Evidence map›Paper›PMID 40368437›Full record

ArticleLupus science & medicine2025

Validation of eight endotypes of lupus based on whole-blood RNA profiles.

Erika Hubbard, Prathyusha Bachali, Amrie C Grammer, Peter E Lipsky

3 registry-linked trialsAbstract readValidation Study
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

NCT03180021 completednot on this map

Dynamic Imaging of Variation in Lupus Nephritis

TypeobservationalSponsorRILITE FoundationRan2018 to 2020Enrolled21ConditionsLupus NephritisArmsMRI
NCT03626311 nacompletednot on this map

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)

TypeinterventionalSponsorAker BioMarine Human Ingredients ASRan2018 to 2021Enrolled76ConditionsSystemic Lupus Erythematosus (SLE)ArmsAKBM-3031, Placebo
NCT05845593 unknown statusnot on this map

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)

TypeobservationalSponsorAmpel BioSolutions, LLCRan2023 to 2025Enrolled200ConditionsLupus Erythematosus, SystemicArmsDecision Support Test
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
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

4 authors.

Erika HubbardBioinformatics and Biostatistics, The George Washington University, Washington, District of Columbia, USA ehubbard28@gwu.edu.ORCID 0000-0002-7972-2879
Prathyusha BachaliAMPEL BioSolutions LLC, Charlottesville, Virginia, USA.
Amrie C GrammerAMPEL BioSolutions LLC, Charlottesville, Virginia, USA.
Peter E LipskyAMPEL BioSolutions LLC, Charlottesville, Virginia, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Lupus Erythematosus, SystemicRNAAdultAlgorithmsAutoantibodiesBiomarkersFemaleGene Expression ProfilingHumansLupus NephritisMaleMiddle AgedMulticenter Studies as TopicObservational Studies as TopicProspective StudiesRandomized Controlled Trials as TopicAutoantibodiesBiomarkersRNAAutoimmunityInflammationLupus Erythematosus, SystemicLupus Nephritis

Identifiers

PMID40368437
PMCPMC12083367

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.