Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene pattern may identify kidney transplant recipients who don't need life-long anti-rejection drugs

25.05.2010
Researchers have identified a distinct pattern of gene expression in the largest reported group of kidney transplant recipients who have not rejected the transplant kidneys even though they stopped taking anti-rejection drugs.

This finding may help identify other transplant recipients who could safely reduce or end use of immunosuppressive therapy. In 2008, more than 80,000 people in the United States were living with a kidney transplant.

The findings come from the Immune Tolerance Network (ITN), an international research consortium supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases, of the National Institutes of Health, and the Juvenile Diabetes Research Foundation International.

The research team included three lead investigators, Kenneth Newell, M.D., Ph.D., of Emory University in Atlanta; Laurence Turka, M.D., of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston; and Vicki Seyfert-Margolis, Ph.D., the former Chief Scientific Officer of ITN and currently at the Food and Drug Administration. Their report appears online in the Journal of Clinical Investigation.

"The immunosuppressive therapy regimens that organ transplant recipients must endure have toxic side effects and increase the recipients' vulnerability to infections and cancer," says NIAID Director Anthony S. Fauci, M.D. "This study holds promise for identifying kidney transplant recipients who might be able to minimize or withdraw from their use of anti-rejection drugs. However, large, prospective studies will be necessary to determine if the same biomarkers identified in the current study are reliable predictors of immune tolerance."

Following a kidney transplant, recipients must be placed on immunosuppressive therapy or their immune systems will reject the transplanted organ. However, these drugs suppress the entire immune system, reducing an individual's ability to fight infections, and sometimes leading to diseases related to a weakened immune system, such as cancer. The drugs also have other severe side effects such as diabetes, hypertension and heart disease, as well as swelling, weight gain, and excessive hair growth and acne that many people find intolerable.

In rare cases, a physician may stop a transplant recipient's immunosuppressive drugs because of a serious medical problem such as cancer or life-threatening infection. In other cases, transplant recipients decide to reduce or stop immunosuppressive therapy against their physicians' advice, even though by doing so, they risk losing their transplanted organ. However, in a very small percentage of such cases, rejection does not occur after the drugs are stopped.

This study included 25 kidney transplant recipients who had ceased taking their immunosuppressive drugs of their own accord and yet had retained normal kidney function for more than one year. The researchers compared this group with two other groups: recipients who were still taking their immunosuppressive medication and had healthy kidneys, and healthy, non-transplant controls.

The team examined blood samples taken from participants in each of the three groups. They analyzed the gene expression of the cells in whole blood and observed that the transplant recipients who were not taking medication had a distinct pattern of genes expressed by B cells, a type of white blood cell. This pattern differed from those seen in participants who were still on immunosuppressive therapy and in non-transplant healthy control subjects. Further study identified a pattern of expression of three B cell genes that was far more common in patients who had stopped taking their medications yet maintained good graft function.

White blood cells include T and B cells. Recent studies of immune tolerance have focused on the role of a subset of T cells, called regulatory T cells (Tregs). Work in animal models indicates that B cells also may help promote immune tolerance.

"We expected to find a difference between the tolerant and immunosuppression groups in the genes associated with Tregs," says Dr. Newell. "However, we were surprised that our data showed that B cell genes may play an important role in maintaining and possibly inducing tolerance to transplanted organs."

According to Dr. Turka, identifying potential biomarkers of immune tolerance is the first step in identifying transplant recipients whose immunosuppression therapy could be reduced. "If we could develop a reliable tolerance signature—a pattern of gene expression that indicates that someone will not reject a transplant—then we could find patients who would make good candidates for supervised drug withdrawal," he said.

The study team stresses that transplant patients should never consider reducing or changing their medication regimen unless under the direct supervision of their physician. According to Drs. Newell and Turka, doing so would "almost certainly result in the rejection of the kidney, leaving the patient in need of another transplant."

Follow-up studies of this gene pattern are being planned. Similar findings already have been provided by a European group, led by King's College in London, that conducted a comparable study in kidney transplant patients. Their results appear in the same issue of the Journal of Clinical Investigation.

"The goal of ITN is to understand how immune tolerance can be induced or achieved in a variety of settings, including allergy, autoimmune disease and transplantation," says Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology and Transplantation at NIAID. "Potentially, a biomarker for tolerance in kidney transplant recipients may predict tolerance in individuals following transplantation of other organs or with other immune-mediated diseases. Having a cooperative program like ITN allows investigators to explore this possibility and apply the findings of one study across different fields of clinical research."

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

NIDDK, part of NIH, conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The Institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases. For more information, visit www.niddk.nih.gov.

The National Institutes of Health (NIH)—The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference: KA Newell et al. Characteristics of tolerant renal transplant recipients: evidence for a unique B cell signature associated with tolerance. Journal of Clinical Investigation. DOI: 10.1172/JCI39933 (2010)

Julie Wu | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Health and Medicine:

nachricht New antibody analysis accelerates rational vaccine design
09.08.2018 | Scripps Research Institute

nachricht Distrust of power influences choice of medical procedures
01.08.2018 | Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>