severe combined immunodeficiency (SCI) - Types, Detection, Treatment

A type of immune deficiency resulting from failure of the thymus to develop, and thus to produce lymphocytes, key cells in the body's immune response. Babies born with this condition have little ability to withstand infection, and rarely survive beyond infancy; but some success has been obtained with thymic transplantation.

Severe combined immunodeficiency
Classifications and external resources

ICD-10	D81.0-2
ICD-9	279.2

Severe Combined Immunodeficiency, or SCID, is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes.

SCID affects about 1 in 100,000 live births.

Types

JAK3

Janus kinase-3 (JAK3) is an enzyme that mediates transduction downstream of the γc signal. Mutation of its gene also causes SCID.

V(D)J recombination

The manufacture of immunoglobulins requires recombinase enzymes derived from the recombination activating genes RAG-1 and RAG-2. These enzymes are involved in the first stage of V(D)J recombination, the process by which segements of a B cell or T cell's DNA are rearranged to create a new T cell receptor or B cell receptor (and, in the B cell's case, the template for antibodies). Certain mutations of the RAG-1 or RAG-2 genes prevent V(D)J recombination, causing SCID.

Adenosine deaminase

Another well-known form of SCID is caused by a defective enzyme, adenosine deaminase (ADA), necessary for the breakdown of purines.

Detection

Standard testing of SCID is not performed for newborns due to the rarity of the disease and the cost of the testing. Otherwise, SCID is not detected until about six months of age, usually indicated by recurrent infections.

Treatment

The most common treatment for SCID is bone marrow transplantation, which requires matched donors (a sibling is generally best).

More recently, gene therapy has proved useful. Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. The first gene therapy trials were performed in 1990, with peripheral T cells. In 2000, the first gene therapy "success" resulted in SCID patients with a functional immune system.

Trial treatments of SCID have been gene therapy's only success; since 1999, gene therapy has restored the immune systems of at least 17 children with two forms (ADA-SCID and X-SCID) of the disorder.