Evidence map›Paper›PMID 30152202›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2019

Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell-Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis.

Johanna Steen, Björn Forsström, Peter Sahlström, Victoria Odowd, Lena Israelsson, Akilan Krishnamurthy, Sara Badreh, Linda Mathsson Alm, Joanne Compson, Daniel Ramsköld and 13 more

Open access · hybridAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
14.0field-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.

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

74 citing papers in PubMed, 135 citations in OpenAlex.

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  3. Nonclinical safety assessment of SBT777101, a CAR-engineered regulatory T cell therapy for autoimmune diseases.Toxicological sciences : an official journal of the Society of Toxicology · 2026
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 8 institutions in 5 countries.

Johanna SteenKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Björn ForsströmKTH Royal Institute of Technology, Stockholm, Sweden.
Peter SahlströmKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, and Charité Univeristätsmedizin, Berlin, Germany.
Victoria OdowdUCB Pharma, Slough, UK.
Lena IsraelssonKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Akilan KrishnamurthyKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Sara BadrehKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Linda Mathsson AlmThermo Fisher Scientific and Uppsala University, Uppsala, Sweden.
Joanne CompsonUCB Pharma, Slough, UK.
Daniel RamsköldKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Welcome NdlovuUCB Pharma, Slough, UK.
Stephen RapeckiUCB Pharma, Slough, UK.
Monika HanssonKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Philip J TitcombeKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, and University of Minnesota Medical School, Minneapolis.
Holger BangOrgentec Diagnostika, Mainz, Germany.
Daniel L MuellerUniversity of Minnesota Medical School, Minneapolis.
Anca I CatrinaKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Caroline GrönwallKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.ORCID 0000-0002-9111-5537
Karl SkrinerCharité Univeristätsmedizin, Berlin, Germany.
Peter NilssonKTH Royal Institute of Technology, Stockholm, Sweden.
Daniel LightwoodUCB Pharma, Slough, UK.
Lars KlareskogKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Vivianne MalmströmKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.ORCID 0000-0001-9251-8082
Karolinska University Hospital · SEUCB Pharma (United Kingdom) · GBKTH Royal Institute of Technology · SECharité - Universitätsmedizin Berlin · DEUnitika (Japan) · JPUniversity of Minnesota · USUniversity of Minnesota Medical Center · USUppsala University · SE

Funding

BTCure program 115142-2European Research Council 250167King Gustaf V's 80-year FoundationKnut and Alice Wallenberg FoundationSwedish Association Against RheumatismSwedish Medical Research Council
6 · The paper itself

Abstract

objectiveAntibodies against posttranslationally modified proteins are a hallmark of rheumatoid arthritis (RA), but the emergence and pathogenicity of these autoantibodies are still incompletely understood. The aim of this study was to analyze the antigen specificities and mutation patterns of monoclonal antibodies (mAb) derived from RA synovial plasma cells and address the question of antigen cross-reactivity.

methodsIgG-secreting cells were isolated from RA synovial fluid, and the variable regions of the immunoglobulins were sequenced (n = 182) and expressed in full-length mAb (n = 93) and also as germline-reverted versions. The patterns of reactivity with 53,019 citrullinated peptides and 49,211 carbamylated peptides and the potential of the mAb to promote osteoclastogenesis were investigated.

resultsFour unrelated anti-citrullinated protein autoantibodies (ACPAs), of which one was clonally expanded, were identified and found to be highly somatically mutated in the synovial fluid of a patient with RA. The ACPAs recognized >3,000 unique peptides modified by either citrullination or carbamylation. This highly multireactive autoantibody feature was replicated for Ig sequences derived from B cells from the peripheral blood of other RA patients. The plasma cell-derived mAb were found to target distinct amino acid motifs and partially overlapping protein targets. They also conveyed different effector functions as revealed in an osteoclast activation assay.

conclusionThese findings suggest that the high level of cross-reactivity among RA autoreactive B cells is the result of different antigen encounters, possibly at different sites and at different time points. This is consistent with the notion that RA is initiated in one context, such as in the mucosal organs, and thereafter targets other sites, such as the joints.

Indexed as

Amino Acid MotifsAntibodies, MonoclonalAnti-Citrullinated Protein AntibodiesArthritis, RheumatoidAutoantibodiesAutoantigensFemaleHumansImmunoglobulin GMaleMiddle AgedPlasma CellsProtein CarbamylationProtein Processing, Post-TranslationalSynovial FluidAntibodies, MonoclonalAnti-Citrullinated Protein AntibodiesAutoantibodiesAutoantigensImmunoglobulin G

Identifiers

PMID30152202
PMCPMC6563427
OpenAlexW2889362907

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.