Submit a comment
Abstract
BACKGROUND Cellular stressors influence the development of clonal hematopoiesis (CH). We hypothesized that environmental, inflammatory, and genotoxic stresses drive the emergence of CH in lung transplant recipients. METHODS We performed a cross-sectional cohort study of 85 lung transplant recipients to characterize CH prevalence. We evaluated somatic variants using duplex error-corrected sequencing and germline variants using whole exome sequencing. We evaluated CH frequency and burden using χ2 and Poisson regression, and we evaluated associations with clinical and demographic variables and clinical outcomes using χ2, logistic regression, and Cox regression. RESULTS CH in DNA damage response (DDR) genes TP53, PPM1D, and ATM was increased in transplant recipients compared with a control group of older adults (28% versus 0%, adjusted OR [aOR], 12.9 [1.7–100.3], P = 0.0002). Age (OR, 1.13 [1.03–1.25], P = 0.014) and smoking history (OR 4.25 [1.02–17.82], P = 0.048) were associated with DDR CH. Germline variants predisposing to idiopathic pulmonary fibrosis were identified but not associated with CH. DDR CH was associated with increased cytomegalovirus viremia versus patients with no (OR, 7.23 [1.95–26.8], P = 0.018) or non-DDR CH (OR, 7.64 [1.77–32.89], P = 0.024) and mycophenolate discontinuation (aOR, 3.8 [1.3–12.9], P = 0.031). CONCLUSION CH in DDR genes is prevalent in lung transplant recipients and is associated with posttransplant outcomes including cytomegalovirus activation and mycophenolate intolerance. FUNDING NIH/NHLBI K01HL155231 (LKT), R25HL105400 (LKT), Foundation for Barnes-Jewish Hospital (LKT), Evans MDS Center at Washington University (KAO, MJW), ASH Scholar Award (KAO), NIH K12CA167540 (KAO), NIH P01AI116501 (AEG, DK), NIH R01HL094601 (AEG), and NIH P01CA101937 (DCL).
Authors
Laneshia K. Tague, Karolyn A. Oetjen, Anirudh Mahadev, Matthew J. Walter, Hephzibah Anthony, Daniel Kreisel, Daniel C. Link, Andrew E. Gelman
Guidelines
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.
- Comments appear on the Journal’s website and are linked from the original article’s web page.
- Authors are notified by email if their comments are posted.
- The Journal reserves the right to edit comments for length and clarity.
- No appeals will be considered.
- Comments are not indexed in PubMed.
Specific requirements
- Maximum length, 400 words
- Entered as plain text or HTML
- Author’s name and email address, to be posted with the comment
- Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
- Comments may not include figures
