Associations between CD70 methylation of T cell DNA and age in adults with systemic lupus erythematosus and population controls: The Michigan Lupus Epidemiology & Surveillance (MILES) Program

Details

• Alternative Title:
  J Autoimmun
• Personal Author:
  Somers, Emily C ; Goodrich, Jaclyn M ; Wang, Lu ; Harlow, Sioban D ; Marder, Wendy ; Hassett, Afton L ; Zick, Suzanna M ; McCune, W Joseph ; Gordon, Caroline ; Barbour, Kamil E ; Helmick, Charles G ; Strickland, Faith M
• Description:
  Background
  
  Environmental factors can influence epigenetic regulation, including DNA methylation, potentially contributing to systemic lupus erythematosus (SLE) development and progression. We compared methylation of the B cell costimulatory CD70 gene, in persons with lupus and controls, and characterized associations with age.
  
  Results
  
  In 297 adults with SLE and 92 controls from the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, average CD70 methylation of CD4+ T cell DNA across 10 CpG sites based on pyrosequencing of the promoter region was higher for persons with SLE compared to controls, accounting for covariates [β=2.3, p=0.011]. Using Infinium MethylationEPIC array data at 18 CD70-annoted loci (CD4+ and CD8+ T cell DNA), sites within the promoter region tended to be hypomethylated in SLE, while those within the gene region were hypermethylated. In SLE but not controls, age was significantly associated with pyrosequencing-based CD70 methylation: for every year increase in age, methylation increased by 0.14 percentage points in SLE, accounting for covariates. Also within SLE, CD70 methylation approached a significantly higher level in Black persons compared to White persons (β=1.8, p=0.051).
  
  Conclusions
  
  We describe altered CD70 methylation patterns in T lymphocyte subsets in adults with SLE relative to controls, and report associations particular to SLE between methylation of this immune-relevant gene and both age and race, possibly a consequence of “weathering” or accelerated aging which may have implications for SLE pathogenesis and potential intervention strategies.
  
  
• Subjects:
  Adult CD4-Positive T-Lymphocytes CD27 Ligand DNA DNA Methylation Epigenesis, Genetic Humans Lupus Erythematosus, Systemic Michigan
• Keywords:
  Aging Autoimmunity CD4+ CD8+ Epidemiology Epigenetics Immunoepidemiology TNFSF7
• Source:
  J Autoimmun. 142:103137
• Pubmed ID:
  38064919
• Pubmed Central ID:
  PMC10957300
• Document Type:
  Journal Article
• Funding:
  U01 DP003250/DP/NCCDPHP CDC HHSUnited States/ ; T32 AR007080/AR/NIAMS NIH HHSUnited States/ ; K01 ES019909/ES/NIEHS NIH HHSUnited States/ ; P30 ES017885/ES/NIEHS NIH HHSUnited States/ ; UL1 TR002240/TR/NCATS NIH HHSUnited States/ ; U01 DP006265/DP/NCCDPHP CDC HHSUnited States/ ; U58 DP001441/DP/NCCDPHP CDC HHSUnited States/ ; U01 DP006489/DP/NCCDPHP CDC HHSUnited States/
• Volume:
  142
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:90e414a11fd06d7434c4382ad35a9d4a045946cb7dc719b4f6f82740670c2b3be2a1397f6a49220424448a3e786de39002b48b03851d458692ea09e82fd33330
• Download URL:
  https://stacks.cdc.gov/view/cdc/153478/cdc_153478_DS1.pdf
• File Type:
  [PDF - 1.24 MB ]