Evidence map›Paper›PMID 41314814›Full record

ArticleLupus science & medicine2025

Dysregulated soluble immune mediators and lupus-associated autoantibody specificities inform the development of immune indexes that characterise classified SLE transition and SLE disease activity.

Melissa E Munroe, Kendra Young, Rufei Lu, Joel M Guthridge, Diane L Kamen, Gary S Gilkeson, Michael H Weisman, Mariko L Ishimori, Daniel J Wallace, David R Karp and 5 more

Abstract read
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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

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

1 citing paper in PubMed.

  1. Trial
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

15 authors.

Melissa E MunroeArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA melissa-munroe@omrf.org.ORCID 0000-0002-6933-9745
Kendra YoungDepartment of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
Rufei LuArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Joel M GuthridgeArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Diane L KamenDivision of Rheumatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.ORCID 0000-0002-7698-980X
Gary S GilkesonDivision of Rheumatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.ORCID 0000-0003-4228-3574
Michael H WeismanDivision of Rheumatology, Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Mariko L IshimoriDivision of Rheumatology, Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Daniel J WallaceDivision of Rheumatology, Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
David R KarpDivision of Rheumatic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.ORCID 0000-0002-9005-1690
George C TsokosBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Michael P KeithWalter Reed National Military Medical Center, Bethesda, Maryland, USA.
John B HarleyUS Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
Jill M NorrisDepartment of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
Judith A JamesArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.ORCID 0000-0002-9574-7355

Funding

Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Janis E Campbell · 2013 to 2026
$68.2M
Oklahoma Rheumatic Disease Research Cores Center (Overall Application)P30AR073750 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES · 2018 to 2026
$8.5M
HLA GENE COMPLEMENTATION IN PRIMARY SJOGREN'S AND LUPUSR01AI024717 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KOTTYAN, LEAH CLAIRE, WEIRAUCH, MATTHEW TYSON · 1987 to 2025
$7.8M
Pre-Clinical Studies to Identify SLE Therapeutic TargetsU19AI082714 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI GAFFNEY, PATRICK M · 2009 to 2018
$6.2M
Autoimmune Drivers and Protectors Team Science (ADAPTS)U01AI176244 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES, Jeffrey C Rathmell · 2023 to 2026
$5.1M
Science in a Culture of MentoringP30GM103510 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JAMES, JUDITH A · 2012 to 2016
$3.9M
Oklahoma ACE: Molecular Destruction of Autoimmune Disease to Aid Clinical Trail SuccessUM1AI144292 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES · 2019 to 2026
$3.3M
Understanding early events in lupus autoimmunity to aid preventionU01AI101934 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JAMES, JUDITH A · 2012 to 2016
$2.3M
BLRD VA I01 BX001834BLRD VA I01 BX006254NIAID NIH HHS R01 AI024717NIAID NIH HHS U01 AI101934NIAID NIH HHS U01 AI176244NIAID NIH HHS U19 AI082714NIAID NIH HHS UM1 AI144292NIAMS NIH HHS P30 AR073750NIGMS NIH HHS P30 GM103510NIGMS NIH HHS U54 GM104938
6 · The paper itself

Abstract

objectivesSystemic lupus erythematosus (SLE) is a complex autoimmune disease. Significant morbidity and early mortality necessitate early intervention. This study harnessed SLE-associated immune dysregulation to create a Lupus Classification Risk Index (LCRII) and Lupus Disease Activity Immune Index (LDAII) that identified individuals at risk for SLE classification and disease activity.

methodsThe LCRII was developed from 84 military personnel who developed classified SLE (≥4 American College of Rheumatology criteria) versus matched healthy controls, which was confirmed in 56 lupus blood relatives who developed SLE versus 154 matched unaffected relatives and 77 unrelated controls. The LDAII was informed by SLE patient visits with low (n=132) or active (n=179) disease and 48 matched controls. Data from blood samples assessed for circulating SLE-associated autoantibody specificities and soluble immune mediators informed the LCRII and LDAII. Random forest modelling guided the selection of informative analytes.

resultsAn LCRII informed by 32 or 17 log-transformed/standardised mediators, weighted by their correlation to SLE-associated autoantibodies, differentiated pre-SLE individuals before reaching disease classification (area under the curve (AUC) ≥0.79, p<0.0001; effect size ≥1.1), even before the appearance of clinical criteria (AUC ≥0.74, p<0.0001; effect size ≥0.9). The LCRII-32, LCRII-17 and select mediators, MCP-3/CCL7, TNFRII, stem cell factor (SCF), IL-1α, IP-10/CXCL10 and TGF-β differentiated renal and serositis classification criteria (p<0.05). An LDAII informed by 26 or 13 log-transformed/standardised mediators, weighted by their correlation to SLE-associated autoantibodies or disease activity (hybrid Systemic Lupus Erythematosus Disease Activity Index; hSLEDAI), differentiated SLE patients with low (hSLEDAI <4) or active (hSLEDAI ≥4) disease (AUC >0.6, p ≤

conclusionsWe have conceptualised two immune mediator-informed indexes, the LCRII that predicts SLE from months to years before clinical presentation, and the LDAII that analogously predicts active disease in SLE to distinguish patients who would benefit from early intervention.

Indexed as

AutoantibodiesLupus Erythematosus, SystemicAdultBiomarkersCase-Control StudiesFemaleHumansMaleMiddle AgedMilitary PersonnelSeverity of Illness IndexYoung AdultAutoantibodiesBiomarkersAutoantibodiesAutoimmunityCytokinesInflammationSystemic Lupus Erythematosus

Identifiers

PMID41314814
PMCPMC12666031

What Socratic holds

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LicenceCC BY-NC
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Registered trials

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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 Socratic graph.