Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.853403
Keywords
hypertension; aldosterone-producing adenoma (APA); high-throughput sequencing; T-cell receptor (TCR); TCR repertoire; Taiwan Primary Aldosteronism Investigation (TAIPAI)
Categories
Funding
- Ministry of Science and Technology, Taiwan [106-2314-B-002-166-MY3, 107-2314-B-002-026-MY3, 106-2321-B-182-002, 105-2628-B-038-001-MY4, 109-2628-B-038-012, MOST 110-2321-B-038-002]
- National Taiwan University Hospital [105-S3061, 107-S3809, UN103-082, UN106-014, 105-P05, 106-P02, 107-T02]
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This study demonstrates that patients with aldosterone-producing adenoma (APA) have reduced T-cell immune repertoire diversity and exhibit differences compared to patients with hypertension. The study also reveals a stronger correlation between T-cell receptor (TCR) clonotype generation probabilities and frequencies in the APA group. Clinical features are positively associated with the strength of correlation between TCR clonotype generation and abundance in the APA group.
Aldosterone-producing adenoma (APA) is a benign adrenal tumor that results in persistent hyperaldosteronism. As one major subtype of primary aldosteronism, APA leads to secondary hypertension that is associated with immune dysregulation. However, how the adaptive immune system, particularly the T-cell population, is altered in APA patients remains largely unknown. Here, we performed TCR sequencing to characterize the TCR repertoire between two age-matched groups of patients: one with APA and the other one with essential hypertension (EH). Strikingly, we found a significant reduction of TCR repertoire diversity in the APA group. Analyses on TCR clustering and antigen annotation further showed that the APA group possessed lower diversity in TCR clonotypes with non-common antigen-specific features, compared with the EH group. In addition, our results indicated that the strength of correlation between generation probabilities and frequencies of TCR clonotypes was significantly higher in the APA group than that in the EH group. Finally, we observed that clinical features, including plasma aldosterone level, aldosterone-renin ratio, and blood sodium level, were positively associated with the strength of correlation between generation and abundance of TCR clonotypes in the APA group. Our findings unveiled the correlation between T-cell immune repertoire and APA, suggesting a critical role of such adrenal adenoma in the T-cell immunity of patients with hypertension.
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