Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Studies of liver transplant patients off anti-rejection drugs have altered cell profile

03.06.2003


University of Pittsburgh researchers report results in American Journal of Transplantation and at American Transplant Congress, suggesting blood test to determine who can be weaned not far off



Liver transplant patients who are off all immunosuppression and those who are undergoing withdrawal of their anti-rejection drugs have higher concentrations of a special immune system cell than those patients who have failed attempts at weaning or who have a history of organ rejection, report University of Pittsburgh researchers. Those off drugs have the same cellular profile as normal, healthy volunteers, who the researchers also studied.

Results of the study are published in the June issue of the American Journal of Transplantation and are being presented today at the American Transplant Congress, the joint scientific meeting of the American Society of Transplant Surgeons and the American Society of Transplantation running through June 4 at the Marriott Wardman Park Hotel in Washington, D.C.


The researchers hope the findings will bring them one step closer to developing a simple blood test predictive of transplant tolerance – the immune system’s full acceptance of a transplanted organ – and of which patients can be successfully weaned off all drugs. However, the researchers caution that further studies will be needed to verify their results.

"Developing such a test or series of tests would be of considerable value in identifying those patients who might be safely weaned off anti-rejection therapy. Our finding a higher incidence of a subtype of a certain dendritic cell in our weaned and nearly weaned patients is a positive step toward this goal," said lead author George Mazariegos, M.D., associate professor of surgery at the Thomas E. Starzl Transplantation Institute and the University of Pittsburgh School of Medicine.

Looking for the presence of different kinds of dendritic cells, the researchers found that patients off all anti-rejection drugs and those in the process of drug withdrawal had significantly more of a beneficial kind of dendritic cell and fewer numbers of the more harmful dendritic cells, a cellular profile that was similar to normal, healthy non-transplant patients who served as a control group. Compared to those who required daily doses of anti-rejection drugs – those who failed at being weaned or who had a history of rejection episodes – the patients off drugs or nearing that target also had a much higher ratio of the good cells to bad cells.

These so-called beneficial dendritic cells are immature or precursor dendritic cells that derive from plasmacytoid T cells (pDC2). While dendritic cells, a rare type of white blood cell that is present in all tissues, are usually known for their ability to identify and present antigens, or foreign substances, to other immune system cells that are programmed to destroy the antigen, not until recently did researchers identify subtypes like the pDC2 that have the opposite effect. These appear to regulate the immune response and determine that a frontline attack against the organ by T cells is unwarranted. "It is quite exciting to identify the presence of this dendritic cell subtype, which we have noted in laboratory models, in patients who by virtue of their being off immunosuppression are tolerant of their transplanted organs," stated Angus Thomson, Ph.D., D.Sc., professor of surgery and immunology at the Thomas E. Starzl Transplantation Institute and University of Pittsburgh School of Medicine, and senior author.

The published pilot study involved six patients who had been weaned for a mean of 3.3 years, the longest for nearly eight years. Of these, two had been weaned through a physician-controlled protocol, three were taken off the drugs because of serious infectious disease concerns, and one patient had stopped taking the drugs on his own. A second group of patients consisted of 23 patients undergoing the weaning process, and the third group was comprised of 11 patients taking maintenance doses of immunosuppression. Six of these 11 had failed at weaning and five had a history of rejection episodes. Thirteen healthy non-transplant patients served as controls.

At ATC, Dr. Mazariegos is reporting update results that were obtained in eight weaned patients, 26 patients in the process of being weaned and 16 patients who required maintenance immunosuppression. Of the weaned patients, three were taken off for emergent reasons, three were weaned through the protocol and two were noncompliant patients who stopped on their own.

According to the authors, their findings involving dendritic cells, and those published by the team last year that looked at genetic profiles of key regulatory proteins that regulate the immune system, are the first to definitively give clues to the make-up of patients who are able to be off all immunosuppression.

"While the initial results indicate there may be some correlation with the presence of ’good dendritic cells’ and immune unresponsiveness, a longer, more complete investigation must now be performed if these cells are to be validated as a surrogate marker of tolerance," said Terry Strom, M.D., co-chair of the Immune Tolerance Network (ITN) Assay Group.

To determine the validity of the dendritic cell profile as a possible test to predict successful weaning, the researchers plan to examine a larger group of liver transplant patients in whom weaning is being considered.

Typically, a life-long regimen of anti-rejection drugs is required to prevent the transplanted organ from being attacked by the patient’s immune system. Such drugs can cause serious complications, such as tumor growth, and make patients more susceptible to infections. The risks associated with long-term immunosuppressive therapies are one of the key limiting factors of successful organ transplantation.

This study was performed as a project of the ITN, a seven-year clinical research project headquartered at the University of California, San Francisco and supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation.

Dr. Thomson is principal investigator of the Pittsburgh-based ITN study and Dr. Mazariegos is a co-investigator. Other researchers include Adriana Zeevi, Ph.D., co-principal investigator, and Jorge Reyes, M.D., a co-investigator.


CONTACT:
Lisa Rossi (cell 412-916-3315)
Michele Baum
PHONE: 412-647-3555
FAX: 412-624-3184
E-MAIL:
RossiL@upmc.edu
BaumMD@upmc.edu

Lisa Rossi | EurekAlert!
Further information:
http://www.upmc.edu/

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

Smart Computers

21.08.2017 | Information Technology

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>