Evidence map›Paper›PMID 30111803›Full record

ReviewNature reviews. Rheumatology2018

Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction.

V Michael Holers, M Kristen Demoruelle, Kristine A Kuhn, Jane H Buckner, William H Robinson, Yuko Okamoto, Jill M Norris, Kevin D Deane

Registry-linked trialOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Nature reviews. Rheumatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05790356 (Fecal Microbial Transplantation for Rheumatoid Arthritis Trial), which is not on this map. Cited by 234 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
234citing papers in PubMed, 4 pooled it
24.5field-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.

NCT05790356 narecruitingnot on this mapstarted 2023, after this paper: background citation

Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

TypeinterventionalSponsorLondon Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sRan2023 to 2026Enrolled30ConditionsArthritis, Arthritis, Rheumatoid, Fecal Microbiota TransplantationArmsFecal Microbial transplant, Placebo capsules
3 · Its place in the literature

Who cites it

234 citing papers in PubMed, 4 syntheses or guidelines pooled it, 396 citations in OpenAlex.

  1. Pooled it
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  10. Lung disease in rheumatoid arthritis.Nature reviews. Rheumatology · 2026
    Review
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174 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

8 authors at 4 institutions in 1 country.

V Michael HolersDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, USA. michael.holers@ucdenver.edu.
M Kristen DemoruelleDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, USA.
Kristine A KuhnDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, USA.
Jane H BucknerBenaroya Research Institute, Seattle, WA, USA.
William H RobinsonDivision of Immunology and Rheumatology, Stanford University, Stanford, CA, USA.
Yuko OkamotoDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, USA.
Jill M NorrisDepartment of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
Kevin D DeaneDivision of Rheumatology, University of Colorado-Denver, Aurora, CO, USA.
University of Colorado Denver · USBenaroya Research InstituteColorado School of Public Health · USStanford University · US

Funding

Virginia Mason/UCHSC Autoimmune Prevention CenterU19AI050864 · NIAID · UNIVERSITY OF COLORADO DENVER · PI EISENBARTH, GEORGE S · 2001 to 2011
$29.2M
Prevention Center U01: Early Targets for Antigen-Specific Tolerance Induction in Preclinical Rheumatoid ArthritisU01AI101981 · NIAID · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2012 to 2021
$6.2M
Research Training in Rheumatology INCLUDE Down Syndrome SupplementT32AR007534 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI Kristine A. Kuhn · 1986 to 2026
$6.1M
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
RA-Related Autoantibodies in Healthy FDR of RA PatientsR01AR051394 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI NORRIS, JILL M · 2005 to 2011
$3.0M
Development of colonic intraepithelial lymphocytes and their role in epithelial and immune functionK08DK107905 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI KUHN, KRISTINE A. · 2016 to 2020
$716k
Colorado Autoimmunity Center of ExcellenceUM1AI110503 · NIAID · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2014 to 2018
$543k
NIAID NIH HHS U01 AI101981NIAID NIH HHS U19 AI050864NIAID NIH HHS UM1 AI110503NIAMS NIH HHS R01 AR051394NIAMS NIH HHS T32 AR007534NIAMS NIH HHS UH2 AR067681NIDDK NIH HHS K08 DK107905
6 · The paper itself

Abstract

Individuals at high risk of developing seropositive rheumatoid arthritis (RA) can be identified for translational research and disease prevention studies through the presence of highly informative and predictive patterns of RA-related autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in the serum. In serologically positive individuals without arthritis, designated ACPA positive at risk, the presence of mucosal inflammatory processes associated with the presence of local ACPA production has been demonstrated. In other at-risk populations, local RA-related autoantibody production is present even in the absence of serum autoantibodies. Additionally, a proportion of at-risk individuals exhibit local mucosal ACPA production in the lung, as well as radiographic small-airway disease, sputum hypercellularity and increased neutrophil extracellular trap formation. Other mucosal sites in at-risk individuals also exhibit autoantibody production, inflammation and/or evidence of dysbiosis. As the proportion of individuals who exhibit such localized inflammation-associated ACPA production is substantially higher than the likelihood of an individual developing future RA, this finding raises the hypothesis that mucosal ACPAs have biologically relevant protective roles. Identifying the mechanisms that drive both the generation and loss of externally focused mucosal ACPA production and promote systemic autoantibody expression and ultimately arthritis development should provide insights into new therapeutic approaches to prevent RA.

Indexed as

Anti-Citrullinated Protein AntibodiesArthritis, RheumatoidEarly DiagnosisHumansMucous MembraneOrgan SpecificityAnti-Citrullinated Protein Antibodies

Identifiers

PMID30111803
PMCPMC6704378
OpenAlexW2886363262

What OpenQuestion holds

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Registered trials

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.