Corporate Banner
Satellite Banner
Immunology
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Breaking the Immune System's Code

Published: Monday, November 25, 2013
Last Updated: Monday, November 25, 2013
Bookmark and Share
A diagnostic method recently developed by UC Santa Barbara can reveal the factors behind conditions thought to have environmental triggers.

By decoding an individual’s immune system, this elegant and accurate method can demystify, diagnose and provide further insight into conditions like celiac disease, multiple sclerosis, preeclampsia and schizophrenia.

“We have two goals,” said Daugherty, a researcher with the Department of Chemical Engineering at UCSB and the campus’s Center for BioEngineering. “We want to identify diagnostic tests for diseases where there are no blood diagnostics … and we want to figure out what might have given rise to these diseases.”

The process works by mining an individual’s immunological memory — a veritable catalog of the pathogens and antigens encountered by his or her immune system.

“Every time you encounter a pathogen, you mount an immune response,” said Daugherty. The response comes in the form of antibodies that are specific to the antigens — molecular, microbial, chemical — your body is resisting, and the formation of “memory cells” that are activated by subsequent encounters with the antigen. Responses can vary, from minor reactions — a cough, or a sneeze — to serious autoimmune diseases in which the body turns against its own tissues and its immune system responds by destroying them, such as in the case of Type 1 diabetes and celiac disease.

“The trick is to determine which antibodies are linked to specific diseases,” said Daugherty. Celiac disease sufferers, for example, will have certain antibodies in their blood that bind to specific peptides — short chains of amino acids — present in wheat, barley and rye. These peptides are the gluten that is the root of allergies and sensitivities in some people. Like a lock and key, these antibodies — the locks — bind only to certain sequences of amino acids that comprise the peptides — the keys.

“People with celiac disease have two particular antibody types in their blood, which have proved to be enormously useful for diagnosis,” said Daugherty.

However, sheer variety and number of antibodies present in a person’s blood at any given time has been a challenge for researchers trying to link specific illnesses with specific antibody molecules. One antigen can stimulate the production of many antibodies in response.  What’s more, each individual’s antibodies to even the same antigen differ slightly in their form. The idea of using molecular separation to find the disease antibodies has been around for over 20 years, said Daugherty, but no one had figured quite how to sift through the vast amount of molecules.

To sort through perhaps tens of thousands of antibody molecules present in a person’s blood, the research team, including postdoctoral researcher John T. Ballew from UCSB’s Biomolecular Science and Engineering graduate program, mixes a sample of a subject’s blood — which contains the antibody molecules — with a vast number of different peptides (about 10 billion).

“All the keys associate with their preferred lock,” said Daugherty. “The peptides that can bind to an antibody, do so.” The researchers then pull out the disease-bound pairs, in a process that progressively decreases the number of antibodies-peptide pairs that are most unique to a particular disease. Repeated with subsequent patients who may have the same symptoms, phenotypes or genetic dispositions, continues to whittle down the size of the peptide pool. Further in vitro evolution of the best draft peptides can identify the particular sequence of amino acid keys that fit into the antibody locks. This sequence can be used to confirm the antibodies in question as the biomarkers specifically associated with the disease.

“The diagnostic performance of the reagents generated with this approach is excellent,” said Daugherty. “We can discover biomarkers with as little as a drop of blood, and the peptides discovered can be adapted into preferred low cost testing platforms widely used in clinical practice.”

The amino acid sequence of the evolved peptides, when cross-referenced with a database of known proteins, can identify the antigens (that contain the same peptide sequence). This, in turn, can then yield clues into what factors in the patient’s environment may have contributed to the disease. The process may be used to gain insight on diseases that are thought to have environmental triggers, including Type-1 diabetes, autism, schizophrenia/bipolar disorder, Crohn’s disease, Parkinson’s disease, and perhaps even Alzheimers disease. In cases, such as Graves’ disease, where an antibody is identified as the cause (as opposed to simply an indicator) knowing the antibody’s structure can lead to more effective therapies.

“If you can get rid of the antibody, you can treat the disease,” said Daugherty. “By finding these keys, you can block the antibody.”

Research on this study was performed also by partners from the Mayo Clinic; the University of Tampere in Finland; UC San Diego; and Seinäjoki Central Hospital in Finland. Their findings are published in a paper titled “Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes,” in the Nov. 11 online issue of the Proceedings of the National Academy of the Sciences.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Childhood Cancer Cells Drain Immune System’s Batteries
Cancer cells in neuroblastoma contain a molecule that breaks down a key energy source for the body’s immune cells, leaving them too physically drained to fight the disease.
Researchers Discover Immune System’s 'Trojan Horse'
Oxford University researchers have found that human cells use viruses as Trojan horses, transporting a messenger that encourages the immune system to fight the very virus that carries it.
Researchers Discover New Type of Mycovirus
Virus infects the fungus Aspergillus fumigatus, which can cause the human disease aspergillosis.
How to Become a Follicular T Helper Cell
Uncovering the signals that govern the fate of T helper cells is a big step toward improved vaccine design.
Sorting Through Cellular Statistics
Aaron Dinner, professor in chemistry, and his graduate student Herman Gudjonson are trying to read the manual of life, DNA, as part of the Dinner group’s research into bioinformatics—the application of statistics to biological research.
Women’s Immune System Genes Operate Differently from Men’s
A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.
Experimental MERS Vaccine Shows Promise in Animal Studies
A two-step regimen of experimental vaccines against Middle East respiratory syndrome (MERS) prompted immune responses in mice and rhesus macaques, report National Institutes of Health scientists who designed the vaccines.
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!