Evidence mapPaperPMID 38448779Full record

ArticleNature immunology2024

Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression.

Kaitlin R Carroll, Mark Mizrachi, Sean Simmons, Bahtiyar Toz, Czeslawa Kowal, Jeffrey Wingard, Nazila Tehrani, Aida Zarfeshani, Nina Kello, Lara El Khoury and 4 more

Open access · greenAbstract read
In one paragraph

Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Kaitlin R Carroll *Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Mark Mizrachi *Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.ORCID http://orcid.org/0000-0003-2067-9914
Sean SimmonsStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Bahtiyar TozInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Czeslawa KowalInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Jeffrey WingardInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Nazila TehraniInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Aida ZarfeshaniInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Nina KelloNorthwell Health, Manhasset, NY, USA.ORCID http://orcid.org/0000-0001-5497-7472
Lara El KhouryNorthwell Health, Manhasset, NY, USA.
Rachel Weissman-TsukamotoInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Joshua Z LevinStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Bruce T VolpeInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Betty DiamondInstitute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY, USA. bdiamond@northwell.edu.ORCID http://orcid.org/0000-0002-3250-3804
Feinstein Institute for Medical Research · USBroad Institute · USNorthwell Health · US

Funding

The Monoclonal Antibody and Reagent CoreP01AI073693 · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2025 to 2025
$2.5M
T32 Training Grant in Translational ImmunologyT32AI155392 · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2025 to 2025
$302k
NIAID NIH HHS P01 AI073693NIAID NIH HHS T32 AI155392
6 · The paper itself

Abstract

Cognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus, present in up to 80% of patients and leading to a diminished quality of life. In the present study, we used a model of lupus-like cognitive impairment that is initiated when antibodies that crossreact with excitatory neuronal receptors penetrate the hippocampus, causing immediate, self-limited, excitotoxic death of hippocampal neurons, which is then followed by a significant loss of dendritic complexity in surviving neurons. This injury creates a maladaptive equilibrium that is sustained in mice for at least 1 year. We identified a feedforward loop of microglial activation and microglia-dependent synapse elimination dependent on neuronal secretion of high mobility group box 1 protein (HMGB1) which binds the receptor for advanced glycation end products (RAGE) and leads to microglial secretion of C1q, upregulation of interleukin-10 with consequent downregulation of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), an inhibitory receptor for C1q. Treatment with a centrally acting angiotensin-converting enzyme inhibitor or with an angiotensin-receptor blocker restored a healthy equilibrium, microglial quiescence and intact spatial memory.

Indexed as

AutoantibodiesHMGB1 ProteinAnimalsComplement C1qMiceNeuroinflammatory DiseasesQuality of LifeReceptor for Advanced Glycation End ProductsReceptors, ImmunologicAger protein, mouseAutoantibodiesComplement C1qHMGB1 ProteinHMGB1 protein, mouseleukocyte-associated immunoglobulin-like receptor 1Receptor for Advanced Glycation End ProductsReceptors, Immunologic

Identifiers

PMID38448779
PMCPMC11141703
OpenAlexW4392518063

What Socratic holds

Textmetadata
LicenceTDM
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.