Evidence map›Paper›PMID 25326381›Full record

ReviewThe Journal of biological chemistry2014

Functional analysis of the anti-adalimumab response using patient-derived monoclonal antibodies.

Pauline A van Schouwenburg, Simone Kruithof, Christian Votsmeier, Karin van Schie, Margreet H Hart, Rob N de Jong, Esther E L van Buren, Marieke van Ham, Lucien Aarden, Gertjan Wolbink and 2 more

Open access · hybridAbstract readReview
In one paragraph

Review in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
5.6field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 71 citations in OpenAlex.

  1. Trial
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  7. Review
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  12. Assessing Immunogenicity of Biologic Drugs in Inflammatory Joint Diseases: Progress Towards Personalized Medicine.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022
    Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Immunogenicity of TNF-Inhibitors.Frontiers in immunology · 2020
    Review
  19. Article
  20. Article
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 3 countries.

Pauline A van SchouwenburgFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Simone KruithofFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Christian VotsmeierGlobal Drug Discovery, Global Biologics, Bayer HealthCare AG, 51061 Cologne, Germany, and.
Karin van SchieFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Margreet H HartFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Rob N de JongGenmab B.V., 3584 BV Utrecht, The Netherlands.
Esther E L van BurenGenmab B.V., 3584 BV Utrecht, The Netherlands.
Marieke van HamFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Lucien AardenFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Gertjan WolbinkFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands, the Jan van Breemen Research Institute/Reade, 1056 AB Amsterdam, The Netherlands.
Diana WoutersFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Theo RispensFrom the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands, t.rispens@sanquin.nl.
Sanquin · NLGenmab (Netherlands) · NLBayer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The production of antibodies to adalimumab in autoimmune patients treated with adalimumab is shown to diminish treatment efficacy. We previously showed that these antibodies are almost exclusively neutralizing, indicating a restricted response. Here, we investigated the characteristics of a panel of patient-derived monoclonal antibodies for binding to adalimumab. Single B-cells were isolated from two patients, cultured, and screened for adalimumab specificity. Analysis of variable region sequences of 16 clones suggests that the immune response against adalimumab is broad, involving multiple B-cell clones each using different combinations of V(D)J segments. A strong bias for replacement mutations in the complementarity determining regions was found, indicating an antigen-driven response. We recombinantly expressed 11 different monoclonal antibodies and investigated their affinity and specificity. All clones except one are of high affinity (Kd between 0.6 and 233 pm) and compete with TNF as well as each other for binding to adalimumab. However, binding to a panel of single-point mutants of adalimumab indicates markedly different fine specificities that also result in a differential tendency of each clone to form dimeric and multimeric immune complexes. We conclude that although all anti-adalimumab antibodies compete for binding to TNF, the response is clonally diverse and involves multiple epitopes on adalimumab. These results are important for understanding the relationship between self and non-self or idiotypic determinants on therapeutic antibodies and their potential immunogenicity.

Indexed as

AdalimumabAmino Acid SequenceAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibody SpecificityHEK293 CellsHumansImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsImmunoglobulin Variable RegionMolecular Sequence DataPoint MutationAdalimumabAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsImmunoglobulin Variable RegionAdalimumabAntibody EngineeringAutoimmune DiseaseBiotechnologyHumoral ResponseImmunogenicityMonoclonal AntibodyTumor Necrosis Factor (TNF)

Identifiers

PMID25326381
PMCPMC4263856
OpenAlexW2013754528

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.