Evidence map›Paper›PMID 27213814›Full record

ArticleMolecular immunology2016

VNAR single-domain antibodies specific for BAFF inhibit B cell development by molecular mimicry.

Julien Häsler, Martin F Flajnik, Gareth Williams, Frank S Walsh, J Lynn Rutkowski

Open access · greenAbstract read
In one paragraph

Article in Molecular immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. VNAR development through antigen immunization of Japanese topeshark (Frontiers in bioengineering and biotechnology · 2023
    Article
  6. A novel PD-L1-targeted shark VMolecular therapy oncolytics · 2022
    Article
  7. Article
  8. Review
  9. Review
  10. Bamboo Shark as a Small Animal Model for Single Domain Antibody Production.Frontiers in bioengineering and biotechnology · 2021
    Article
  11. Review
  12. Review
  13. Single domain antibodies for the knockdown of cytosolic and nuclear proteins.Protein science : a publication of the Protein Society · 2017
    Review
  14. 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

5 authors at 4 institutions in 2 countries.

Julien HäslerOssianix, Ltd, Stevenage Bioscience Catalyst, Gunnels Wood Rd, Stevenage, Hertfordshire SG12FX, UK.
Martin F FlajnikDepartment of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD 21201, USA.
Gareth WilliamsWolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK.
Frank S WalshOssianix, Ltd, Stevenage Bioscience Catalyst, Gunnels Wood Rd, Stevenage, Hertfordshire SG12FX, UK; Ossianix, Inc, University City Science Center, 3711 Market St, Philadelphia, PA 19014, USA.
J Lynn RutkowskiOssianix, Ltd, Stevenage Bioscience Catalyst, Gunnels Wood Rd, Stevenage, Hertfordshire SG12FX, UK; Ossianix, Inc, University City Science Center, 3711 Market St, Philadelphia, PA 19014, USA. Electronic address: rutkowski@ossianix.com.
Stevenage Bioscience Catalyst · GBKing's College London · GBUniversity City Science Center · USUniversity of Maryland, Baltimore · US

Funding

Evolution of Adaptive ImmunityR01OD010549 · OD · UNIVERSITY OF MARYLAND BALTIMORE · PI FLAJNIK, MARTIN F · 2013 to 2017
$1.7M
NIH HHS R01 OD010549
6 · The paper itself

Abstract

B cell-activating factor (BAFF) plays a dominant role in the B cell homeostasis. However, excessive BAFF promotes the development of autoreactive B-cells and several antibodies have been developed to block its activity. Bispecific antibodies with added functionality represent the next wave of biologics that may be more effective in the treatment of complex autoimmune disease. The single variable domain from the immunoglobulin new antigen receptor (VNAR) is one of the smallest antibody recognition units that could be combined with monospecific antibodies to develop bispecific agents. We isolated a panel of BAFF-binding VNARs with low nM potency from a semi-synthetic phage display library and examined their functional activity. The anti-BAFF VNARs blocked the binding of BAFF to all three of its receptors (BR3, TACI and BCMA) and the presence of the conserved DXL receptor motif found in the CDR3 regions suggests molecular mimicry as the mechanism of antagonism. One clone was formatted as an Fc fusion for functional testing and it was found to inhibit both mouse and human BAFF with equal potency ex vivo in a splenocyte proliferation assay. In mice, subchronic administration reduced the number of immature and transitional intermediates B cells and mature B cell subsets. These results indicate that VNAR single domain antibodies function as selective B-cell inhibitors and offer an alternative molecular format for targeting B-cell disorders.

Indexed as

AnimalsAntibodies, BispecificB-Cell Activating FactorB-LymphocytesHumansMiceMice, Inbred C57BLMolecular MimicryPeptide LibrarySingle-Domain AntibodiesAntibodies, BispecificB-Cell Activating FactorPeptide LibrarySingle-Domain AntibodiesAnti-BAFF antibodiesB cell proliferationSingle domain antibodiesVariable domain of the immunoglobulin new antigen receptor (VNAR)

Identifiers

PMID27213814
PMCPMC5432197
OpenAlexW2398491620

What OpenQuestion holds

Textmetadata
LicenceTDM
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.