Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecule expressed early in pregnancy may help patients tolerate transplants

15.10.2003


Transplant surgeon Oscar H. Grandas (left) and reproductive immunologist Anatolij Horuzsko are looking at a molecule expressed early in pregnancy that may provide a better way to help transplanted organs survive.



A molecule expressed in the earliest stages of pregnancy that vanishes when the baby is born seems to keep some cells responsible for directing the immune system in an immature and accepting stage, Medical College of Georgia researchers says.

Their finding that the molecule HLA-G helps make dendritic cells – which work like air-traffic controllers for the immune system – tolerant helps explain how a fetus, with genes from both parents, can avoid rejection by the mother’s immune system.

And it has them optimistic that the natural mechanism could be replicated to help preserve a transplanted heart or kidney.



"These immature dendritic cells can induce suppressor cells that will suppress the immune response," said Dr. Anatolij Horuzsko, reproductive immunologist. He is principal investigator on a $ 1.3 million grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to explore whether this selective immune suppression – which occurs in the placenta where mother and developing baby touch – can help transplant patients avoid rejection without putting them at risk for new infection and disease.

Dr. Horuzsko and his co-investigator Dr. Oscar H. Grandas, transplant surgeon, say it’s a logical pursuit because a fetus is essentially a transplant in which, for nine months, a developing body containing genetically foreign material – the half he gets from his father – often escapes rejection by the mother’s immune system. It’s believed that some lost pregnancies result when, for some reason, localized suppression doesn’t happen.

Amazingly there is evidence that in some transplant patients natural suppression also occurs.

Some of the many questions Drs. Horuzsko and Grandas want to answer are, ’Is the spontaneous suppression mechanism that occurs in some patients the same one that occurs during pregnancy?’ and ’Can they make the suppression happen for all patients?’

Dr. Horuzsko has found that HLA-G binds with the inhibitory receptor on the surface of dendritic cells, leaving the cells, at least for a time, immature and tolerant. In research, published in 2002 in the European Journal of Immunology, he performed skin grafts on transgenic mice which express HLA-G and found some of the dendritic cells oddly changed and nonresponsive, a state which enabled the skin grafts to survive about a month longer than those on normal mice. The human equivalent likely would be much longer since a day in a mouse’s life translates to about a month for a human.

This mechanism provides a targeted escape from the usual rigorous patrol of the immune system. HLA-G is an antigen, which is a substance that gets the attention of the immune system; good antigen matches are desirable between an organ donor and transplant recipient because it reduces the risk of rejection. A fetus and a donated organ have much in common; both logically would be viewed by the immune system as foreign bodies that need elimination because both would have foreign antigens.

"From a transplant point of view, this is a huge problem that we have," Dr. Grandas said. "We don’t know who we need to immunosuppress," he said, referencing studies such as a recent one at the University of Pittsburgh that showed that as many as 70 percent of recipients don’t reject their transplanted organs even though they are on minimal immunosuppressive therapy. "What that is telling me is there are people who reject and people who do not and we don’t know why or how to tell who is who. Those are two big areas I have interest in. One is trying to identify the rejecters versus non-rejecters. The second is how can we modify human or animal dendritic cells in order to induce tolerance then wean transplant recipients from immunosuppression to see if we can prolong graft survival," Dr. Grandas said.

The ability to identify the best matches for patients has improved and the drugs patients take to avoid rejection have as well, Dr. Grandas said of the last 20 years in the transplant field. Ironically the net effect has been that acute rejection rates of grafts, or transplanted organs, have dramatically dropped but many organs are still failing over time.

"Even though the organ is not rejected, they are failing for other reasons," Dr. Grandas said. "Patients get infected and die with a working graft or they develop chronic graft dysfunction," because the drugs given to help the graft survive generally suppress the immune system, leaving patients more vulnerable to infection and disease.

So he collaborates with Dr. Horuzsko to test his findings about HLA-G and immature dendritic cells to see if they can create this scenario in animal models with the goal of eventually moving the work to patients.

In the lab, Dr. Grandas is doing islet cell transplants – which include the insulin-producing beta cells of the pancreas - to cure diabetes in rats. With his new NIH grant, Dr. Horusko is going to use HLA-G to modify the dendritic cells of the donor animal then inject them into the recipient rat before Dr. Grandas does the transplant.

Aware that there are likely other factors involved, he will also remove from the recipient some lymphocytes, cells of the immune system that already are programmed for cuing rejection. Transplant patients already get medication to do the same thing. "We will be giving a double whammy of lymphocytic depletion plus dendritic cell injection," said Dr. Horusko.

One of the many difficulties will be finding the optimal mechanism for inducing the desired, localized suppression. "I believe the future will be injection of a few cells to induce a specific mechanism to create only that and not touch anything else," Dr. Horuzsko said.

Dr. Grandas believes he is correct because patients would get donor-specific dendritic cells with the same antigen makeup as the organ they receive. "So you will have donor-specific induction of inhibitory cells," Dr. Grandas said.

"This is a goal because the patient needs to fight infection and, in this case, the immune system will be ready to do that and be tolerant of the transplant only," Dr. Horuzsko said.

The transplant surgeon noted that the approach other groups in the country are using is total bone marrow transplants in conjunction with organ transplants, which means replacing all components of the immune system plus components for blood production. "We think Dr. Horusko’s approach is a step ahead because you will infuse only a particular subset of cells that have the function we want regulated," Dr. Grandas said.

Toni Baker | EurekAlert!

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

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: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>