Featured Research

from universities, journals, and other organizations

New Tool Provides Major Advance For Understanding Chronic Lyme Disease And Other Illnesses

Date:
December 1, 1999
Source:
National Institute Of Allergy And Infectious Diseases
Summary:
One of the most frustrating puzzles of Lyme disease is why some people develop debilitating chronic complications despite receiving recommended treatment. Now scientists have developed a new method to explore if these arthritic and neurologic symptoms result from the body's immune system turning against itself.

One of the most frustrating puzzles of Lyme disease is why some people develop debilitating chronic complications despite receiving recommended treatment. Now scientists have developed a new method to explore if these arthritic and neurologic symptoms result from the body's immune system turning against itself. Knowing the answer is key to developing better ways to diagnose Lyme disease, and to treat and possibly prevent its complications.

A report describing this research, led by scientists at the National Institutes of Health (NIH), appears in the December issue of Nature Medicine.

"This finding is a major advance for Lyme disease researchers and their patients," notes Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID). "We now have a powerful new tool to investigate what role autoimmune mechanisms play in the development of chronic symptoms associated with Lyme disease. We also can use this strategy to study other infectious and immunologic diseases."

Adriana Marques, M.D., of NIAID's Laboratory of Clinical Investigation, heads one of the Institute's two large studies of chronic Lyme disease and co-authored the new report.

The new technique, developed by Roland Martin, M.D., of the National Institute of Neurological Disorders and Stroke (NINDS), Richard Simon, Ph.D., of the National Cancer Institute (NCI), together with Clemencia Pinilla, Ph.D., of the Torrey Pines Institute for Molecular Studies, San Diego, was tested on a sample taken from a patient in the NIAID study. The patient has chronic central nervous system disease and a strong immune response against the Lyme agent, Borrelia burgdorferi, in both his spinal fluid and blood. Their technique identified the specific bits of the Lyme agent his T cells recognized when they mounted an immune response against the bacterium. Equally important, it pinpointed candidate self-antigens, snippets of his own cells that mimicked those recognition sites on the bacterium.

The existence of these microbial mimics does not prove they cross-react with the immune system and cause the body to turn on itself, but it is a major step in investigating that possibility. Dr. Marques and her collaborators at NIH and Tufts University's Mark Klempner, M.D., leader of the other large NIAID-supported chronic Lyme disease study, are now planning to use this method to check samples from other patients to see if they have similar autoantigen profiles. If those results look promising, further investigations can be done, including trying to recreate the autoimmune disease model in small animals.

According to the study team, their strategy opens up new avenues for understanding the immune response involved in a variety of diseases where the causative agent has not yet been identified, such as rheumatoid arthritis, diabetes or inflammatory bowel disease. It also can be used to help design novel vaccines against infectious agents and tumors, and to identify candidate self-antigens and develop ways to turn off unwanted immune responses they might generate. "We are already using this technique in our study of multiple sclerosis," notes Dr. Martin.

For the research reported here, the scientists used the T cells found in the patient's spinal fluid to probe for what might be triggering the immune response causing his disease. First, they grew T cells that reacted against a mixture of all the bacterium's proteins. Then they tested that T-cell clone against a library of 200 mixtures of peptides, small pieces of proteins made from combinations of the 20 known amino acids. Each peptide was 10 amino acids in length; one amino acid was held constant while the other nine were randomized. Next, they numerically ranked each amino acid according to the strength of the immune response it generated at each position in the peptide. Finally, they performed a computer search of three databanks-the human genome, B. burgdorferi and all known viral proteins-to find any peptide sequences that matched their most reactive peptides. This search enabled them to identify candidate antigens and self-antigens potentially implicated in the disease.

The team found that the T-cell clone recognized multiple peptides, including some derived from viruses, as well as human autoantigens potentially important in the chronic Lyme disease process. While the response of the T-cell clone to B. burgdorferi peptides was strongest, its reactivity with multiple human proteins indicates that these T cells may be continuously stimulated either by the bacterium or by the human proteins, possibly leading to autoimmune tissue damage.

The report's other co-authors are Dr. Bernhard Hemmer (now at the University of Marburg, Germany); Drs. Bruno Gran, Abraham Tzou, Takayuki Kondo, Irene Cortese, Bibiana Bielekova and Henry F. McFarland from NINDS; Dr. Yingdong Zhao from NCI; Dr. Stephen Straus from NIAID; and Drs. Jeannick Pascal and Richard Houghten from Mixture Sciences and the Torrey Pines Institute for Molecular Studies.

NIAID, NINDS and NCI are components of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NINDS is the nation's leading supporter of research on the brain and nervous system, and a lead agency in the congressionally designated Decade of the Brain. NIH is an agency of the U.S. Department of Health and Human Services.

###

References: B Hemmer, et al. Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease. Nature Medicine 5(12):1375-82 (1999).

MS Klempner and BT Huber. Is it thee or me?-autoimmunity in Lyme disease. Nature Medicine 5(12):1346-7 (1999).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.


Story Source:

The above story is based on materials provided by National Institute Of Allergy And Infectious Diseases. Note: Materials may be edited for content and length.


Cite This Page:

National Institute Of Allergy And Infectious Diseases. "New Tool Provides Major Advance For Understanding Chronic Lyme Disease And Other Illnesses." ScienceDaily. ScienceDaily, 1 December 1999. <www.sciencedaily.com/releases/1999/11/991130094015.htm>.
National Institute Of Allergy And Infectious Diseases. (1999, December 1). New Tool Provides Major Advance For Understanding Chronic Lyme Disease And Other Illnesses. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/1999/11/991130094015.htm
National Institute Of Allergy And Infectious Diseases. "New Tool Provides Major Advance For Understanding Chronic Lyme Disease And Other Illnesses." ScienceDaily. www.sciencedaily.com/releases/1999/11/991130094015.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
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
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. 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