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!
Usher syndrome: Gene therapy restores hearing and balance
25.09.2017 | Institut Pasteur
MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve University
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy