hypertension.

Introduction

Hypertension defined as chronically raised blood pressure of >140/90 mmHg is a multifactorial disorder with serious adverse outcomes including among others cardiovascular disease and chronic renal injury, posing a global threat in human health [1]. Despite the unprecedented progress in the management of hypertension over the last decades, the underlying mechanisms involved are not fully elucidated. Nevertheless, chronic inflammation and adaptive immune mechanisms are increasingly appreciated as crucial determinants [2] with immunosuppressive agents displaying antihypertensive actions [3].

Interactions between cardiac pump function, vascular resistance and regulation of blood volume by the renal system have been long recognized as the main determinants of systemic blood pressure. Though a mechanistic model between immune pathways activation and deranged physiological action of the key organ systems involved in blood pressure regulation is not entirely clear, a growing body of data supports such as link. Thus, deposition of agonistic antibodies against β1 and α1 adrenergic receptors promote acceleration of cardiac rhythm and vasoconstriction respectively. Constriction of blood vessels can be also mediated by autoantibodies against angiotensin II receptor, while IgG containing immunocomplexes can further result to heightened peripheral resistance and stiffness of the vessel wall through endothelial dysfunction, vascular remodeling and fibrosis upon ligation with Fcγ receptors on endothelial cells [4]. Finally, chronic inflammatory burden seems to also contribute to hypertension pathogenesis since increased levels of IL-6, TNF-α and soluble adhesion molecules have been associated with hypertension in apparently healthy individuals [5], while cytotoxic T lymphocytes have been shown to be activated in kidneys of hypertensive animal models [6]. To this end, integrative network analysis revealed variations of the gene encoding SH2B adaptor protein 3 – a molecule shown to modulate T cell function- to increase susceptibility to hypertension [7].

The aim of the current study was to investigate comprehensively whether aberrant humoral and cellular immune responses are implicated in hypertension.

Section snippets

Study population

The study population included 61 consecutive hypertensive patients [1] followed in the hypertension clinic of the Department of Clinical Therapeutics of “Alexandra Hospital”, National and Kapodistrian University of Athens, Athens, Greece and 55 healthy subjects of similar age/sex distribution with no history of arterial hypertension and blood pressure at entry <135/85 mmHg. Individuals with a history of autoimmune disease, recent infection or surgery (last 3 months), congestive heart failure or

Demographics, traditional risk factors and markers of subclinical atherosclerosis in hypertensive patients and healthy controls

As shown in Supplementary Table 1, significantly increased systolic and diastolic blood pressure values along with higher glucose, total cholesterol and homocysteine levels were observed in hypertensive patients compared to controls. No significant differences were detected in carotid IMT values between patients and controls. In the hypertensive group, the prevalence of diabetes was 13.1% compared to 1.8% in the control group (data not shown).

Humoral and cellular markers in hypertensive patients and controls

Immunoglobulin levels IgG, IgA and IgM and

Discussion

Though atherosclerosis has been long considered a chronic inflammatory disease with immune abnormalities playing a central role, data on the immune involvement in the setting of hypertension is rather limited. In the present study we revealed aberrations in both humoral and cellular immunity arms in hypertensive individuals compared to controls with evidence of polyclonal B cell activation expressed as an increase in serum immunoglobulins together with a reduction of T cell subpopulations in

Declration of Competing Interest

Nothing to declare

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