Severe Combined Immunodeficiency
Definition
Severe combined
immunodeficiency (SCID) is the most serious human immunodeficiency disorder(s). It is a group of congenital disorders in which both the humoral part of the patient's immune system and the cells involved in immune responses fail to work properly. Children with SCID are vulnerable to recurrent severe infections, retarded growth, and early
death.
Description
SCID is thought to affect between one in every 100,000 persons, and one in every 500,000 infants. Several different immune system disorders are currently grouped under SCID:
- Swiss-type agammaglobulinemia. This was the first type of SCID discovered, in Switzerland in the 1950s.
- Adenosine deaminase deficiency (ADA). About 50% of SCID cases are of this type. ADA deficiency leads to low levels of B and T cells in the child's immune system.
- Autosomal recessive. About 40% of SCID cases are inherited from the parents in an autosomal recessive pattern.
- Bare lymphocyte syndrome. In this form of SCID, the white blood cells (lymphocytes) in the baby's blood are missing certain proteins. Without these proteins, the lymphocytes cannot activate the T cells in the immune system.
- SCID with leukopenia. Children with this form of SCID are lacking a type of white blood cell called a granulocyte.
In order to understand why SCID is considered the most severe immunodeficiency disorder, it is helpful to have an outline of the parts of the human immune system. It has three parts: cellular, humoral, and nonspecific. The cellular and humoral parts of the system are both needed to fight infections-they recognize disease agents and attack them. The cellular system is composed of many classes of T-lymphocytes (white blood cells that detect foreign invaders called antigens). The humoral system is made up of B cells, which are the only cells in the body that make antibodies. In SCID, neither the cellular nor the humoral part of the immune system is working properly.
Causes and symptoms
SCID is an inherited disorder. There are two ways in which a developing fetus' immune system can fail to develop normally. In the first type of genetic problem, both B and T cells are defective. In the second type, only the T cells are abnormal, but their defect affects the functioning of the B cells.
For the first few months of life, a child with SCID is protected by antibodies in the mother's blood. As early as three months of age, however, the SCID child begins to suffer from mouth infections (thrush), chronic
diarrhea, otitis media and pulmonary infections, including pneumocystis pneumonia. The child loses weight, becomes very weak, and eventually dies from an opportunistic infection.
Diagnosis
SCID is diagnosed by the typing of T and B cells in the child's blood. B cells can be detected by immunofluorescence tests for surface markers (unique proteins)on the cells. T cells can be identified in tissue sections (samples) using enzyme-labeled antibodies.
Treatment
Patients with SCID can be treated with
antibiotics and immune serum to protect them from infections, but these treatments cannot cure the disorder. Bone marrow transplants are currently regarded as one of the few effective standard treatments for SCID.
Investigational treatments
In 1990, the Food and Drug Administration (FDA) approved PEG-ADA, an orphan drug (not available in US but available elsewhere), for the treatment of SCID. PEG-ADA, which is also called pegademase bovine, works by replacing the ADA deficiency in children with this form of SCID. Children who receive weekly injections of PEG-ADA appear to have normal immune functions restored. Another treatment that is still in the experimental stage is
gene therapy. In gene therapy, the children receive periodic infusions of their own T cells corrected with a gene for ADA that has been implanted in an activated virus.
Prognosis
Currently, there is no cure for SCID. Most untreated patients die before age two.
Prevention
Resources
Organizations
Immune Deficiency Foundation. 25 W. Chesapeake Ave., Suite 206, Towson, MD 21204. (800) 296-4433. http://www.primaryimmune.org.
National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-8923. (800) 999-6673. http://www.rarediseases.org.
Key terms
Adenosine deaminase (ADA) — An enzyme that is lacking in a specific type of SCID. Children with an ADA deficiency have low levels of both B and T cells.
Antigens — A substance that usually causes the formation of an antibody. A foreign invaders in the body.
B cell — A type of lymphocyte or white blood cell that is derived from precursor cells in the bone marrow.
Congenital — Present at the time of birth. Most forms of SCID are hereditary as well as congenital.
Gene therapy — An experimental treatment for SCID that consists of implanting a gene for ADA into an activated virus and merging it with some of the patient's own T cells. The corrected T cells are infused back into the patient every few months.
Humoral — Pertaining to or derived from a body fluid. The humoral part of the immune system includes antibodies and immunoglobulins in blood serum.
Lymphocyte — A type of white blood cell that is important in the formation of antibodies.
Orphan drug — A drug that is known to be useful in treatment but lacks sufficient funding for further research and development.
PEG-ADA — An orphan drug that is useful in treating SCID related to ADA deficiency.
T cells — Lymphocytes that originate in the thymus gland. T cells regulate the immune system's response to infections. The thymus gland is small or underdeveloped in children with SCID.
Thrush — A disease of the mouth caused by a yeast,
Candida albicans.
Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.
immunodeficiency
[im″u-no-de-fish´en-se] a deficiency of
immune response or a disorder characterized by deficient immune response; classified as antibody (B cell), cellular (T cell), or combined deficiency disorders. Antibody immunodeficiencies are marked by hypo- or
dysgammaglobulinemia, recurrent bacterial otitis media, and sinopulmonary infections. Cellular immunodeficiencies are characterized by recurrent low-grade or
opportunistic infections, by
graft-versus-host disease or reaction after blood transfusions, and by severe disease after immunization with live vaccines. See also
acquired immunodeficiency syndrome.
common variable immunodeficiency (CVID) a heterogeneous group of disorders characterized by
hypogammaglobulinemia, decreased antibody production in response to antigenic challenge, and recurrent pyogenic infections, often associated with hematologic and autoimmune disorders. Most patients have normal numbers of circulating B
cells but lack plasma
cells and appear to have an intrinsic defect of B cell differentiation. However, two other forms are also recognized: that due to a disorder of
T lymphocyte regulation and that due to production of autoantibodies against T and B lymphocytes.
severe combined immunodeficiency (SCID) any of several rare congenital diseases, some of autosomal recessive and some of X-linked inheritance, in which both humoral and cell-mediated
immunity fail to develop normally and
T lymphocytes are absent or nearly so. In some forms,
B lymphocytes are also absent. Early diagnosis is essential to prevent
opportunistic infections. Persistent
diarrhea,
chronic mucocutaneous candidiasis, and
failure to thrive may occur in infancy. Blood transfusions can result in
graft-versus-host disease and routine vaccinations in fatal infection. Unless immune function is restored by a matched-donor bone marrow or fetal tissue transplantation or the patient is kept in complete isolation, the prognosis is poor.
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.