Lupus & antiphospholipid syndrome
Genetic and epigenetic determinants of relapse risk in lupus nephritis
Authors' conclusion
Genetic and epigenetic susceptibility appears to influence LN relapse risk in a treatment-dependent manner.
Study context
- Population
- Caucasian patients with biopsy-verified lupus nephritis (LN) between 1974 and 2022
- Participants
- 149 patients
- Exposure
- Polygenic Risk Score and Methylation Risk Score vs time to LN relapse, by initial therapy (CYC vs non-CYC)
- Outcome
- Time to LN relapse
Methodological detailsCox proportional hazards models adjusted for centre, sex and year of first LN, genotyping and DNA methylation profiling
- Cox proportional hazards models adjusted for centre, sex and year of first LN
- Genotyping and DNA methylation profiling
Main finding
As reported in the abstract
Time to LN relapse, overall cohort
Hazard ratio (CI)P value
PRS
1.00(0.77–1.30)
P = 0.99MRS
1.01(1.00–1.02)
P = 0.21Observational data: associations, not effects.
Further findings
Time to LN relapse, CYC-treated (subgroup)
| HR (CI) | P value | ||
|---|---|---|---|
| PRS | 0.81 (0.55–1.20) | P = 0.29 | |
| MRS | 1.00 (0.99–1.02) | P = 0.89 | |
| 0.512Hazard ratio (log scale) |
Time to LN relapse, non-CYC-treated (subgroup)
| HR (CI) | P value | ||
|---|---|---|---|
| PRSNon-significant trend towards shorter time to relapse | 1.26 (0.88–1.81) | P = 0.21 | |
| MRS | 1.02 (1.00–1.03) | P = 0.066 | |
| 0.512Hazard ratio (log scale) |
Time to LN relapse, non-CYC-treated, combined Polygenic Risk Score (PRS) + Methylation Risk Score (MRS) model (subgroup)
| HR (CI) | P value | ||
|---|---|---|---|
| PRS | 1.56 (0.97–2.50) | P = 0.066 | |
| MRS | 1.02 (1.00–1.04) | P = 0.037 | |
| 0.512Hazard ratio (log scale) |
- Time to LN relapse, non-CYC-treated, combined PRS + MRS model (subgroup) — Adding MRS to PRS model improved performance (likelihood ratio test)
- p=0.028
Original publication
Genetic and epigenetic determinants of relapse risk in lupus nephritis. Lupus Sci Med. Published 1 September 2026. doi:10.
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