Newborn Testing for Immune Disorders Could Save Lives
date : 4/21/2004
media contact : Becky Oskin , 919-684-4966 or 919-684-4148
becky.oskin@duke.edu
DURHAM, N.C. -- A simple, inexpensive blood test performed
at birth to screen for immune disorders could dramatically
increase the chance of survival for babies born with such
potentially fatal disorders as severe combined immunodeficiency
disease (SCID).
Physicians at Duke University Medical Center have performed
stem cell transplants in 136 infants with SCID in the
past 22 years. The survival rate for 38 infants receiving
transplants in the first 3.5 months of life is 97 percent,
but the rate drops to 69 percent for infants who were
transplanted after that age, Rebecca Buckley, M.D., reports
in the April 23, 2004, Annual Review of Immunology.
The main cause for the drop in survival rate is serious
infections SCID babies develop in the first few months
of life. Infants with SCID have little or no immune system.
Without treatment, they die of infection before their
first or second birthdays. But for infants without a known
family history of SCID, the average age of referral for
immune testing is approximately 6 months, Buckley said.
"The tragedy is that most patients are critically
ill by then,'' she said.
Buckley believes that all newborns should be screened
for immune deficiency disorders at birth. "SCID is
a pediatric emergency. There is no screening for any primary
immunodeficiency disease at birth or during childhood and
adulthood in any country. Thus, most patients are not diagnosed
until they develop a serious infection, which certainly
adversely affects the outcome of therapy," said Buckley,
a professor in Duke's division of pediatric allergy and
immunology.
Early treatment also reduces costs -- a transplant in
the first three months of life can cost less than $50,000,
but the cost of care skyrockets up to millions of dollars
for seriously ill patients, with less guarantee of success.
And SCID patients who received stem cell transplants from
related donors within the first 28 days of life developed
a more robust immune system, with higher levels of T cell
reconstitution and output from the thymus gland. T cells
are white blood cells that are essential for normal function
of the immune system, Buckley reports.
Nearly all SCID cases can be diagnosed at birth by counting
the number of lymphocytes, a type of white blood cell,
present in umbilical cord blood, Buckley said. Infants
with SCID have a profound deficiency of lymphocytes, due
to the deficiency of T cells that help fight infections.
Children with other immune disorders could also be identified
through this test, which costs an average of $50 at a
commercial laboratory. Researchers at the National Humane
Genome Research Institute are developing a test for immunodeficiency
disorders that could be performed on the small blood sample
now taken from newborns to screen for certain metabolic
disorders.
Nine forms of SCID have been identified in the past 10
years, caused by mutations of single genes. However, Buckley
has treated 30 patients without mutations in the known
SCID genes, making it likely other causes are yet to be
discovered. The most common form of SCID is X-linked recessive,
a mutation inherited on the X chromosome. Because X-linked
recessive genes are expressed in girls only if a child
receives two copies of the gene -- one from each parent
-- the disease is more common in boys, who only need one
copy for an X-linked recessive gene to be expressed. SCID-X1
accounts for 46 percent of U.S. cases.
The incidence of SCID has been projected to range from
one in every 100,000 to 500,000 births -- more frequent
than disorders such as Huntington's disease. "However,
no one truly knows how common this disease is. I suspect
that it is much more common than thought because a lot
of SCID patients probably die before their disease is
recognized," Buckley said.
Buckley and her colleagues at Duke University Medical
Center treat SCID patients via stem cell transplants derived
from donor bone marrow, typically from a parent or matched
sibling. Transplant recipients do not need pretransplant
chemotherapy or prophylactic treatment for graft-versus-host
disease. Infants with SCID have a complete absence of
T cell function, so they cannot reject the transplants.
The bone marrow is processed to remove T cells, preventing
the donor T cells from attacking the recipient, known
as graft-versus-host disease. Mature, donor-derived, T
cells typically appear in SCID patients within 90 to 120
days after transplant. The success of treatment varies
among different forms of SCID.
Clinicians are striving to improve the success of transplant
therapy and create more robust immune systems by giving
higher numbers of stem cells in preparations nearly devoid
of T cells, Buckley added. "If the imperfect results
seen with stem cell therapy in the past were due to an
insufficient number of stem cells, this approach should
result in better immune reconstitution. The only remaining
obstacle would then be to ensure diagnosis is made early
before untreatable infections develop," she said.
Of the 136 SCID patients treated at Duke, 105 (77 percent)
are alive. None show any evidence of susceptibility to
opportunistic infections and most are in good general
health. The oldest is 22 years of age. All 15 recipients
of marrow from perfectly matched donors and 89 of the
121 recipients of T cell-depleted marrow from related
donors are among the survivors.
Of the 38 infants transplanted during the first 3.5 months
of life, 37 (97 percent) survive, compared to 68 survivors
among the 98 transplanted after that age (69 percent success).
Twenty-four of the 31 deaths occurred from viral infections.
Graft-versus-host-disease (GVHD) occurred in 40 of the
121 patients given T cell-depleted parental bone marrow,
but most of the GVHD was mild and required no treatment;
there were no deaths from GVHD. In 35 of 40 GVHD cases,
the complication occurred when there was persistence of
transplacentally transferred maternal T cells.
Original Article can be found at DukeMedNews.org
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