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Thymus Transplant Might Save Babies Born Without Immune Systems

Published July 24, 2003 | Updated January 20, 2016

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Duke Health News919-660-1306

Durham, NC -- Babies destined to die because they were born without
a thymus -- the organ that generates immune cells -- can be given
lifesaving tissue normally discarded during cardiac surgery on other
infants, researchers have found.

Duke University Medical Center
physicians have reported in the Aug. 1, 2003 issue of the journal
Blood, successfully treating the immune disorder complete DiGeorge
Syndrome in seven of 12 children who underwent an experimental thymus
transplantation procedure. As many as one in 4,000 children in the
United States are born each year with varying degrees of DiGeorge
Syndrome, a condition in which the body does not produce adequate
quantities of T cells, the cells that help the body fight infections.
Between five and 10 children are born in the United States each year
with complete DiGeorge Syndrome, a condition in which babies' immune
systems do not develop at all because they are born without a thymus.

All
12 patients in the Duke study were diagnosed with complete DiGeorge
Syndrome. The 12 children were treated between 1993 and 2001 at Duke
University Medical Center, the only center in the world currently
offering the experimental thymus transplantation procedure.

The
thymus rests on the heart and functions as a "schoolhouse" for immune
cells. As cells pass through the thymus they are trained to become T
cells, white blood cells that fight infection. A person without a
thymus does not produce these T cells and, therefore, is at great risk
for developing infections. By the time humans reach puberty, the thymus
has completed most of its role in the body, shrinks in physical size
and becomes dormant.

Without intervention, few children with
complete DiGeorge Syndrome live to age 1, and none survive past 3 years
of age. The seven surviving Duke patients are all well and living at
home two to 10 years after receiving their transplants. Five patients
in this study died, all from underlying congenital problems.

"Children
born with complete DiGeorge Syndrome often face a host of medical
challenges that can include heart problems, developmental disorders and
deafness, but without treatment, infection resulting from immune
deficiency is by far the factor that most often causes these children
to die," said Louise Markert, M.D., associate professor of pediatrics
at Duke University Medical Center, and lead author of the study.

Markert
and colleagues have pioneered the procedure to transplant thymus tissue
into babies with DiGeorge Syndrome to enable their bodies to learn to
fight infection. "Implanting thymus tissue early enough in life can
provide these children with a chance to create a new immune system,"
said Markert.

Transplantation is made possible because a small
amount of thymus tissue is ordinarily discarded during neonatal heart
surgeries. It must be excised in order for surgeons to expose the
heart. Markert asks parents of babies undergoing heart surgery for
permission to use any discarded thymus tissue to help a child with
DiGeorge Syndrome.

The thymus tissue is then sliced thinly and
cultured, and tested for any abnormalities or diseases. After preparing
the tissue, surgeons implant the slices of thymus tissue into the
quadriceps muscles of both legs of the complete DiGeorge Syndrome baby.

Without
an immune system, the body cannot reject new organs. Therefore,
matching the donor thymus tissue to the complete DiGeorge Syndrome baby
is not necessary.

"We often find that parents, upon learning that
they can help provide a second chance for another sick child, are
delighted to donate tissue that otherwise would be discarded," said
Markert.

In treating babies with complete DiGeorge Syndrome, the
Duke physicians aim to complete the thymus transplant as soon as
possible after diagnosis. The children in the current study ranged in
age from 33 days to 133 days at the time of transplantation. The babies
are kept in isolation before and for several months after
transplantation to prevent infection. Such isolation is necessary
because the immune system will not develop until approximately five
months after transplantation.

"We monitor the children quite
intensively during the first year after transplantation," said Markert.
"We run several types of tests that can tell us whether the child's
body is forming immune cells and whether those cells are able to
respond to potential infections in the body."

One year after
transplantation, the surviving seven patients had T cell counts ranging
from 479 per cubic millimeter of blood to 1,580 per cubic millimeter.
"A normal infant can expect to have a T cell count of over 1,500 per
cubic millimeter," said Markert. "We're continuing to follow all of
these patients to see how their T cell counts change as they grow and
develop, but it is very encouraging to note that these children have
suffered very few infections or other immune-related disorders since
their immune systems began to take hold."

According to the
researchers, the survival rate and immunity levels in the children
treated at Duke suggest that thymus transplantation should be
considered as a standard treatment for immune deficiency in children
with complete DiGeorge Syndrome. "There are other types of experimental
treatments for complete DiGeorge Syndrome," said Markert, "however, the
results we're reporting are better than with any other therapy and are
the best one would expect given the heart and other congenital problems
in these infants."

The study was supported by grants from the
National Institutes of Health and the American Association of Allergy,
Asthma and Immunology Women Physicians in Allergy Award.

Joining
Markert in the study were Duke colleagues Marcella Sarzotti, Ph.D.;
Daniel Ozaki; Gregory Sempowski, Ph.D.; Maria Rhein; Laura Hale, M.D.;
Marilyn Alexieff; Jie Li; Elizabeth Hauser, Ph.D.; Barton Haynes, M.D.;
Henry Rice, M.D.; Michael Skinner, M.D.; Samuel Mahaffey, M.D., and
James Jaggers, M.D., as well as Leonard Stein , M.D., and Michael Mill,
M.D., of the University of North Carolina and Francoise Le Deist, M.D.,
of Laboratoire d'Immunologie Pédiatrique, Hôpital Necker–Enfants
Malades, Paris, France.

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