ArticleLupus science & medicine2025
Validation of eight endotypes of lupus based on whole-blood RNA profiles.
Article in Lupus science & medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 5 papers.
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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.
Dynamic Imaging of Variation in Lupus Nephritis
A Double-Blind, Placebo-Controlled Randomized, Multicenter Study to Assess Changes in Omega-3 Index in Erythrocytes and Health Benefit After 24 Weeks of Daily Consumption of AKBM-3031 (Omega-3 Phospholipids From Krill), Followed by a 24 Week Open-Label Extension, in Patients With Systemic Lupus Erythematosus (SLE)
An Open Label Multicenter Study to Assess the Relationship Between Data Obtained With the LuGENE® Multiparameter Transcriptomics Blood Test and Clinical and Standard Laboratory Features of Patients With Systemic Lupus Erythematosus (SLE)
Who cites it
5 citing papers in PubMed.
- Article
- M5542, a bifunctional fusion protein targeting CD80, CD86, and OX40L that modulates excessive T-cell activity: a preclinical proof-of-concept study.Frontiers in immunology · 2026Article
- Pain in systemic lupus erythematosus: emerging insights and paradigms.Nature reviews. Rheumatology · 2025Review
- Dialogue: Validation of eight endotypes of lupus based on whole-blood RNA profiles.Lupus science & medicine · 2025Article
- Multi-omics-driven biomarker discovery in autoimmune diseases: a comprehensive review.Frontiers in immunology · 2025Review
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe previously described a classification system of persons with SLE based on whole blood RNA profiles and a random forest (RF) algorithm to predict individual patient endotypes. Here, we apply this algorithm prospectively in an independent set of patients to validate its use as a staging biomarker.
methodsWhole blood from 101 patients participating in three clinical trials (NCT03626311, NCT03180021 and NCT05845593) meeting American College of Rheumatology (ACR) or Systemic Lupus Collaborating Clinics (SLICC) criteria for SLE classification was obtained at baseline, and RNA isolated and sequenced. Gene expression values were used as input to gene set variation analysis (GSVA), and the RF algorithm was applied using GSVA enrichment scores of 32 informative gene sets as input. Composite scores summarising gene expression perturbations were assigned to each patient using a ridge logistic regression algorithm.
resultsPatients with SLE were subset into eight endotypes identified by the algorithm. Patterns of gene enrichment in the identified endotypes mirrored those found in the previously reported endotypes. Differences in clinical characteristics, including serum complement levels, autoantibody positivity and the presence of nephritis, were observed between patients in various endotypes. Patients with active, concurrent nephritis were disproportionately assigned to the more molecularly perturbed endotypes. Composite scores were significantly, but modestly, inversely correlated with complement but not SLE Disease Activity Index (SLEDAI) or anti-double-stranded DNA antibody (anti-dsDNA) titre.
conclusionsThe identification of eight molecular endotypes of lupus based on whole blood gene expression was validated in an independent data set of diverse patients. Endotyping patients with SLE based on transcriptional profiles can provide important status (presence of nephritis) information and provide novel molecular insights in support of personalised management.
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Registered trials
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