Note: This review is based upon a presentation at the 2014 American Society of Hematology (ASH) Annual Meeting, December 6 - 9 in San Francisco, CA.The full abstract may be reviewed on the ASH Annual Meeting Web site.
Kohei Hosokawa, M.D., Ph.D.; Pawel Muranski, M.D.; Xingmin Feng, Ph.D.; Keyvan Keyvanfar; Danielle M. Townsley, M.D.; Bogdan Dumitriu, M.D.; Jichun Chen, Ph.D.; Sachiko Kajigaya, Ph.D.; James G. Taylor, M.D.; Christopher S. Hourigan, M.D., Ph.D.; John Barrett, M.D.; and Neal S. Young, M.D.
Abstract 2940: Altered microRNAs in T cells from Patients with Acquired Aplastic Anemia
MicroRNAs (miRNAs) are small molecules that block the production of proteins from messenger RNA, which contains the genetic coding information needed to make proteins. These miRNAs might control the immune system’s defense against foreign substances. The role of miRNAs in aplastic anemia has not previously been studied.
A research team studied the signatures of miRNA in samples of CD4+ and CD8+ T cells (part of the immune system) from people with aplastic anemia. Their main goal was to identify new genes that help regulate the immune system’s response in aplastic anemia. The researchers compared these samples to cells from healthy people and from patients with MDS or sickle cell disease.
- miRNAs were downregulated, meaning that they had less ability to turn genes on and off, in the CD4+ and CD8+ T cells of patients with all of the diseases studied than in healthy volunteers.
- Expression levels (use of information in genes to control the formation of proteins) of four miRNAs—126-3p, 145-5p, 223-3p and 199a-5p—were three times lower in the CD4+ and CD8+ T cells of patients with aplastic anemia than in healthy patients or patients with the other diseases studied.
- Treatment to suppress immune system response doubled the expression levels of miRNAs 126-3p and 145-5p in six patients with aplastic anemia.
- Reducing the expression of miRNAs 126-3p and 145-5p increased the growth of both CD4+ and CD8+ T cells and the production of interferon-gamma, which helps the body resist cancer, in CD8+ T cells.
- This study helped determine the previously unknown potential role of miRNAs 145-5p and 126-3p in T cell activation in aplastic anemia.
- Understanding the functions of these miRNAs might lead to the development of new treatments for aplastic anemia.
- Further research needs to determine the role of these miRNAs in the more general development of autoimmune diseases.