Featured Research

from universities, journals, and other organizations

Can antibiotics cause autoimmunity?

Date:
March 31, 2014
Source:
Thomas Jefferson University
Summary:
A certain class of antibiotics prompts cells to produce low levels of novel self proteins that could trigger an autoimmune disease, research suggests. The code for every gene includes a message at the end of it that signals the translation machinery to stop. Some diseases can result from mutations that insert this stop signal into the middle of an essential gene, causing the resulting protein to be truncated. Some antibiotics cause the cell's translation machinery to ignore the stop codons and are therefore being explored as a potential therapy for these diseases.

The code for every gene includes a message at the end of it that signals the translation machinery to stop. Some diseases, such as cystic fibrosis and Duchenne muscular dystrophy, can result from mutations that insert this stop signal into the middle of an essential gene, causing the resulting protein to be truncated. Some antibiotics cause the cell's translation machinery to ignore the stop codons and are therefore being explored as a potential therapy for these diseases. But new research reported online in Proceedings of the National Academy of Sciences (the week of March 31st) shows that this approach could come with the price of triggering autoimmune disease.

"It's worth thinking about this as a potential mechanism for autoimmunity," says co-lead investigator, Laurence Eisenlohr, Ph.D., a professor in the department of Microbiology and Immunology at Thomas Jefferson University.

Autoimmune diseases such as Crohn's disease, eczema, or lupus are caused by an immune system that attacks normal components of various tissues of the body. The immune system attacks these normal tissues just as it would attack tissue infected by a bacteria or virus. What causes the immune system to malfunction in some people but not others, however, has been a puzzle. "Often, the trigger happens years before the disease has been diagnosed," says Dr. Eisenlohr.

The researchers looked at a class of antibiotics that includes gentamicin because these antibiotics have the unique property of inducing cells to read through stop codons in the genetic code -- producing a longer protein product. This mechanism can help save the translation of mutated genes whose processing is interrupted by aberrant stop codons, such as in cystic fibrosis. However, when cellular machinery reads through normal stop codons, it could create abnormally elongated proteins in the cell. Pieces of these abnormal proteins may be presented to the immune system as a part of normal protein processing, where they could be detected by the immune system. At least, that's the theory.

To test this theory, Eisenlohr's team, in collaboration with a translation biology group at the University of Utah led by Michael Howard, Ph.D., used a gene that they knew would get presented to the immune system and added a stop codon in the middle of it. They then inserted this gene into a mammalian cell line. Because the stop codon truncates the gene, normal cells did not produce the protein. However, when the researchers treated the cells with gentamicin, they began to detect the protein on the surface of cells.

While a very low number of these proteins were produced -- too little to detect by normal biochemical tests -- the T cells of the immune system are sensitive enough to pick up these miniscule amounts. Indeed, the group showed that the immune cells could detect the protein produced by gentamicin-treated cells, even at low quantities.

To test whether this process was active even in normal cells that weren't expressing an experimental gene, first author Elliot Goodenough exposed the HeLa human cell line to gentamicin and then searched for novel peptides presented on the surface of the cells. He identified 17 peptides that hadn't been characterized before in cells treated with gentamicin and showed that the peptides were presentable to the immune system. "The results suggest that gentamicin can cause cells to display novel protein fragments to the immune system," says Goodenough. In other words, "what may be garbage biologically may be important immunologically," says Eisenlohr.

However, presenting an antigen to the immune system does not guarantee that it will activate the kind of immune response that initiates autoimmunity. But because gentamicin is usually used to treat infections, "all of the right conditions are in place to potentially initiate autoimmunity," says Eisenlohr. The inflammation associated with bacterial diseases gives a signal to immune cells that the peptides they encounter are dangerous. So even as gentamicin fights the bacteria causing the infection, it also causes normal cells to produce abnormal proteins that are presented to the immune system and have a potential of initiating an autoimmune reaction.

"A number of autoimmune diseases are thought to be triggered by infections," says Eisenlohr. "The results of this study suggest that certain antibiotics used to treat those infections may also contribute to that trigger." The next steps, says Eisenlohr, could be to look at population data to see whether use of gentamicin correlates with higher rates of autoimmune diseases, as well as testing whether the peptides generated during gentamicin treatment actually do cause autoimmunity in a mouse model of the disease.


Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.


Journal Reference:

  1. E. Goodenough, T. M. Robinson, M. B. Zook, K. M. Flanigan, J. F. Atkins, M. T. Howard, L. C. Eisenlohr. Cryptic MHC class I-binding peptides are revealed by aminoglycoside-induced stop codon read-through into the 3' UTR. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1402670111

Cite This Page:

Thomas Jefferson University. "Can antibiotics cause autoimmunity?." ScienceDaily. ScienceDaily, 31 March 2014. <www.sciencedaily.com/releases/2014/03/140331153520.htm>.
Thomas Jefferson University. (2014, March 31). Can antibiotics cause autoimmunity?. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2014/03/140331153520.htm
Thomas Jefferson University. "Can antibiotics cause autoimmunity?." ScienceDaily. www.sciencedaily.com/releases/2014/03/140331153520.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins