Evidence map›Paper›PMID 34783463›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2022

Urine Proteomics and Renal Single-Cell Transcriptomics Implicate Interleukin-16 in Lupus Nephritis.

Andrea Fava, Deepak A Rao, Chandra Mohan, Ting Zhang, Avi Rosenberg, Paride Fenaroli, H Michael Belmont, Peter Izmirly, Robert Clancy, Jose Monroy Trujillo and 13 more

Open access · greenAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% of its field
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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Biomarkers of Lupus Nephritis Histopathology: Where Do We Stand?Arthritis & rheumatology (Hoboken, N.J.) · 2026
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  16. Lupus nephritis.Nature reviews. Disease primers · 2025
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6 more citing papers are in PubMed but not listed here.

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

23 authors at 6 institutions in 3 countries.

Andrea FavaJohns Hopkins University, Baltimore, Maryland.ORCID 0000-0001-6738-4836
Deepak A RaoHarvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9672-7746
Chandra MohanUniversity of Houston, Houston, Texas.
Ting ZhangUniversity of Houston, Houston, Texas.ORCID 0000-0002-8616-9733
Avi RosenbergJohns Hopkins University, Baltimore, Maryland.
Paride FenaroliJohns Hopkins University, Baltimore, Maryland, and Parma University Hospital, Parma, Italy.
H Michael BelmontNew York University School of Medicine, New York, New York.
Peter IzmirlyNew York University School of Medicine, New York, New York.ORCID 0000-0001-5445-2182
Robert ClancyNew York University School of Medicine, New York, New York.
Jose Monroy TrujilloJohns Hopkins University, Baltimore, Maryland.
Derek FineJohns Hopkins University, Baltimore, Maryland.
Arnon AraziFeinstein Institutes for Medical Research, Manhasset, New York.
Celine C BerthierUniversity of Michigan, Ann Arbor.
Anne DavidsonNorthwell Health, New York, New York.
Judith A JamesOklahoma Medical Research Foundation, Oklahoma City.ORCID 0000-0002-9574-7355
Betty DiamondFeinstein Institutes for Medical Research, Manhasset, New York.
Nir HacohenBroad Institute, Boston, Massachusetts.
David WofsyUniversity of California, San Francisco.
Soumya RaychaudhuriHarvard Medical School, Boston, Massachusetts, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and The University of Manchester, Manchester, UK.
William ApruzzeseHarvard Medical School, Boston, Massachusetts.
Accelerating Medicines Partnership in Rheumatoid Arthritis and Systemic Lupus Erythematosus Network
Jill BuyonNew York University School of Medicine, New York, New York.
Michelle PetriJohns Hopkins University, Baltimore, Maryland.ORCID 0000-0003-1441-5373
Broad Institute · USFeinstein Institute for Medical Research · USJohns Hopkins University · USNorthwell Health · USUniversity of Michigan · USUniversity of Parma · IT

Funding

Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI TIMOTHY M VANWAGONER · 2013 to 2026
$68.2M
PEARL: Pathway Exploration and Analysis in Renal LupusUH2AR067688 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI DIAMOND, BETTY, WOFSY, DAVID · 2014 to 2020
$9.0M
Oklahoma Rheumatic Disease Research Cores Center (Overall Application)P30AR073750 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES · 2018 to 2026
$8.5M
Tissue Acquisition Research GroupUM2AR067678 · NIAMS · STANFORD UNIVERSITY · PI HOLERS, VERNON MICHAEL, UTZ, PAUL JOSEPH · 2014 to 2020
$8.2M
Multi-Ethnic Translational Research Optimization (METRO) Lupus ConsortiumUH2AR067689 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BUYON, JILL P, PUTTERMAN, CHAIM · 2014 to 2020
$6.3M
Evolving Adaptive and Effector Mechanisms from Pre-RA Through Established DiseaseUH2AR067681 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2014 to 2020
$5.5M
Molecular and Cellular Dissection of Early Rheumatoid ArthritisUH2AR067694 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI BRENNER, MICHAEL B., GREGERSEN, PETER K. · 2014 to 2020
$5.4M
Monitoring Disease in LupusR01AR074096 · NIAMS · UNIVERSITY OF HOUSTON · PI CHANDRA MOHAN · 2019 to 2026
$4.5M
RA-SLE Molecular Deconstruction Leadership CenterUH2AR067677 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2014 to 2020
$4.3M
Hopkins Lupus CohortR01AR069572 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI PETRI, MICHELLE A · 2016 to 2020
$3.4M
Cellular Dynamics at the Synovium-Bone interface in RAUH2AR067690 · NIAMS · UNIVERSITY OF ROCHESTER · PI ANOLIK, JENNIFER HOWITT · 2014 to 2020
$3.0M
Stanford Technology Accelerating Medicines Partnership CenterUH2AR067676 · NIAMS · STANFORD UNIVERSITY · PI ROBINSON, WILLIAM H, UTZ, PAUL JOSEPH · 2014 to 2020
$2.6M
NIAMS NIH HHS P30 AR073750NIAMS NIH HHS R01 AR069572NIAMS NIH HHS R01 AR074096NIAMS NIH HHS UH2 AR067676NIAMS NIH HHS UH2 AR067677NIAMS NIH HHS UH2 AR067679NIAMS NIH HHS UH2 AR067681NIAMS NIH HHS UH2 AR067685NIAMS NIH HHS UH2 AR067688NIAMS NIH HHS UH2 AR067689NIAMS NIH HHS UH2 AR067690NIAMS NIH HHS UH2 AR067691NIAMS NIH HHS UH2 AR067694NIAMS NIH HHS UM2 AR067678NIGMS NIH HHS U54 GM104938
6 · The paper itself

Abstract

objectiveCurrent lupus nephritis (LN) treatments are effective in only 30% of patients, emphasizing the need for novel therapeutic strategies. We undertook this study to develop mechanistic hypotheses and explore novel biomarkers by analyzing the longitudinal urinary proteomic profiles in LN patients undergoing treatment.

methodsWe quantified 1,000 urinary proteins in 30 patients with LN at the time of the diagnostic renal biopsy and after 3, 6, and 12 months. The proteins and molecular pathways detected in the urine proteome were then analyzed with respect to baseline clinical features and longitudinal trajectories. The intrarenal expression of candidate biomarkers was evaluated using single-cell transcriptomics of renal biopsy sections from LN patients.

resultsOur analysis revealed multiple biologic pathways, including chemotaxis, neutrophil activation, platelet degranulation, and extracellular matrix organization, which could be noninvasively quantified and monitored in the urine. We identified 237 urinary biomarkers associated with LN, as compared to controls without systemic lupus erythematosus. Interleukin-16 (IL-16), CD163, and transforming growth factor β mirrored intrarenal nephritis activity. Response to treatment was paralleled by a reduction in urinary IL-16, a CD4 ligand with proinflammatory and chemotactic properties. Single-cell RNA sequencing independently demonstrated that IL16 is the second most expressed cytokine by most infiltrating immune cells in LN kidneys. IL-16-producing cells were found at key sites of kidney injury.

conclusionUrine proteomics may profoundly change the diagnosis and management of LN by noninvasively monitoring active intrarenal biologic pathways. These findings implicate IL-16 in LN pathogenesis, designating it as a potentially treatable target and biomarker.

Indexed as

Biological ProductsLupus NephritisBiomarkersFemaleHumansInterleukin-16KidneyMaleProteomicsSingle-Cell AnalysisTranscriptomeBiological ProductsBiomarkersIl16 protein, humanInterleukin-16

Identifiers

PMID34783463
PMCPMC9050800
OpenAlexW3214542715

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.