Navigation Links
A promising new approach to autoimmune diseases
Date:6/2/2011

BOSTON 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 systemsthat 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.


'/>"/>

Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

Related biology news :

1. Several abstracts on gout reveal true burden of disease and highlight promising new treatments
2. Celiac disease vaccine shows promising results in Phase I trial
3. Study identifies promising target for AIDS vaccine
4. New cell therapy a promising atherosclerosis treatment
5. Antifungal compound found on tropical seaweed has promising antimalarial properties
6. Alfred P. Sloan Foundation honors promising young scholars
7. Using a childs own stem cells to repair their heart looks promising
8. Graphene and spintronics combo looks promising
9. Early investigations promising for detecting metastatic breast cancer cells
10. Early safety results promising for Phase I/II trial of gene therapy treatment of hemophilia B
11. Tufts University chemist earns prestigious award for promising research on drug development
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/22/2017)... , March 21, 2017 Optimove ... used by retailers such as 1-800-Flowers and AdoreMe, ... — Product Recommendations and Replenishment. Using Optimove,s machine learning ... personalized product and replenishment recommendations to their customers ... on predictions of customer intent drawn from a ...
(Date:3/13/2017)... March 13, 2017 Future of security: Biometric Face Matching ... ... DERMALOGs Face Matching enables to match face pictures against each ... to identify individuals. (PRNewsFoto/Dermalog Identification Systems) ... DERMALOG,s "Face Matching" is the fastest software for biometric Face Matching on ...
(Date:3/6/2017)... , March 6, 2017 Mintigo ... technology, today announced Predictive Sales Coach TM , ... actionable sales intelligence into Salesforce. This unique AI ... their sales organizations with deep knowledge of their ... for intelligent engagement. Predictive Sales Coach extends Mintigo,s ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... ... ... proud to announce it has become the premiere team-building cooking event company in San Diego. ... such as Illumina, HP and Qualcomm, and is ranked #1 in its category on Trip ... its new team building format, a way for teams to not only interact with one ...
(Date:3/23/2017)... Calif., March 23, 2017  BioPharmX Corporation (NYSE ... for the dermatology market, today reported financial results ... 2017, and will provide an update on the ... year. "We are pleased to report ... for BioPharmX," said President Anja Krammer. "We achieved ...
(Date:3/23/2017)... , March 23, 2017  Agriculture technology company ... A financing and note conversion to commercialize its Cool ... is focused on developing products that are simultaneously profitable ... million in the last 18 months. This latest round ... Bridge Venture Partners. The company,s primary ...
(Date:3/22/2017)... 22, 2017  Ascendis Pharma A/S (Nasdaq: ASND), ... technology to address significant unmet medical needs in ... full year ended December 31, 2016. ... company as we broadened our pipeline and pursued ... disease company with an initial focus on endocrinology," ...
Breaking Biology Technology: