Granulomatous Disease (CGD)
The most common white
blood cells -- neutrophils -- combat infections by producing germ-killing
substances: hydrogen peroxide and bleach. People with CGD have genetic
mutations that prevent the blood cells from making the proteins necessary
for this process. As a result, infections that most of us easily fight
are life-threatening to people with CGD.
|Two-thirds of people with CGD are
males who inherited
the disease on the X-chromosome
from their mother (males have an X-chromosome from their mother and
from their father). In these cases, CGD is called an X-linked genetic
disease. In general, females do not have problems when one of their
X-chromosomes carries the X-linked
CGD mutation. Non-X-linked forms of CGD affect both boys and girls.
From gene to protein
In 1985, Dr. Uta Francke
at Yale University and her colleagues described a man with X-linked CGD
who also had three other X-linked diseases. When his X-chromosome was
examined, there was a small piece missing, indicating where on the X-chromosome
all four of these disease-linked genes could be found.
In 1987, Dr. Stuart Orkin
in the Howard Hughes Medical Institute at Harvard University and his colleagues
used this information to isolate the X-linked CGD gene. Since then, three
other CGD genes have been found on other chromosomes,
making CGD four distinct genetic disorders.
Daily doses of antibiotics
reduce infections in people with CGD. Injections of interferon gamma,
a potent immune system hormone, also reduce infections in these patients.
Scientists used recombinant
DNA technology to make useful amounts of this hormone from bacteria.
While these treatments are not a cure for CGD, they have improved the
outlook for people with CGD.
|A gene therapy trial to treat a non-X-linked
form of CGD started at NIH in July 1995. Immature white blood cells
were purified from the blood of a person with CGD. The cells were
treated with the normal gene, and put back into the same person. Five
people with CGD were treated this way. Although only some corrected
cells stayed in the bloodstream for several months, this effort represented
an important step in developing gene therapy for CGD. This photo shows
white blood cells from one of the people who received gene therapy.
The dark cell has been corrected by the gene treatment. For more on
gene therapy, see this page.
of NBT test.
Courtesy of Dr. Harry L. Malech and Dr. Douglas Kuhns, National Institute
of Allergy & Infectious Diseases