Lack of CD70, a protein found on the surface of
several types of immune cells, leads to immune problems. No specific treatment for CD70
deficiency currently exists.
Investigators at the National Institutes of Health (NIH) and
international colleagues have identified that this genetic immune disorder is
characterized by increased susceptibility and poor immune control of
Epstein-Barr virus (EBV) and, in some cases, an EBV-associated cancer
called Hodgkin's lymphoma.
‘Lack of CD70 protein has been characterized by increased susceptibility and poor immune control of Epstein-Barr virus (EBV) and, in some cases, an EBV-associated cancer called Hodgkin's lymphoma.’
The researchers studied two unrelated sets of
siblings with similar immune problems and determined their symptoms
were likely caused by a lack of CD70. Scientists at the National Institute of
Allergy and Infectious Diseases (NIAID), part of NIH, conducted the
research with an international team of collaborators.
Both sets of siblings had evidence of uncontrolled infection with
EBV, a common and usually mild virus, which resulted in the development
of Hodgkin's lymphoma in three of these children. Each child also had
other immune symptoms, such as reduced activity of pathogen-fighting T cells, low production of antibodies and poor activation of antibody-producing B cells.
The researchers analyzed the genomes of all four children and found that each had two mutated copies of the CD70
gene, resulting in nonfunctioning or nonexistent CD70 proteins. All
four parents, who had healthy immune systems, had only one copy of the
mutation - indicating that CD70 deficiency follows an autosomal recessive pattern of inheritance.
This means affected individuals receive a flawed gene from each parent
in order to have symptoms. Each of the four children has recovered
from Hodgkin's lymphoma and is receiving antibody infusions to help
bolster the immune system.
This work also offers insight into the normal role of CD70. Previous
studies showed that CD70 interacts with another immune cell protein
called CD27, an interaction that may be important for the proper
function of lymphocytes. This hypothesis is affirmed by these latest
findings on CD70 deficiency.
The research also indicated that
investigators testing experimental medications that decrease the
activity of CD70 or CD27 - a possible strategy for combating autoimmune
disease - should be aware of a possible risk of EBV-related