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 April 18, 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 April 18, 2014).

Share This



More Health & Medicine News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. 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