Evidence map›Paper›PMID 39800670›Full record

ArticleACR open rheumatology2025

Altered Protein Structures and Neoepitopes in Lupus Neutrophils From Dysregulated Splicing of Messenger RNA.

Rayan Najjar, Xiaoxing Wang, Jose Mario Bello Pineda, Hugh Alessi, Alison Bays, Robert K Bradley, James N Jarvis, Tomas Mustelin

Abstract read
In one paragraph

Article in ACR open rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

8 authors.

Rayan NajjarUniversity of Washington, Seattle.ORCID https://orcid.org/0000-0002-9214-521X
Xiaoxing WangUniversity of Washington, Seattle.
Jose Mario Bello PinedaUniversity of Washington, Seattle.
Hugh AlessiUniversity of Washington, Seattle.
Alison BaysUniversity of Washington, Seattle.ORCID https://orcid.org/0000-0002-7193-6303
Robert K BradleyUniversity of Washington, Seattle, and Fred Hutchinson Cancer Research Center, Seattle, Washington.
James N JarvisUniversity of Washington, Seattle.ORCID https://orcid.org/0000-0002-1878-0717
Tomas MustelinUniversity of Washington, Seattle.ORCID https://orcid.org/0000-0001-5912-8840

Funding

RESEARCH TRAINING IN RHEUMATOLOGYT32AR007108 · NIAMS · UNIVERSITY OF WASHINGTON · PI Shaun Jackson, Tomas M Mustelin · 1986 to 2026
$6.6M
Epigenetic Mechanisms That Drive Genetic Risk in Juvenile ArthritisR01AR078785 · NIAMS · UNIVERSITY OF WASHINGTON · PI JAMES N JARVIS · 2022 to 2026
$3.1M
Upstream drivers of type I interferons in lupusR01AI186337 · NIAID · UNIVERSITY OF WASHINGTON · PI Joanne Michelle Kahlenberg, John LaCava · 2024 to 2026
$2.3M
Role of the L1 retrotransposon in interferon-positive SLER01AR081654 · NIAMS · UNIVERSITY OF WASHINGTON · PI Tomas M Mustelin · 2023 to 2026
$2.1M
Role of protein citrullination in rheumatoid arthritisR01AR074939 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2020 to 2024
$1.9M
Regulation of the tumor suppressor PTENR01CA096949 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MUSTELIN, TOMAS M · 2003 to 2006
$1.4M
The roots of SLE: Can we cure it with a reverse transcriptase inhibitor?R21AR075134 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2019 to 2020
$427k
CSR NIH HHS AI188952CSR NIH HHS AR075134, AR074939, and AR081654 to T.M.NCI NIH HHS R01 CA096949NIAID NIH HHS R01 AI186337NIAMS NIH HHS R01 AR074939NIAMS NIH HHS R01 AR078785NIAMS NIH HHS R01 AR081654NIAMS NIH HHS R21 AR075134NIAMS NIH HHS T32 AR007108NIH HHS AI-186337 and AI-183320 (to Dr Mustelin)
6 · The paper itself

Abstract

objectiveTo test whether messenger RNA (mRNA) splicing is altered in neutrophils from patients with systemic lupus erythematosus (SLE) and can produce neoantigens.

methodsRNA sequencing of neutrophils from patients with SLE (n = 15) and healthy donors (n = 12) were analyzed for mRNA splicing using the RiboSplitter pipeline, an event-focused tool based on SplAdder with subsequent translation and protein domain annotation. RNA sequencing from SARS-CoV2-infected individuals was used as an additional comparator.

resultsNeutrophils from patients with SLE contained 521 statistically significant altered mRNA splicing events compared with healthy donor neutrophils, many of them affecting important immunologic pathways, myeloid function, transcription factors, and proteins involved in mRNA splicing. A subset of splicing events were only present in SLE samples, and some of them occurred at unannotated splice acceptor or donor sites. Two patients were particularly rich in such events. Only a small number of dysregulated splicing events were more pronounced in patients with active disease or with high type I interferons but were not detected in SARS-CoV2-infected individuals, who also had high type I interferons. Besides causing a range of structural changes, 80 mRNA splice variants exclusive to SLE were predicted to translate into novel amino acid sequences. Peptides derived from these novel amino acid sequences were predicted to bind to the individual patients' class I and II major histocompatibility complex molecules with high affinity.

conclusionWe conclude that aberrant mRNA splicing in SLE has the potential to affect both the function of granulocytes and to generate novel autoantigens.

Identifiers

PMID39800670
PMCPMC11725403

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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 OpenQuestion graph.