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NIAID
CEDS
What Is CEDS?
CEDS is a very rare genetic disorder
of the immune system. CEDS stands
for “caspase eight deficiency state.”
The disorder is characterized by an
enlarged spleen and lymph nodes,
recurrent sinus and lung infections,
recurrent viral infections, and a low
level of infection-fighting antibodies.
CEDS is diagnosed based on clinical
and laboratory findings as well as Genetics primer: All the cells in the body contain instructions on how to do
their job. These instructions are packaged into chromosomes, each of which
genetic testing. contains many genes, which are made up of DNA. Errors, or mutations, in the
genes can cause diseases such as CEDS. Credit: NIAID

Genetics
CEDS is caused by mutations in the CASP8 gene, which
provides instructions for production of the protein
caspase eight, which is also abbreviated as CASP8. The
CASP8 protein is involved in programmed cell death,
or apoptosis. The body must maintain a careful balance
between proliferation of immune cells and apoptosis
to defend against pathogens and avoid autoimmunity.
The mutations that cause CEDS destabilize the CASP8
protein and block its function, leading to buildup of
immune cells.

Inheritance
CEDS is inherited in an autosomal recessive manner.
This means that affected people have a mutation on each
In this example, two unaffected parents each
of their two copies of CASP8—one inherited from their carry one copy of a gene mutation for an
mother and one from their father. Sometimes the two autosomal recessive disorder. They have one
affected child and three unaffected children, two
copies have mutations that are identical, or homozygous. of which carry one copy of the gene mutation.
This often involves parents who are related to each other. Credit: U.S. National Library of Medicine

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health
National Institute of Allergy and Infectious Diseases
Alternatively, the mutations in each copy of the CASP8 gene are different. These are called compound
heterozygous mutations.

In either case, parents of a child with CEDS are usually “carriers,” meaning they have one mutated
copy of CASP8 and one normal copy. Carriers typically do not experience any symptoms of CEDS
and lack immune-function abnormalities.

Clinical Symptoms
CEDS is related to autoimmune lymphoproliferative syndrome and used to be called ALPS type IIB.
Although CEDS and ALPS share problems with apoptosis, CEDS is different from ALPS because
of its additional immune deficiency symptoms. The symptoms of CEDS include splenomegaly
(an enlarged spleen), lymphadenopathy (enlarged lymph nodes), recurrent sinopulmonary (sinus
and lung) infections, recurrent mucocutaneous herpesvirus infections, persistent warts, molluscum
contagiosum, and hypogammaglobulinemia (low antibody levels). Although immune cells called
lymphocytes sometimes infiltrate certain organs, such as the lungs, liver, and kidneys, autoimmune
problems are minimal. Lymphoma, a type of cancer, has not been observed in CEDS patients.
However, people with ALPS are at increased risk of developing lymphoma.

Laboratory Findings
Doctors may perform immunologic studies to look for features that suggest CEDS. For example, they
may assess serum immunoglobulin, or antibody, levels; antibody function; and lymphocyte activation.
Patients with CEDS have hypogammaglobulinemia and develop poor antibody responses to certain
vaccines. In addition, their immune cells, including B cells, T cells, and NK cells, do not activate
well in response to stimuli.

Prognosis and Treatment

Given the rarity of CEDS, the prognosis for and optimal treatment of people with this condition
remain unclear. People with CEDS have done well while taking intravenous immunoglobulin and
prophylactic acyclovir, an antiviral drug, to prevent sinopulmonary infections and mucocutaneous
herpesvirus outbreaks. Investigators at the National Institute of Allergy and Infectious Diseases, part
of the National Institutes of Health, are conducting clinical studies to identify new approaches for
the diagnosis and treatment of this disorder. More information can be found on clinicaltrials.gov,
using the study identifiers NCT00246857 and NCT00001467.

CEDS and Your Family

Living with CEDS can be difficult not only for the person who has it but for their family members
as well. It is important for families to talk openly about CEDS and about how the family is dealing
with it so misconceptions can be corrected and children can learn to cope with their reactions.
Some children with CEDS have to work hard to develop their self-confidence and sense of security.

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Everyone benefits from being reminded that they have many positive characteristics, but this
is especially important when a child’s appearance attracts attention (for example, due to large
lymph nodes).

Some children who have siblings with the disease feel anxious about their brother or sister being in
pain or even dying from the disease. Some think that they may develop symptoms because they look
or act like a sibling who has the disease or that the disease is contagious. Some children struggle with
how much time their parents spend with their sick sibling. Many families benefit from meeting or
talking to other families affected by the same rare disease. Patient organizations such as the Immune
Deficiency Foundation (www.primaryimmune.org) are also great resources for providing useful
information and support. Counseling can also help families cope with the challenges of CEDS.

At the same time, many families say that the disease has brought them closer together. Through
their experiences with the disease and its treatment, family members learn about controllable and
uncontrollable aspects of life. Although certain aspects of the disease cannot be controlled, how a
family responds to the stress of any illness is controllable and an important aspect of managing CEDS.
Children also learn who they can turn to for support and how to solve problems. Acknowledging
both the challenges and opportunities that CEDS presents helps children develop resilience.

NIAID

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Glossary
Apoptosis—Programmed cell death, an important part of a Lymphadenopathy—Enlarged lymph nodes.
healthy immune system. Lymphocytes—A class of white blood cells that are part of the
Autoimmunity—A process during which a person’s immune immune system.
system attacks healthy cells, organs, and tissues. Lymphoma—A type of cancer that occurs when certain immune
B cells—Immune cells that present antigens to T cells and cells start dividing uncontrollably and no longer behave like
produce antibodies, or immunoglobulins. normal immune cells.
Cell—The basic unit of living organisms. Human cells consist of Molluscum contagiosum—A viral skin infection that results in
a nucleus (control center) and cellular organs, called organelles, round, firm, painless bumps.
enclosed by a membrane. Groups of cells with similar structure Mucocutaneous herpesvirus—An infection of the skin or mucus
and function form tissues. membranes (mouth, nose, eyes, genitals) with herpesvirus.
Chromosome—A thread-like structure made up of DNA that is Mutation—A change in the DNA sequence that is associated
tightly coiled around supporting proteins. Chromosomes reside with disease or susceptibility to disease.
in the control center, or nucleus, of a cell.
NK cells—Small lymphocytes that are part of the first line of
DNA (deoxyribonucleic acid)—A self-replicating material immune defense.
present in nearly all living organisms. It is the carrier of genetic
information. Phenotype—A person’s observable characteristics.

Gene—A unit of heredity that is transferred from parent to child. Proliferation—The rapid reproduction of cells.
Genes are made up of DNA. Sinopulmonary infections—Infections of the sinuses and/or
Hypogammaglobulinemia—A type of immune deficiency that lungs.
is characterized by a reduction in all types of gamma globulins, Splenomegaly—Enlarged spleen.
or infection-fighting antibodies.
T cells—Lymphocytes produced or processed by the thymus
Immune system—A system of biological structures and processes (a small organ located in the upper chest under the breastbone)
within the body that protects it against “foreign” threats such as that are actively involved in the immune response.
bacteria or viruses.

NIAID

July 2015
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