Evidence map›Paper›PMID 32448385›Full record

ArticleArthritis research & therapy2020

Cartilage-binding antibodies initiate joint inflammation and promote chronic erosive arthritis.

Yanpeng Li, Dongmei Tong, Peibin Liang, Erik Lönnblom, Johan Viljanen, Bingze Xu, Kutty Selva Nandakumar, Rikard Holmdahl

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

15 citing papers in PubMed, 29 citations in OpenAlex.

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  15. [Strong inflammation is essential for expression of articular cartilage-specific citrullinated antigens].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020
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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

8 authors at 3 institutions in 2 countries.

Yanpeng LiSMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Dongmei TongMedical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-17177, Stockholm, Sweden.
Peibin LiangSMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Erik LönnblomMedical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-17177, Stockholm, Sweden.
Johan ViljanenDepartment of Chemistry Biomedical Center, Uppsala University, Box 576, SE-75123, Uppsala, Sweden.
Bingze XuMedical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-17177, Stockholm, Sweden.
Kutty Selva NandakumarSMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Rikard HolmdahlSMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. rikard.holmdahl@ki.se.ORCID 0000-0002-4969-2576
Karolinska Institutet · SESouthern Medical University · CNUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAntibodies binding to cartilage proteins are present in the blood and synovial fluid of early rheumatoid arthritis patients. In order to develop animal models mimicking the human disease, we have characterized the arthritogenic capacity of monoclonal antibodies directed towards different joint proteins in the cartilage.

methodsPurified antibodies specific to unmodified or citrullinated collagen type II (CII), collagen type XI (CXI), and cartilage oligomeric matrix protein (COMP) were produced as culture supernatant, affinity purified, pooled as antibody cocktails (Cab3 and Cab4), and injected intravenously into mice to induce arthritis. An adjuvant (lipopolysaccharide or mannan) was subsequently injected intraperitoneally on either day 5 or day 60 to enhance arthritis. Antibody binding and complement activation on the cartilage surface were analyzed by immunohistochemical methods. Bone erosions and joint deformations were analyzed by histological assessments, enzyme-linked immunosorbent assays, and micro-CT. Luminex was used to detect CII-triple helical epitope-specific antibody responses.

resultsThe new cartilage antibody cocktails induced an earlier and more severe disease than anti-CII antibody cocktail. Many of the mouse strains used developed severe arthritis with 3 antibodies, binding to collagen II, collagen XI, and cartilage oligomeric matrix protein (the Cab3 cocktail). Two new models of arthritis including Cab3-induced LPS-enhanced arthritis (lpsCAIA) and Cab3-induced mannan-enhanced arthritis (mCAIA) were established, causing severe bone erosions and bone loss, as well as epitope spreading of the B cell response. Cab4, with addition of an antibody to citrullinated collagen II, induced arthritis more efficiently in moderately susceptible C57BL/6 J mice.

conclusionsThe new mouse model for RA induced with cartilage antibodies allows studies of chronic development of arthritis and epitope spreading of the autoimmune response and bone erosion.

Indexed as

Arthritis, ExperimentalAnimalsAutoantibodiesCartilageCollagenCollagen Type IIHumansInflammationMiceMice, Inbred C57BLAutoantibodiesCollagenCollagen Type IIAnimal modelsAntibodiesCartilageCollagenRheumatoid arthritis

Identifiers

PMID32448385
PMCPMC7245816
OpenAlexW3026345602

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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.