Inflammatory and immune checkpoint markers are associated with the severity of aortic stenosisCentral MessagePerspective
Bilguun Erkhem-Ochir, MD,
Wataru Tatsuishi, MD, PhD,
Takehiko Yokobori, MD, PhD,
Tsukasa Ohno, MD, PhD,
Kyohei Hatori, MD, PhD,
Tadashi Handa, PhD,
Tetsunari Oyama, MD, PhD,
Ken Shirabe, MD, PhD,
Hiroshi Saeki, MD, PhD,
Tomonobu Abe, MD, PhD
Affiliations
Bilguun Erkhem-Ochir, MD
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
Wataru Tatsuishi, MD, PhD
Division of Cardiovascular Surgery, Department of General Surgical Science, Gunma University, Maebashi, Gunma, Japan
Takehiko Yokobori, MD, PhD
Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma, Japan; Address for reprints: Takehiko Yokobori, MD, PhD, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), 3-39-22 Showa-machi, Maebashi 371-8511, Japan.
Tsukasa Ohno, MD, PhD
Division of Cardiovascular Surgery, Department of General Surgical Science, Gunma University, Maebashi, Gunma, Japan
Kyohei Hatori, MD, PhD
Division of Cardiovascular Surgery, Department of General Surgical Science, Gunma University, Maebashi, Gunma, Japan
Tadashi Handa, PhD
Department of Diagnostic Pathology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan; Department of Social Welfare, Gunma University of Health and Welfare, Maebashi, Gunma, Japan
Tetsunari Oyama, MD, PhD
Department of Diagnostic Pathology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
Ken Shirabe, MD, PhD
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
Hiroshi Saeki, MD, PhD
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
Tomonobu Abe, MD, PhD
Division of Cardiovascular Surgery, Department of General Surgical Science, Gunma University, Maebashi, Gunma, Japan
Objective: Aortic stenosis (AS) is a disease characterized by narrowing of the aortic valve (AV) orifice. In relation to this disease, the purpose of this study was to elucidate the relationships among factors such as expression of programmed cell death-1 ligand (PD-L1, which is the ligand of PD-1 protein; together, they play a central role in the inhibition of T lymphocyte function), clinicopathologic characteristics, infiltrating immune cells, and disease severity. Methods: We performed immunohistochemical analysis on the surgically-resected AVs of 53 patients with AS. We used the resultant data to identify relationships among PD-L1 expression, disease severity, and the infiltration of immune cells including cluster of differentiation (CD8)-positive T lymphocytes, cluster of differentiation 163 (CD163)-positive macrophages, and forkhead box protein 3 (FOXP3)-positive regulatory T lymphocytes (Tregs). Results: PD-L1 expression in resected AVs was significantly associated with being nonsmoker, valve calcification, and the infiltration of CD8-positive T cells and CD163-positive macrophages. Disease severity and valve calcification were significantly associated with low infiltration of FOXP3-positive Tregs and high infiltration of CD8-positive T cells and CD163-positive macrophages. Moreover, calcified AVs with high PD-L1 expression showed active inflammation without FOXP3-positive Tregs but with high levels of CD8-positive T lymphocytes and CD163-positive macrophages. Conclusions: Immune cell infiltration in the AVs and expression of the immune checkpoint protein PD-L1 were associated with the calcification of AS and disease severity.
