Evidence map›Paper›PMID 26059223›Full record

ArticleArthritis research & therapy2015

Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens.

Cátia Fernandes-Cerqueira, Elena Ossipova, Sunithi Gunasekera, Monika Hansson, Linda Mathsson, Anca I Catrina, Yngve Sommarin, Lars Klareskog, Karin Lundberg, Johan Rönnelid and 2 more

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.8field-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

21 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review on the o-Aminoaniline Moiety in Peptide and Protein Chemistry.Chembiochem : a European journal of chemical biology · 2025
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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

12 authors at 3 institutions in 2 countries.

Cátia Fernandes-CerqueiraRheumatology Unit, Department Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden. catia.cerqueira@ki.se.
Elena OssipovaRheumatology Unit, Department Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden. elena.ossipova@ki.se.
Sunithi GunasekeraDivision of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Husargatan 3, 751 23, Uppsala, Sweden. sunithi.gunasekera@fkog.uu.se.
Monika HanssonRheumatology Unit, Department Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden. monika.hansson@ki.se.
Linda MathssonDepartment of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjölds v 20, 751 85, Uppsala, Sweden. linda.mathsson@igp.uu.se.
Anca I CatrinaRheumatology Unit, Department Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden. anca.catrina@ki.se.
Yngve SommarinEuro-Diagnostica AB, Lundavägen 151, 202 11, Malmö, Sweden. yngve.sommarin@eurodiagnostica.com.
Lars KlareskogRheumatology Unit, Department Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden. lars.klareskog@ki.se.
Karin LundbergRheumatology Unit, Department Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden. karin.lundberg@ki.se.
Johan RönnelidDepartment of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarskjölds v 20, 751 85, Uppsala, Sweden. johan.ronnelid@igp.uu.se.
Ulf GöranssonDivision of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Husargatan 3, 751 23, Uppsala, Sweden. ulf.goransson@fkog.uu.se.
Per-Johan JakobssonRheumatology Unit, Department Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden. per-johan.jakobsson@ki.se.
Karolinska University Hospital · SEUppsala University · SECytodiagnostics (Canada) · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionWe have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA).

methodsThe autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC® system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP)2 using the CCPlus® ELISA kit.

resultsTwo peptides derived from the fibrinogen α chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen β chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65%, 15%, 35%, and 53% of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5% (Cit573), 6% (Cit591), 8% (Cit72), and 4% (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84% and 63% respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency.

conclusionsHere we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.

Indexed as

Arthritis, RheumatoidAutoantibodiesAutoantigensCitrullineEnzyme-Linked Immunosorbent AssayEpitopesFibrinogenHumansPeptidesPeptides, CyclicProtein Array AnalysisAutoantibodiesAutoantigensCitrullinecyclic citrullinated peptideEpitopesFibrinogenPeptidesPeptides, Cyclic

Identifiers

PMID26059223
PMCPMC4484629
OpenAlexW1869695152

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LicenceCC BY
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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.