Reduced Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients With Essential Hypertension and Subclinical Carotid Atherosclerosis

Abstract

BACKGROUND: It has long been hypothesized that the abnormal immune responses contribute to the essential hypertension (EH) and its subclinical target organ damage (STOD). However, the mechanism is unclear. This study aimed at exploring the potential association with abnormal T-cell responses and EH, STOD, and early atherosclerosis in patients with EH. METHODS: This cross-sectional study included 146 patients with EH and 73 age-matched normotensive individuals. The expressed peripheral TCR (T-cell receptor) β repertoire was analyzed by high through-put sequencing. RESULTS: The TCRβ repertoires of the patients with EH were significantly different, with significantly elevated certain TCR beta variable ( TRBV ) and joint ( TRBJ ) gene usages, significantly reduced TCRβ diversity indexes (diversity 50s) and numbers of total TCRβ clonal types, significantly elevated percentages of the biggest TCRβ clones and numbers of clones accounting >0.1% sequences, compared with those in the normotensive controls. Decreased diversity 50s and increased biggest TCRβ clone percentages were independently correlated with carotid intima-media thickness and subclinical carotid atherosclerosis (SCA) in the patients with EH. Moreover, the diversity 50s were further significantly reduced and the biggest TCRβ clone percentages were significantly increased in the patients with EH with SCA (n=89) comparing to the patients with EH/patients without SCA (n=57), and in patients with EH/SCA with carotid plaque (n=22) comparing to patients with EH/SCA/patients without carotid plaque (n=67). Importantly, specific TCRβ clones were identified in different subgroups of the patients with EH. CONCLUSIONS: These results reveal that abnormal T-cell responses may play important roles in the progression of EH and its SCA, especially the formation of carotid plaque. REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR2100054414.

TCR-Sequencing Provides a Barcode of Immune Activation and Target Organ Damage in Human Hypertension

“…As a further example, it has been shown that patients with EH or hypertension due to secondary causes like aldosterone-producing adenoma display a different type of TCR repertoire. 15 Ma et al 13 found a positive correlation between reduced T cell clone diversity and the number of antihypertensive drugs taken. This information could be related to the fact that patients with enhanced immune activation might have severe hypertension and, consequently, assume more drugs.…”

“…12 In particular, high-throughput sequencing of the TCR provided valuable information on the computational landscape of T cell repertoire in relation to disease status. 12 In this issue, Ma et al 13 utilized high-throughput sequencing to analyze the peripheral TCR repertoire in patients with essential hypertension (EH) and evaluate the potential contribution of T cell response to disease progression. The authors evaluated the peripheral TCRβ (T cell receptor β-chain) clones in the peripheral blood mononuclear cells isolated from a considerable number of patients with EH (n=146) and normotensive subjects (n=73).…”

“…Ma et al 13 found a positive correlation between reduced T cell clone diversity and the number of antihypertensive drugs taken. This information could be related to the fact that patients with enhanced immune activation might have severe hypertension and, consequently, assume more drugs.…”