A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?

Abstract

Bicuspid valve disease is associated with the development of thoracic aortic aneurysm. The molecular mechanisms underlying this association still need to be clarified. Here, we evaluated the circulating levels of T and B lymphocyte subsets associated with the development of vascular diseases in patients with bicuspid aortic valve or tricuspid aortic valve with and without thoracic aortic aneurysm. We unveiled that the circulating levels of the MAIT, CD4+IL−17A+, and NKT T cell subsets were significantly reduced in bicuspid valve disease cases, when compared to tricuspid aortic valve cases in either the presence or the absence of thoracic aortic aneurysm. Among patients with tricuspid aortic valve, these cells were higher in those also affected by thoracic aortic aneurysm. Similar data were obtained by examining CD19+ B cells, naïve B cells (IgD+CD27−), memory unswitched B cells (IgD+CD27+), memory switched B cells (IgD−CD27+), and double-negative B cells (DN) (IgD−CD27−). These cells resulted to be lower in subjects with bicuspid valve disease with respect to patients with tricuspid aortic valve. In whole, our data indicate that patients with bicuspid valve disease show a quantitative reduction of T and B lymphocyte cell subsets. Future studies are encouraged to understand the molecular mechanisms underlying this observation and its pathophysiological significance.

The bicuspid aortic valve: Is it an immunological disease process?

“…The lowest levels seen in the T‐cell subsets examined were that of mucosal‐associated invariant T cells and natural killer T cells . For the B‐cell subsets the lowest levels were seen in CD19+ cells, naïve B IgD+ CD27− cells, IgD+ CD27+ cells (memory switched and unswitched) and double negative B cells . This B and T lymphocyte profile reflects what has been observed in older people, so the study suggests BAV patients seem to have an “old immune system” with an increased inflammatory component, which is more vulnerable to internal and external stressors, frailty, disability, and disease .…”

“…They also observed a slightly elevated level of the same subsets in patients with thoracic aortic aneurysm (TAA), a trend seen in both BAV and TAV patients; the only exception to elevated levels in TAA patients was for double negative B cell levels . The lowest levels seen in the T‐cell subsets examined were that of mucosal‐associated invariant T cells and natural killer T cells . For the B‐cell subsets the lowest levels were seen in CD19+ cells, naïve B IgD+ CD27− cells, IgD+ CD27+ cells (memory switched and unswitched) and double negative B cells .…”

“…A study by Balistreti et al in 2018 found that BAV patients had reduced levels of some T and B lymphocyte subsets when compared with TAV patients. They also observed a slightly elevated level of the same subsets in patients with thoracic aortic aneurysm (TAA), a trend seen in both BAV and TAV patients; the only exception to elevated levels in TAA patients was for double negative B cell levels . The lowest levels seen in the T‐cell subsets examined were that of mucosal‐associated invariant T cells and natural killer T cells .…”

Deregulation of TLR4 signaling pathway characterizes Bicuspid Aortic valve syndrome

“…We recently evidenced the presence of distinctive molecular and cellular mechanisms in BAV patients, when compared to tricuspid aortic valve (TAV) patients with or without AAA 11–13 . Specifically, we demonstrated an increased allele frequency of some polymorphisms in genes encoding molecules of NO, MMP, ACE pathways 13 , a quantitative reduction in the circulating levels of T and B lymphocytes cell subsets 14 , a deregulation of Notch 1 pathway and circulating endothelial progenitor cell (EPC) 15 number in BAV cases compared to TAV cases, irrespective from the presence of AAA disease.…”

Changes in inflammation and oxidative stress signalling pathways in coarcted aorta triggered by bicuspid aortic valve and growth in young children

“…Possibly changes in both basal immunological status and in the response to surgery exist. One recent paper found that BAV patients have decreased T and B lymphocyte levels and the authors suggested that BAV patients have ‘an old immune system’ which is ‘more easily vulnerable to internal and external stressors’ ( 31 ).…”