Kidney Week

Abstract: TH-PO573

Blood DNA Methylation Is Associated with Histopathological Changes in Patients with Lupus Nephritis

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Bakhoum, Christine Y., Yale University School of Medicine, New Haven, Connecticut, United States

Christine Y. Bakhoum, MD, MS

• Demkowicz, Patrick Christopher, Yale University School of Medicine, New Haven, Connecticut, United States

Patrick Christopher Demkowicz

• Kumar, Deepika, Yale University School of Medicine, New Haven, Connecticut, United States

Deepika Kumar, MD

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix, MD, FASN

• Moledina, Dennis G., Yale University School of Medicine, New Haven, Connecticut, United States

Dennis G. Moledina, MD, PhD, FASN

• Bakhoum, Mathieu F., Yale University School of Medicine, New Haven, Connecticut, United States

Mathieu F. Bakhoum, MD, PhD

Background

Approximately 60% of patients with systemic lupus erythematosus (SLE) develop nephritis. Histologically-determined disease classification provides clinically actionable information including administration and intensity of immunosuppression, but requires invasive biopsies. We hypothesized DNA methylation patterns from immune cells would be associated with histopathological changes from kidney biopsy in individuals with lupus nephritis.

Methods

We identified 28 participants from the Yale Kidney Biobank with biopsy-confirmed lupus nephritis. A study renal pathologist graded all kidney biopsies according to the NIH Activity and Chronicity Indices. DNA was extracted from blood buffy coat. DNA methylation was analyzed using Illumina MethylationEPIC V2.0, surveying > 935,000 CpG loci. β-values (percent methylation) were derived using the R Sesame package. We utilized the Bioconductor limma package to determine differentially methylated loci by overall indices, as well as by each component of disease activity and chronicity. Benjamini-Hochberg method was used for false discovery rate correction.

Results

The cohort was comprised of participants with the following: class I (n=1), class II (n=3), class III (n=5), class III + V (n=3), class IV (n=4), class IV+V (n=1), class V (n=9), and class VI (n=2). The median activity index was 3 (IQR 1, 7). The median chronicity index was 3 (IQR 2, 6.25). In unadjusted analyses, we identified differentially methylated loci (q < 0.05) by scores including: fibrinoid necrosis, cellular/fibrocellular crescents, global glomerulosclerosis, fibrous crescents, and total chronicity index (Table). After adjustment for age, BMI, sex, and eGFR, loci remained significantly associated with fibrinoid necrosis, cellular/fibrocellular crescents and fibrous crescents.

Conclusion

DNA methylation patterns from immune cells correlate with important histopathologic findings, particularly crescent formation, from kidney biopsy in patients with SLE nephritis.

Funding

• NIDDK Support