news
Finnish researchers have found that an accumulation of gene mutations, similar to those typically seen in the development of cancer, also occur in some patients with rheumatoid arthritis.
Gene mutations that accumulate in somatic cells have a significant impact on the development of cancer, yet no studies on their involvement in the pathogenesis of autoimmune diseases have previously been conducted. A research project conducted in cooperation by the University of Helsinki and the Helsinki University Central Hospital found that somatic mutations were also present in patients with rheumatoid arthritis.
Published in the Nature Communications journal, the study found mutations in genes important to the immune defence system in white cells separated from blood samples taken from patients recently diagnosed with rheumatoid arthritis.
It may be possible that these mutations affect the regulation of the inflammatory process, says Satu Mustjoki, a research professor at the Finnish Cancer Institute and the University of Helsinki.
Altogether 85 patients with recently diagnosed rheumatoid arthritis participated in the study, in addition to which there were 20 healthy control subjects. By utilising the latest deep sequencing techniques, the researchers identified mutations in one fifth of the patients. All identified mutations were located in cells known as killer cells, or cytotoxic CD8+ T cells. No mutations were found in helper cells, or CD4+ T cells.
One somatic mutation was found in a single healthy control subject, which means that the finding is not entirely arthritis specific, notes Professor Marjatta Leirisalo-Repo, a specialist in rheumatology.
The ability found in T cells to recognise countless different protein structures inherent in, for example, pathogens, is based on their versatile selection of T cell receptors. This selection is formed in the thymus, where gene stubs that code the T cell receptors found in T cells are split and rearranged into functioning receptors. Thus, the surface of each new T cell is imbued with a unique T cell receptor.
When the immune defence system is activated, T cells multiply exponentially while identical T cells form cell clones that can be identified by the rearrangement of their shared, unique T cell receptor.
Enlarged T cell clones were found in all patients with rheumatoid arthritis concomitant with somatic mutations. Further investigation proved that the mutations were limited to these enlarged cell clones.
This indicates that mutations are formed only in mature T cells, not at the stem cell level, say BM Paula Savola and PhD Tiina Kelkka, the main authors of the article. If mutations were formed at the earlier differentiation stage, they would have been present in CD8+ T cells and CD4+ helper cells expressing other T cell receptor types as well.
The mutations were found to be permanent, since identical clones and mutations were found in the patients white blood cells several years after the original finding.
For now, there is no certainty on how these mutations affect the regulation of chronic inflammations. They may be, for lack of a better word, genomic scars formed as a result of the activation of the immune defence system, says Mustjoki.
In any case, this research project revealed a new connection on the molecular level between autoimmune diseases and cancer, which brings us one step closer to understanding these diseases.
The starting point for this project was earlier findings related to LGL leukaemia made by Mustjokis research group. In LGL leukaemia, somatic mutations often found in the STAT3 gene and located also in the cytotoxic T cells of patients cause a slowly progressing blood disorder, in addition to which they predispose patients to autoimmune diseases. The most common autoimmune disease related to LGL leukaemia is rheumatoid arthritis.
In the future, we intend to study the prevalence of this phenomenon in other inflammatory conditions and the practical significance of these mutations as regulators of inflammatory reactions, says Mustjoki.
Researchers from the Faculty of Medicine at the University of Helsinki, the Institute for Molecular Medicine Finland, the Blood Service and the Departments of Rheumatology and Hematology at the Helsinki University Hospital participated in the research project. The project was led by Professors Satu Mustjoki, Marjatta Leirisalo-Repo and Kimmo Porkka.
Funding for the project was provided, among others, by the Academy of Finland and the European Research Council.
Follow this link:
New gene mutations found in white blood cells in rheumatoid arthritis patients - Drug Target Review
- Podcast 9 Athens part 3 and news [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Podcast 10 Athens part 4 [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Podcast 11 Athens Part 5 [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 12 Cardiac Nuclear Medicine in the UK [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Podcast 13 Choline PET and prostate cancer [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode14 ED function and Dysponea [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- ep 15 Collimator Choice and Reconstruction algorithm [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 16 Dr Strauss on vulnerable plaque [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode17 Chemical Stress [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 18 Myocardial Perfusion Imaging and Diabetes [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 19 The INSPIRE trial [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- 20 Dual isotope with a difference [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 21 The real effect of stress [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 22 D-SPECT [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 23 VQ Reprise [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 24 Hepatobiliary Nuclear Medicine [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 25 Sleep Apnea [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 26 Imaging Post Traumatic Stress Disorder [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 27 Cardiac Stem Cells [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 28 Molly Supply [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 29 Melanoma therapy interview with Dr Ekaterina Dadachova [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 30 Viral Therapy [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 31 breast radiotherapy using radioisotopes [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 32 news from snm [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 33 EBV Imaging and Therapy [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Episode 34 Dr Lele SNM India 2009 [Last Updated On: December 14th, 2009] [Originally Added On: December 14th, 2009]
- Episode 35 Dr Andrew Scott from the Ludwig institute [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- Episode 36 CardiArc [Last Updated On: February 25th, 2010] [Originally Added On: February 25th, 2010]
- Episode 37 Dr Modder Radiosynoviorthesis (Radiation Synovectomy) [Last Updated On: March 31st, 2010] [Originally Added On: March 31st, 2010]
- Episode 38 Indian Nuclear Medicine With Dr Malhotra and Dr Krishna [Last Updated On: May 28th, 2010] [Originally Added On: May 28th, 2010]
- Episode 39 Prof Ora Israel The Utility of Hybrid Imaging [Last Updated On: July 13th, 2010] [Originally Added On: July 13th, 2010]
- Episode 40 New V/Q SPECT developments [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- Episode 41 scintimun [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- Episode 42 Radio-Isotope Supply into the future [Last Updated On: March 6th, 2011] [Originally Added On: March 6th, 2011]
- Podcast 4: DNA therapy [Last Updated On: April 24th, 2011] [Originally Added On: April 24th, 2011]
- Sorry about the delay a new podcast will be out soon! [Last Updated On: April 24th, 2011] [Originally Added On: April 24th, 2011]
- Podcast 5 Flash 3D [Last Updated On: April 24th, 2011] [Originally Added On: April 24th, 2011]
- Podcast 6 Affibody [Last Updated On: April 24th, 2011] [Originally Added On: April 24th, 2011]
- Podcast 7 EANM 2006 Athens Part 1 [Last Updated On: April 24th, 2011] [Originally Added On: April 24th, 2011]
- Podcast 8 Athens Part 2 [Last Updated On: April 24th, 2011] [Originally Added On: April 24th, 2011]
- Episode 43 Rapidscan Part 1, 720P high quality video version [Last Updated On: May 1st, 2011] [Originally Added On: May 1st, 2011]
- Episode 43 Rapidscan Part 1, Ipod quality video [Last Updated On: May 1st, 2011] [Originally Added On: May 1st, 2011]
- Episode 43 Rapidscan Part 1, Audio version [Last Updated On: May 1st, 2011] [Originally Added On: May 1st, 2011]
- Episode 45 Mummies with cardiovascular disease video [Last Updated On: May 21st, 2011] [Originally Added On: May 21st, 2011]
- Episode 45 Mummies with cardiovascular disease audio edition [Last Updated On: May 21st, 2011] [Originally Added On: May 21st, 2011]
- Episode 46 Dr Gordon DePuey Choosing Reconstruction clinical perspective [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- Episode 46 Dr Gordon DePuey Choosing Reconstruction clinical perspective audio version [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- Episode 47 Cardiac Image Fusion With Dr Kaufmann [Last Updated On: September 18th, 2011] [Originally Added On: September 18th, 2011]
- Episode 47 Cardiac Fusion with Dr Kaufmann video version [Last Updated On: September 18th, 2011] [Originally Added On: September 18th, 2011]
- Dear Steve, I am and many more like me are your one more thing. [Last Updated On: October 9th, 2011] [Originally Added On: October 9th, 2011]
- EPISODE 48 PET MRI camera from Siemens with Dr Georgi audio [Last Updated On: October 23rd, 2011] [Originally Added On: October 23rd, 2011]
- EPISODE 48 PET MRI camera from Siemens Dr Georgi video [Last Updated On: October 23rd, 2011] [Originally Added On: October 23rd, 2011]
- Silicon Biosystems to Present Single-Circulating Tumor Cell Molecular Characterization at the Fourth World CTC Summit [Last Updated On: April 25th, 2012] [Originally Added On: April 25th, 2012]
- Leukaemia cells have a remembrance of things past [Last Updated On: April 25th, 2012] [Originally Added On: April 25th, 2012]
- Technologist Education Requirements Can Help Cut Repeat Scans [Last Updated On: April 25th, 2012] [Originally Added On: April 25th, 2012]
- HKU Collaborative Research Discovers A Novel Molecular Mechanism Of A New Anti-HIV-1 Drug Candidate [Last Updated On: April 25th, 2012] [Originally Added On: April 25th, 2012]
- Focal Segmental Glomerulosclerosis and the Nephrotic Syndrome - Part 1 Clinical - Video [Last Updated On: May 4th, 2012] [Originally Added On: May 4th, 2012]
- Electro-Medicine : Biological Physics - The Molecular Basis of Alzheimers Disease - Video [Last Updated On: May 4th, 2012] [Originally Added On: May 4th, 2012]
- osdd heterocyclic compounds and molecular medicines - Video [Last Updated On: May 4th, 2012] [Originally Added On: May 4th, 2012]
- Molecule to Medicine: The Biomarker Frontier - Video [Last Updated On: May 4th, 2012] [Originally Added On: May 4th, 2012]
- Fulfilling the Promise of Molecular Medicine in a Developmental Brain Disorder - Video [Last Updated On: May 4th, 2012] [Originally Added On: May 4th, 2012]
- Focus on Stefanie Dimmeler - Video [Last Updated On: May 4th, 2012] [Originally Added On: May 4th, 2012]
- Dundee [Last Updated On: May 4th, 2012] [Originally Added On: May 4th, 2012]
- Nanotechnology In Medicine: Huge Potential, But What Are The Risks? [Last Updated On: May 5th, 2012] [Originally Added On: May 5th, 2012]
- Cutting Edge Technology Coming To DMH [Last Updated On: May 5th, 2012] [Originally Added On: May 5th, 2012]
- This Week in Experimental and Molecular Pathology [Last Updated On: May 5th, 2012] [Originally Added On: May 5th, 2012]
- Researchers' discovery offers hope for cancer, heart disease miracle drugs [Last Updated On: May 7th, 2012] [Originally Added On: May 7th, 2012]
- Penn State student Zachary Hostetler from Garnet Valley is being honored as a student marshal [Last Updated On: May 7th, 2012] [Originally Added On: May 7th, 2012]
- NCKU Student Wins Prestigious Award for Anti-Cancer Research [Last Updated On: May 10th, 2012] [Originally Added On: May 10th, 2012]
- In-Vitro Diagnostics (IVD) Market (Clinical Chemistry, Immunoassays, Molecular Diagnostics, Hematology Analyzers ... [Last Updated On: May 10th, 2012] [Originally Added On: May 10th, 2012]
- Pitt team uses genomics to identify a molecular-based treatment for a viral skin cancer [Last Updated On: May 10th, 2012] [Originally Added On: May 10th, 2012]
- Genomics used to identify a molecular-based treatment for a viral skin cancer [Last Updated On: May 10th, 2012] [Originally Added On: May 10th, 2012]
- 2 molecular biologists get $500K medical prize [Last Updated On: May 13th, 2012] [Originally Added On: May 13th, 2012]
- 2 molecular biologists share $500K medical prize [Last Updated On: May 13th, 2012] [Originally Added On: May 13th, 2012]
- Lab21 Unveils New Molecular Analysis Services at Greenville Site [Last Updated On: May 13th, 2012] [Originally Added On: May 13th, 2012]
- 2 molecular biologists from NYC to share $500K medical prize for pioneering research on cells [Last Updated On: May 13th, 2012] [Originally Added On: May 13th, 2012]
- Two Molecular Biologists Get $500K Medical Prize [Last Updated On: May 13th, 2012] [Originally Added On: May 13th, 2012]
- Pair of molecular biologists receive Albany Medical Center Prize [Last Updated On: May 13th, 2012] [Originally Added On: May 13th, 2012]
- CNIO scientists successfully test the first gene therapy against aging-associated decline [Last Updated On: May 16th, 2012] [Originally Added On: May 16th, 2012]
- Cancer Institute of New Jersey Aims to Advance Personalized Cancer Treatments Through 'Precision Medicine' [Last Updated On: May 16th, 2012] [Originally Added On: May 16th, 2012]