The biomarkers are micro-ribonucleic acids (micro-RNAs), said Nilamadhab Mishra, M.D. He and colleagues reported at the American College of Rheumatology meeting in Washington that they had found profound differences in the expression of micro-RNAs between five lupus patients and six healthy control patients who did not have lupus.
"We are the first to show that these micro-RNAs are a problem in human lupus," said Mishra, an assistant professor of rheumatology.
Mishra said microRNAs are a class of small chains of ribonucleic acid that have important regulatory functions in the body, particularly in suppressing genes. (RNA serves as the template for translation of genes into proteins.)
The research is part of Mishra's broader focus on histones, the tiny spools in the nuclei of cells around which DNA winds and compacts when it is not in the process of copying in cell division. Changes in these histones, called epigentic changes, can alter gene expression and the proteins these genes produce without altering the underlying DNA.
In the new study, the researchers found 40 microRNAs in which the difference in expression between the lupus patients and the controls was more than 1.5 times, and focused on five micro-RNAs where the lupus patients had more than three times the amount of the microRNAs as healthy controls, and one, called miR 95 where the lupus patients had just one third of the gene expression of the microRNA of the controls.
The team reported the lesser amount of miR 95 "results in aberrant gene expression in lupus patients."
Furthermore, Mishra said, the microRNAs are associated with enzymes called histone deacetylases which provide "further rationale for the use of histone deacetylase inhibitors (HDIs) for the treatment of lupus."
Mishra has shown that HDIs reset the histone modifications. He and his colleagues are investigating two HDIs – TSA (Trichostatin A) and SAHA (suberoylanilide hydroxamic acid ) – in lupus patients and have reported positive results against a number of lupus symptoms and conditions.
Coauthors with Mishra on this study are Kerri Keiger, Ph.D., and Emmanuel Labourier, Ph.D., of Ambion Inc. in Austin, Texas, which makes RNA-based research products for the life sciences markets.
In a second presentation, Mishra discussed his hypothesis that environmental factors trigger histone modifications that activate a type of white blood cell called the B cell and turn these cells into self-destructive attackers, a key element in lupus, an autoimmune disorder.
Mishra said removing these activated B cells is one current treatment for lupus. "The lupus patients have activated B cells that cause antibody production and kidney disease, but we don't know why," he said.
But he is continuing to pursue resetting part of the epigenetic code as a way to improve lupus treatment.
"We demonstrated that the response to bacterial and viral byproducts induce B-cell activation through the epigenetic mechanism," he said. These changes lead to activation of the histone deacetylase enzymes. The HDIs stop this activation.
Robert Conn | EurekAlert!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences