Featured Research

from universities, journals, and other organizations

Promising new approach to autoimmune diseases

Date:
June 2, 2011
Source:
Harvard Medical School
Summary:
Researchers have developed a new approach for identifying the "self" proteins targeted in autoimmune diseases such as multiple sclerosis, diabetes and rheumatoid arthritis.

Researchers from Harvard Medical School and MIT have developed a new approach for identifying the "self" proteins targeted in autoimmune diseases such as multiple sclerosis, diabetes and rheumatoid arthritis.

In a paper published in Nature Biotechnology, H. Benjamin Larman and colleagues showed that errant immune responses which mistakenly target the body's own proteins rather than foreign invaders can now be examined in molecular detail. Further research could lead to new insights into the exact causes of these debilitating autoimmune disorders. The results come from the laboratory of Stephen Elledge, the Gregor Mendel Professor of Genetics and Medicine at HMS and senior author of the study.

The immune system, the body's main line of defense against disease, has a critical responsibility to distinguish self-derived proteins from those of invaders like viruses and bacteria. Autoimmune diseases arise when a person's immune system fails to make that critical distinction and mistakenly attacks a normal tissue, such as nerve, joint, or insulin-producing pancreatic cells. These disorders are usually progressive and in some cases even lead to life-threating disease. Understanding where the immune system went wrong has been a major goal for generations of biomedical researchers.

"Knowledge of the self-antigens involved in autoimmune processes is important not only for understanding disease etiology, but also for developing diagnostic tests," the authors write. "In addition, physicians may someday use antigen-specific therapies to destroy or disable auto-reactive immune cells."

But looking through the haystack of cellular complexity for those single-needle self-antigens targeted by the immune system has proved daunting, to say the least. Ideally, scientists would be to develop some kind of biological magnet that could pull these fine needles out of the mass.

In this report, the researchers describe an approach which does just that.

Elledge and colleagues improved upon a well-established technique called phage display in which bacterial viruses, called bacteriophage, display DNA-encoded protein fragments on their surfaces. As Nicole Solimini, co-corresponding author on the paper, explained, the researchers "built a reproduction of all the proteins in the human body (collectively, the human proteome) by synthesizing the corresponding DNA fragments for expression on the surface of bacteriophage."

This new proteome library provides a physical link between the protein being studied and the gene that makes it, allowing researchers to look for and identify interactions between any human proteins, such as that between an autoantibody in a patient's blood and a self-protein that prompts an autoimmune response. In fact, this technology can be used to look for any type of interaction between human proteins, providing a powerful new tool to biomedical investigators in any discipline.

Applying their technology to autoimmune disease, the team developed a technique called phage immunoprecipitation sequencing ("PhIP-Seq"). Using cerebrospinal fluid from three patients suffering from an autoimmune disorder called paraneoplastic neurological disease, the researchers could identify known and previously unreported self-proteins targeted by patients' immune systems -- that is, interactions between an autoantibody in the cerebrospinal fluid and the self-protein that drives the autoimmune response.

According to Larman, "a small sample of blood from a diabetic patient, synovial fluid from an arthritic joint, or cerebrospinal fluid from a patient with multiple sclerosis would be mixed together with the proteomic library. The self-reactive antibodies in the patient's sample will seek out and then bind to the targeted proteins in our library. We can then separate out the antibody-bound protein fragments and determine their identity by high-throughput, next-generation DNA sequencing."

Based on six years of laboratory work at HMS, the project is directly linked to the ongoing success of the Human Genome Project, which had already made available almost all of the genes the body needs in order to build, operate and repair itself. As the end products of individual genes, the body's many individual proteins are central players in all aspects of health and disease.


Story Source:

The above story is based on materials provided by Harvard Medical School. Note: Materials may be edited for content and length.


Journal Reference:

  1. H Benjamin Larman, Zhenming Zhao, Uri Laserson, Mamie Z Li, Alberto Ciccia, M Angelica Martinez Gakidis, George M Church, Santosh Kesari, Emily M LeProust, Nicole L Solimini, Stephen J Elledge. Autoantigen discovery with a synthetic human peptidome. Nature Biotechnology, 2011; DOI: 10.1038/nbt.1856

Cite This Page:

Harvard Medical School. "Promising new approach to autoimmune diseases." ScienceDaily. ScienceDaily, 2 June 2011. <www.sciencedaily.com/releases/2011/06/110602111444.htm>.
Harvard Medical School. (2011, June 2). Promising new approach to autoimmune diseases. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2011/06/110602111444.htm
Harvard Medical School. "Promising new approach to autoimmune diseases." ScienceDaily. www.sciencedaily.com/releases/2011/06/110602111444.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) — Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Reasons Why Teen Birth Rates Are At An All-Time Low

Reasons Why Teen Birth Rates Are At An All-Time Low

Newsy (Aug. 20, 2014) — A CDC report says birth rates among teenagers have been declining for decades, reaching a new low in 2013. We look at several popular explanations. Video provided by Newsy
Powered by NewsLook.com
Common Antibiotic Could Lead To Heart-Related Death

Common Antibiotic Could Lead To Heart-Related Death

Newsy (Aug. 20, 2014) — Danish researchers discovered patients taking clarithromycin have an increased risk of dying from a heart-related issue. Video provided by Newsy
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:
from the past week

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