To investigate whether DNA methylation patterns in blood are associated with subsequent lymphoma in primary Sjögren's disease (SjD).
Approach:
Study Design: Peripheral blood DNA samples from SjD patients collected between 1998 and 2013 were analyzed using the Illumina HumanMethylation450K BeadChip.
Patient Classification: Six patients who developed lymphoma ≥1 year after blood sampling were classified as SjD sampled pre-lymphoma, and 84 patients without lymphoma as SjD-only.
Data Analysis: Epigenome-wide association analyses were adjusted for age, sex, and estimated blood cell-type proportions, with differentially methylated CpG positions defined by Bonferroni-corrected p≤1.3×10-7 and |Δβ|>0.05.
Key Findings:
A total of 473 autosomal and one X-chromosomal differentially methylated positions (DMPs) distinguished SjD sampled pre-lymphoma from SjD-only, with 87% being hypomethylated in SjD pre-lymphoma.
The most significant DMP mapped to Thymidine kinase 1 (TK1; p=7.6×10-15, Δβ=–0.16).
Functional annotation revealed enrichment for immune activation, leukocyte signaling, and vesicle-mediated secretion pathways.
Patients sampled pre-lymphoma exhibited reduced NK cell and increased monocyte proportions.
Interpretation:
Distinct DNA methylation changes precede lymphoma in SjD, affecting genes involved in immune regulation, cytotoxic function, and proliferation.
Limitations:
The study is exploratory and requires replication.
Conclusion:
The study is exploratory and requires replication.
