Evidence map›Paper›PMID 34334364›Full record

ArticleThe Journal of rheumatology2022

Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope Protein in Patients With Rheumatoid Arthritis.

Xiaoxing Wang, Amanda Hefton, Kathryn Ni, Kennedy C Ukadike, Michael A Bowen, Mary Eckert, Anne Stevens, Christian Lood, Tomas Mustelin

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of rheumatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

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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

9 authors at 4 institutions in 1 country.

Xiaoxing WangX. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Amanda HeftonX. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Kathryn NiX. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Kennedy C UkadikeX. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.
Michael A BowenM.A. Bowen, PhD, Product and Process Development, Allogene Therapeutics, San Francisco, California.
Mary EckertM. Eckert, BS, Seattle Children's Research Institute, Seattle, Washington.
Anne StevensA. Stevens, MD, Professor, Seattle Children's Research Institute, Seattle, Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington, and Janssen Research & Development, LLC, Wayne, Pennsylvania, USA.
Christian LoodX. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.ORCID 0000-0002-6171-1952
Tomas MustelinX. Wang, PhD, A. Hefton, K. Ni, BS, K.C. Ukadike, MD, Acting Instructor, C. Lood, PhD, Associate Professor, T. Mustelin, MD, PhD, Professor, Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington; tomas2@uw.edu.ORCID 0000-0001-5912-8840
University of Washington · USAllogene Therapeutics (United States) · USSeattle Children's Hospital · USSeattle Children's Hospital · US

Funding

RESEARCH TRAINING IN RHEUMATOLOGYT32AR007108 · NIAMS · UNIVERSITY OF WASHINGTON · PI Shaun Jackson, Tomas M Mustelin · 1986 to 2026
$6.6M
Role of protein citrullination in rheumatoid arthritisR01AR074939 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2020 to 2024
$1.9M
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
HERV-K immunity, a trigger of citrullination in rheumatoid arthritis?R21AR077266 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2021 to 2022
$425k
NIAMS NIH HHS R01 AR074939NIAMS NIH HHS R21 AR075134NIAMS NIH HHS R21 AR077266NIAMS NIH HHS T32 AR007108
6 · The paper itself

Abstract

objectiveAutoantibodies against proteins encoded by human endogenous retrovirus K (HERV-K) have been reported in patients with rheumatoid arthritis (RA), but their relevance, if any, has remained unresolved. We revisited this question and tested if such autoantibodies may react with citrullinated epitopes on the envelope (Env) protein of HERV-K.

methodsImmunoblotting and ELISAs were conducted with unmodified Env protein and with Env citrullinated by protein arginine deiminase 4 (PAD4). Sera from 100 patients with RA, plasma from 32 patients with juvenile idiopathic arthritis (JIA), and healthy adult and pediatric controls were included. Antibody reactivity was evaluated for correlations with clinical and laboratory variables of the patients.

resultsWe replicated and expanded upon published data suggesting that patients with RA or JIA have autoantibodies against HERV-K Env, some with high titers. Anti-HERV-K antibodies correlated with cigarette smoking and with circulating myeloperoxidase-DNA complexes indicative of nonapoptotic neutrophil cell death. Further, most of the patients with RA, but not those with JIA, had autoantibodies that reacted more strongly with Env that was citrullinated by PAD4. These anticitrullinated Env autoantibodies correlated with seropositivity and tended to be higher in patients with erosive disease.

conclusionOur data suggest that anti-HERV-K immunity is elevated in RA and JIA and may have a connection with pathogenic protein citrullination in RA.

Indexed as

Arthritis, RheumatoidEndogenous RetrovirusesAutoantibodiesChildGene Products, envHumansProtein-Arginine Deiminase Type 4AutoantibodiesGene Products, envProtein-Arginine Deiminase Type 4citrullinationendogenous retrovirus Kenvelopejuvenile idiopathic arthritisrheumatoid arthritis

Identifiers

PMID34334364
PMCPMC8963793
OpenAlexW3192585186

What OpenQuestion 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 OpenQuestion graph.