Abstract: TH-OR005
Cell-Free DNA Fragmentomics in Lupus Nephritis: A Pilot Study
Session Information
- Advances in Renal Pathology and Laboratory Medicine
October 22, 2026 | Location: Room 605, Convention Center
Abstract Time: 05:10 PM - 05:20 PM
Category: Pathology and Lab Medicine
- 1700 Pathology and Lab Medicine
Authors
- Ziri, Malek, Biochemistry Department, Assistance Publique Hôpitaux de Paris, Georges Pompidou European Hospital, Paris Cité University, Paris, France
- Chehrit, Redouane, Department of Nephrology, Assistance Publique Hôpitaux de Paris, Georges Pompidou European Hospital, Paris Cité University, Paris, France
- Pereira, Eva, Centre de Recherche des Cordeliers, INSERM U1138, Paris Cité University, Paris, France
- Karras, Alexandre, Department of Nephrology, Assistance Publique Hôpitaux de Paris, Georges Pompidou European Hospital, Paris Cité University, Paris, France
- Pallet, Nicolas, Biochemistry Department, Assistance Publique Hôpitaux de Paris, Georges Pompidou European Hospital, Paris Cité University, Paris, France
- Garinet, Simon, Biochemistry Department, Assistance Publique Hôpitaux de Paris, Georges Pompidou European Hospital, Paris Cité University, Paris, France
Background
Lupus nephritis is a frequent and severe complication of systemic lupus erythematosus (SLE) for which there is no robust biomarker of activity. Cell free DNA (cfDNA), released in the circulation during apoptosis, is widely used in oncology as a non-invasive biomarker. Fragmentomics is an emerging approach based on low-pass whole genome sequencing (lpWGS) of cfDNA, that enables the identification of fragmentation patterns associated with the tissue or cell of origin. Because SLE is characterized by defective clearance of apoptotic bodies, we aimed to identify a fragmentomic signature associated with lupus activity.
Methods
We compared cfDNA fragmentomic signatures in 18 patients who underwent diagnostic kidney biopsy: 9 patients with active lupus nephritis (class III/IV, NIH activity index > 6, hypocomplementemia) and 9 control patients with diabetic nephropathy. Plasma cfDNA was analyzed by lpWGS. Three fragmentomic signatures were evaluated: (1) the D3DS (DNAse1L3 Deficiency Score), based on 5' tetranucleotide end motif; (2) a fragmentation score based on short to long fragment ratios across 5 Mb genomic windows; and (3) the TSS-CFR (transcription start site central-to-flanking ratio), reflecting coverage patterns around transcription start sites.
Results
All three signatures significantly discriminated patients with lupus nephritis from controls (Wilcoxon p < 0.01 for all scores). D3DS showed the best diagnostic performance, followed by the fragmentation score and TSS-CFR (AUC = 0.963, 0.914 and 0.864, respectively). Combining the three scores slightly improved discrimination (AUC = 0.975). In one patient assessed before and after induction therapy, all scores normalized following remission. Cell of origin analysis of cfDNA in lupus patients demonstrated enrichment for endothelial cells and macrophages.
Conclusion
This pilot study highlights the potential of cfDNA fragmentomics as an innovative biomarker of lupus nephritis activity.
Graphical abstract. Schematic overview of the main fragmentomic analyses performed and key findings.
Funding
- Government Support – Non-U.S.