Evidence map›Paper›PMID 37986917›Full record

ArticlebioRxiv : the preprint server for biology2023

Coordinated immune dysregulation in Juvenile Dermatomyositis revealed by single-cell genomics.

Gabrielle Rabadam, Camilla Wibrand, Emily Flynn, George C Hartoularos, Yang Sun, Chun Jimmie Ye, Susan Kim, Zev Gartner, Marina Sirota, Jessica Neely

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Gabrielle RabadamUC Berkeley-UC San Francisco Graduate Program in Bioengineering, UCSF, San Francisco, California, USA.
Camilla WibrandAarhus University, Aarhus, Denmark.
Emily FlynnCoLabs, UCSF, San Francisco, California, USA.
George C HartoularosGraduate Program in Biological and Medical Informatics, UCSF, San Francisco, California, USA.ORCID 0000-0001-6980-2368
Yang SunDivision of Rheumatology, Department of Medicine, UCSF, San Francisco, California, USA.
Chun Jimmie YeDivision of Rheumatology, Department of Medicine, UCSF, San Francisco, California, USA.ORCID 0000-0001-6560-3783
Susan KimDivision of Pediatric Rheumatology, Department of Pediatrics, UCSF, San Francisco, California, USA.
Zev GartnerDepartment of Pharmaceutical Chemistry, UCSF, San Francisco, California, USA.
Marina SirotaBakar Computational Health Sciences Institute, UCSF, San Francisco, California, USA.
Jessica NeelyDivision of Pediatric Rheumatology, Department of Pediatrics, UCSF, San Francisco, California, USA.
University of California, San Francisco · USCity College of San Francisco · US

Funding

UCSF/UCB Joint Graduate Group in BIoengineeringT32GM008155 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DESAI, TEJAL A. · 1985 to 2020
$12.2M
RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
Integrative Program in Complex Biological System (ipCBS)T32EB009383 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSHALL, WALLACE, WEINER, ORION D · 2009 to 2022
$3.2M
MULTIseq: multiplexing massively parallel single cell transcriptional analysis across time, space, and conditionsR01GM135462 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GARTNER, ZEV JORDAN · 2019 to 2022
$1.3M
Universal Sample Multiplexing for Single Cell AnalysisR33CA247744 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GARTNER, ZEV JORDAN · 2021 to 2023
$1.2M
Harnessing single cell RNA sequencing and integrative bioinformatics to identify precision therapeutics for dermatomyositisK08AR081983 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jessica Neely · 2023 to 2026
$699k
NCI NIH HHS R33 CA247744NIAMS NIH HHS K08 AR081983NIAMS NIH HHS P30 AR070155NIBIB NIH HHS T32 EB009383NIGMS NIH HHS R01 GM135462NIGMS NIH HHS T32 GM008155
6 · The paper itself

Abstract

Juvenile Dermatomyositis (JDM) is one of several childhood-onset autoimmune disorders characterized by a type I interferon response and autoantibodies. Treatment options are limited due to incomplete understanding of how the disease emerges from dysregulated cell states across the immune system. We therefore investigated the blood of JDM patients at different stages of disease activity using single-cell transcriptomics paired with surface protein expression. By immunophenotyping peripheral blood mononuclear cells, we observed skewing of the B cell compartment towards an immature naive state as a hallmark of JDM. Furthermore, we find that these changes in B cells are paralleled by signatures of Th2-mediated inflammation. Additionally, our work identified SIGLEC-1 expression in monocytes as a composite measure of heterogeneous type I interferon activity in disease. We applied network analysis to reveal that hyperactivation of the type I interferon response in all immune populations is coordinated with dysfunctional protein processing and regulation of cell death programming. This analysis separated the ubiquitously expressed type I interferon response into a central hub and revealed previously masked cell states. Together, these findings reveal the coordinated immune dysregulation underpinning JDM and provide novel insight into strategies for restoring balance in immune function.

Identifiers

PMID37986917
PMCPMC10659396
OpenAlexW4388599271

What Socratic holds

Textmetadata
LicenceCC BY-ND
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 Socratic graph.