Evidence map›Paper›PMID 42680511›Full record

ArticleLupus science & medicine2026

Genetic and epigenetic determinants of relapse risk in lupus nephritis.

Elisabeth Skoglund, Oliver Skoglund, Holme Vestin, Nina Oparina, Ahmed Sayadi, Francesca Faustini, Elisabet Svenungsson, Lars Ronnblom, Maria K Svensson, Juliana Imgenberg-Kreuz and 3 more

Abstract read
In one paragraph

Article in Lupus science & medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Elisabeth SkoglundDepartment of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden elisabeth.skoglund@medsci.uu.se.ORCID http://orcid.org/0000-0003-4243-9575
Oliver SkoglundDivision of Inflammation and Infection/Rheumatology, Department of Biomedical and Clinical Sciences, Linkoping University, Linköping, Östergötland County, Sweden.
Holme VestinDepartment of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0009-0005-6622-8897
Nina OparinaDepartment of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-3179-1258
Ahmed SayadiDepartment of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.
Francesca FaustiniRheumatology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-6753-7107
Elisabet SvenungssonRheumatology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-3396-3244
Lars RonnblomDepartment of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-9403-6503
Maria K SvenssonDept. of Medical Sciences, Renal Medicine, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-7545-5585
Juliana Imgenberg-KreuzDepartment of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-7230-8990
Iva GunnarssonRheumatology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Christopher SjöwallDivision of Inflammation and Infection/Rheumatology, Department of Biomedical and Clinical Sciences, Linkoping University, Linköping, Östergötland County, Sweden.ORCID http://orcid.org/0000-0003-0900-2048
Dag LeonardDepartment of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-6275-7282

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveLupus nephritis (LN) is a potentially severe manifestation of SLE, often resulting in permanent kidney damage. We investigated whether polygenic and/or epigenetic risk is associated with time to LN relapse and whether this association differs by initial therapy.

methodsCaucasian patients with biopsy-verified LN between 1974 and 2022 (n=149) were genotyped using the Illumina Global Screening Array, and DNA methylation was assessed with the Illumina HumanMethylation450k BeadChip. A weighted Polygenic Risk Score (PRS) based on 55 non-Human leukocyte antigen (HLA) SLE risk gene variants and a Methylation Risk Score (MRS) based on the 17 most differentially methylated cytosine-phosphate-guanine sites identified in SLE-control comparison were calculated. Time to LN relapse was analysed using Cox proportional hazards models, adjusted for centre, sex and year of the first LN.

resultsNeither PRS nor MRS was associated with time to LN relapse in the overall cohort, irrespective of treatment (PRS: HR=1.00 (0.77-1.30); p=0.99; MRS: HR=1.01 (1.00-1.02); p=0.21). No associations were observed among cyclophosphamide (CYC)-treated patients (PRS: HR=0.81 (0.55-1.20); p=0.29; MRS: HR=1.00 (0.99-1.02); p=0.89). In non-CYC-treated patients, PRS showed a non-significant trend towards shorter time to LN relapse (HR=1.26 (0.88-1.81); p=0.21), with a similar trend for MRS (HR=1.02 (1.00-1.03); p=0.066). Adding MRS to the PRS model improved performance in this subgroup (likelihood ratio test, p=0.028), with significant associations for MRS (PRS: HR=1.56 (0.97-2.50); p=0.066; MRS: HR=1.02 (1.00-1.04); p=0.037).

conclusionsGenetic and epigenetic susceptibility appears to influence LN relapse risk in a treatment-dependent manner. The absence of an association among patients receiving CYC suggests that initial treatment with CYC may attenuate the impact of genetic and epigenetic predisposition on relapse. These findings support the potential of genetic and epigenetic profiling at LN diagnosis to improve relapse risk stratification and individualise selection of treatment.

Indexed as

Epigenesis, GeneticLupus NephritisAdultCyclophosphamideDNA MethylationFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansImmunosuppressive AgentsMaleMiddle AgedProportional Hazards ModelsRecurrenceRisk FactorsCyclophosphamideImmunosuppressive AgentsLupus Erythematosus, SystemicLupus NephritisPolymorphism, Genetic

Identifiers

PMID42680511
PMCPMC13536080

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