Evidence map›Paper›PMID 32224441›Full record

ArticleInternational immunopharmacology2020

Immunogenic and inflammatory responses to citrullinated proteins are enhanced following modification with malondialdehyde-acetaldehyde adducts.

Geoffrey M Thiele, Michael J Duryee, Carlos D Hunter, Bryant R England, Benjamin S Fletcher, Eric C Daubach, Taylor P Pospisil, Lynell W Klassen, Ted R Mikuls

Open access · greenAbstract read
In one paragraph

Article in International immunopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 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 2 institutions in 1 country.

Geoffrey M ThieleDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA. Electronic address: gthiele@unmc.edu.
Michael J DuryeeDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
Carlos D HunterDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA.
Bryant R EnglandDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
Benjamin S FletcherDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA.
Eric C DaubachDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA.
Taylor P PospisilDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA.
Lynell W KlassenDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA.
Ted R MikulsDepartment of Internal Medicine, Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE, USA; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
University of Nebraska Medical Center · USVA Nebraska Western Iowa Health Care System · US

Funding

Tracking and Evaluation CoreU54GM115458 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOLSTEIN, SARAH A · 2016 to 2025
$42.8M
Pathogenic Role of Malondialdehyde-Acetaldehyde Adducts in Rheumatoid ArthritisI01BX004660 · VA · OMAHA VA MEDICAL CENTER · PI MIKULS, TED RICHARD · 2020 to 2023
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BLRD VA I01 BX004660BLRD VA IS1 BX004790NIGMS NIH HHS U54 GM115458
6 · The paper itself

Abstract

BACKGROUND/

objectiveMalondialdehyde-acetaldehyde adducts (MAA) act as potent immune adjuvants and co-localize with citrullinated antigens in tissues effected by rheumatoid arthritis (RA). We sought to examine the role of MAA-adducts in promoting RA-related autoimmunity and inflammation.

methodsDBA/J1 mice were immunized with human serum albumin (HSA), HSA-MAA, citrullinated HSA (HSA-Cit), or HSA-MAA-Cit with subsequent measurement of serum anti-citrullinated protein antibody (ACPA) and anti-Cit T cell responses. Cellular binding of the same antigens was examined using THP-1 monocytes and Chinese Hamster Ovary (CHO) cells transfected with specific scavenger receptors (SRs: TLR4, SR-B2, SREC-1). The effects of these antigens on THP-1 activation were then examined by quantifying plate adherence, pro-inflammatory (TNFα, IL-1β, IL-10) cytokine release, and SR (CD14, SR-B2)/co-stimulatory molecule (CD80, HLA-DR) expression. Comparisons were completed using one-way ANOVA with Tukey's post-hoc test.

resultsMice immunized with co-modified HSA produced significantly higher ACPA concentrations than all other groups whereas T cell responses to citrullinated proteins were highest following immunization with HSA-MAA. Both transfected CHO and THP-1 cells demonstrated significantly higher binding of HSA-MAA-Cit vs. HSA or HSA-Cit. THP-1 cells exposed to HSA-MAA-Cit expressed significantly higher concentrations of TNFα, IL-1β, and IL-10 vs. all other groups. Furthermore, THP-1 cells demonstrated significantly increased plate adherence and higher expression of CD14, SR-B2, and HLA-DR following incubation with HSA-MAA-Cit vs. HSA or HSA-Cit.

conclusionThese studies demonstrate that MAA-adduction of citrullinated antigen greatly enhances immune and cellular responses, potentially acting as a key co-factor in RA pathogenesis.

Indexed as

AcetaldehydeAdjuvants, ImmunologicAnimalsAnti-Citrullinated Protein AntibodiesArthritis, RheumatoidCHO CellsCitrullinationCricetulusCytokinesHumansImmunogenicity, VaccineInflammationMaleMalondialdehydeMice, Inbred DBAMonocytesAcetaldehydeAdjuvants, ImmunologicAnti-Citrullinated Protein AntibodiesCytokinesMalondialdehydeReceptors, ScavengerSerum Albumin, HumanAnti-citrullinated protein antibody (ACPA)AutoantibodyCitrullinationMalondialdehyde-acetaldehydeRheumatoid arthritis

Identifiers

PMID32224441
PMCPMC7250734
OpenAlexW3013071480

What OpenQuestion holds

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Registered trials

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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.