hh.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A transcriptional regulator controlling severity in experimental arthritis
Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS). Department of Drug Design and Pharmacology, Copenhagen University, Copenhagen, Denmark.ORCID iD: 0000-0003-4360-7710
Nordic Bioscience, Copenhagen, Denmark.
2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, no Suppl. 2, p. 667-667, article id FRI0011Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Background: Susceptibility to Rheumatoid Arthritis (RA) is dependent on complex interactions among genetic and environmental factors. Protein candidates and their role in pathways leading to chronic inflammation of the joints, in addition to their potential as drug targets, can be revealed with the help of experimental models for disease (1). From the results of functional genetic studies, we have recently shown that the T-box gene, TBX3, is a candidate gene in Collagen Induced Arthritis (CIA), an experimental model for RA (2). TBX3 encodes a transcriptional regulator involved in differentiation of several organs, including bone, during embryonic development. It has, in addition, been demonstrated important in oncogenesis (3). Our studies suggest that TBX3 has a role in B-cell activation and is important for the severity of disease in the CIA model (2). Objectives: The objective of this project is to understand the role for the transcriptional regulator TBX3 in development of RA. Methods: Bioinformatics based comparative studies of mouse and human alleles in the regulatory region of TBX3. CRISPR/Cas9-introduced deletions and base modifications in human B-cell lines. Activation of genetically modified B-cells in vitro, followed by analyses of proliferative response and antibody production. Results: Studies of CIA development in mice with single nucleotide polymorphisms (SNPs) in the regulatory region of Tbx3 revealed a significant difference in severity of arthritis. In line with this, the anti-collagen type II antibody titers were shown substantially higher in mice with more severe arthritis, even before onset of disease. In addition, preliminary data shows that the proliferative response to Type II collagen upon re-challenge of lymph node cells in vitro is higher in these mice, suggesting a more active response to the disease-inducing antigen. Because the TBX3 gene is conserved between mouse and human, we are investigating whether similar genetic variations are found in the regulatory region of the human TBX3 gene and whether the putative genetic variation would lead to a distinct B-cell phenotype upon activation in vitro. Conclusion: We suggest that the oncoprotein TBX3 is a novel candidate contributing to disease severity in experimental arthritis. Investigations of genetic variation in the TBX3 gene and its role in the activation of human B-cells will reveal whether this protein is a candidate for influencing also development of RA.

Place, publisher, year, edition, pages
London, UK: BMJ Publishing Group Ltd, 2019. Vol. 78, no Suppl. 2, p. 667-667, article id FRI0011
Keywords [en]
Rheumatoid Arthritis, Collagen-induced arthritis, TBX3, transcriptional regulator, biomarker
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:hh:diva-39950DOI: 10.1136/annrheumdis-2019-eular.7057ISI: 000472207102055OAI: oai:DiVA.org:hh-39950DiVA, id: diva2:1328843
Conference
Annual European Congress of Rheumatology, EULAR 2019, Madrid, Spain, June 12-15, 2019
Available from: 2019-06-23 Created: 2019-06-23 Last updated: 2019-09-10Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Authority records BETA

Andersson, Åsa

Search in DiVA

By author/editor
Andersson, Åsa
By organisation
The Rydberg Laboratory for Applied Sciences (RLAS)
In the same journal
Annals of the Rheumatic Diseases
Immunology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 119 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf