Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Babies with DiGeorge syndrome saved by immune supression, thymus transplant

04.08.2004


Duke University Medical Center researchers have developed a combination immune suppression and thymus transplantation technique to save infants born with complete DiGeorge Syndrome, a fatal genetic disorder.



Babies with complete DiGeorge Syndrome have no thymus, a gland important in the maturation of T cells -- specialized immune cells that help protect the body against viruses, bacteria and other pathogens. The thymus teaches T cells to fight infection while not attacking the infant’s own tissues.

Duke is the only center to offer thymus transplantation as a cure for the immune defect. Without this treatment, infants with complete DiGeorge syndrome are unable to fight off infections and will die.


Until recently, some babies with complete DiGeorge could not receive a thymus transplant because some of their bone marrow cells had spontaneously transformed into rogue T cells. These T cells attack both the body’s own tissues and foreign tissue, so thymus transplants would be rejected.

Building on 12 years of experience in treating DiGeorge syndrome, Louise Markert, M.D., associate professor of pediatrics at Duke University Medical Center, and her colleagues found that quashing the rogue T cells with an immunosuppressant drug given for three days immediately before transplant surgery resulted in successful thymus transplants. Five of six infants who underwent the new procedure survived and now live at home; one succumbed to a preexisting respiratory infection. "This really works for this population," Markert said. "It’s still experimental, but right now it’s the best option."

The immunosuppressant drug, called Thymoglobulin, only targets T cells, Markert said. "It’s less powerful than most chemotherapy. We really only need the T cells killed, and just long enough for the transplant," she said.

The transplant method and treatment results for the six infants with DiGeorge syndrome will appear in the Oct. 15, 2004, print issue of the journal Blood and are available online at the journal’s Web site, http://www.bloodjournal.org. The research was funded by the National Institutes of Health.

Not every child born with DiGeorge syndrome will need a thymus transplant. Milder forms of the disease occur in about one out of 4,000 births. Of those, only one in 250 babies -- between five and 10 each year in the U.S. -- will have complete DiGeorge syndrome with an absent thymus gland.

The disorder is often diagnosed initially by identifying birth defects characteristic of complete DiGeorge, including heart abnormalities, low calcium levels because of a missing parathyroid gland, esophageal defects and facial abnormalities such as low-set ears, wide-set eyes and a small jaw. The disorder can arise spontaneously or run in families. In less than half of cases, infants with complete DiGeorge syndrome will have a defect on chromosome 22.

Markert notes the diagnosis of complete DiGeorge has been missed in many cases because genetic testing for a defect on chromosome 22 yields a normal result, despite evidence of characteristic birth defects. This misleading finding can delay treatment, exposing an infant to risk of serious infection.

The ideal time for a thymus tissue transplant is within three months after birth, Markert said. "The key thing is to get it done before infections develop," she said.

The thymus tissue for transplant comes from tissue that would otherwise be discarded during cardiac surgery on donor infants less than six months old. Since an infant’s characteristically large thymus gland often obstructs access to the heart, in many operations surgeons must remove parts of the thymus to access the heart. Parents of the donor infants agree to donate the discarded tissue for a transplant. The clinicians culture the donor tissue for two weeks while performing testing to ensure that no diseases are transferred with the transplanted thymus tissue.

Pediatric surgeons working with Markert transplant thin strips of donor thymus tissue into a recipient infant’s thigh muscle, where it is most likely to develop a network of blood vessels to deliver nourishment and oxygen. After transplantation, immature white blood cells from the baby’s bone marrow migrate to the thymus tissue, where they are trained to differentiate between germs and the body’s own cells. About three or four months after transplantation, mature T cells emerge -- the final step toward a functioning immune system.

The transplant recipients stay in isolation rooms in Duke Hospital, either on the pediatric floor or at Duke’s General Clinical Research Center, funded by the National Center for Research Resources of the National Institutes of Health. Such isolation helps prevent infections from developing in the infant before mature T cells form.

So far, Markert has performed thymus transplants for 26 infants with complete DiGeorge syndrome, including the six who received the new immunosuppression treatment . "I learn something from each one that will make the treatment better for the next patient," she said.

Co-authors on the study include Duke colleagues Marilyn Alexieff; Jie Li; Marcella Sarzotti, Ph.D.; Daniel Ozaki; Blythe Devlin; Debra Sedlak; Gregory Sempowski, Ph.D.; Laura Hale, M.D.; Henry Rice, M.D.; Samuel Mahaffey, M.D.; and Michael Skinner, M.D.

Becky Oskin | EurekAlert!
Further information:
http://www.duke.edu
http://www.dukemednews.org

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>