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Severe combined immunodeficiency

Image:Mergefrom.gifIt has been suggested that X-linked severe combined immunodeficiency be mergedinto this article or section. ([[{{{2|: talk:Severe_combined_immunodeficiency}}}|Discuss]])

**{{{Name|Severe combined immunodeficiency}}}**
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ICD-10	D81.0-2
ICD-O:	{{{ICDO}}}
ICD-9	279.2
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Severe Combined Immunodeficiency, or SCID, is a genetic disorder in which both "arms" (B cellsand T cells) of the adaptive immune system are crippled, due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency. It is also known as the "bubble boy" disease because its victims are extremely vulnerable to infectious diseases and must live (if untreated) in a completely sterile environment. The most famous case is the boy David Vetter.

SCID affects about 1 in 80,000 live births. These babies, if untreated, usually die within 1 year due to severe, recurrent infections. Chronic diarrhea, ear infections, recurrent Pneumocystis jirovecipneumonia, and profuse oral candidiasiscommonly occur. Treatmentoptions are much improved since David Vetter, and living in a bubble is no longer necessary.

Inhaltsverzeichnis

1 Types
- 1.1 IL-7 signalling pathway
- 1.2 VDJ recombination
- 1.3 Adenosine deaminase
2 Detection
3 Treatment
4 External links

Types

IL-7 signalling pathway

Most cases of SCID are derived from mutationsin the γ_c chain in the receptors for interleukinsIL-2, IL-4, IL-7, IL-9 and IL-15. These interleukins and their receptors are involved in the development and differentiation of T and B cells. Deleterious mutations in the gamma-chain or in the JAK3 protein cause a form of SCID that is characterized by low numbers of T and NK cells, and presence of non-functional B cells.

The IL-2 receptor γ (IL-2Rγ) geneis located on the X chromosomeand mutation of this gene causes X-linked SCID.

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

VDJ recombination

The manufacture of immunoglobulinsrequires recombinase enzymes derived from the recombination activating genes RAG-1 and RAG-2. These enzymes are involved in the first stage of VDJ recombination, the process by which segements of a B cellor 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 VDJ 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. Lack of ADA causes accumulation of dGTP. This metabolite is toxic to lymphoid stem cells.

Detection

Standard testing of SCID is not performed for newborns due to the rarity of the disease and the cost of the testing. SCID can be detected by sequencing fetal DNA if a known history of the disease exists. Otherwise, SCID is not detected until about six months of age, usually indicated by recurrent infections. The delay in detection is due to the fact that newborns carry their mother's antibodiesfor the first few weeks of life and have not yet been exposed to any diseases.

Treatment

The most common treatment for SCID is bone marrow transplantation, which requires matched donors (a sibling is generally best). David Vetter, the original "bubble boy," endured several failed transplantations, and finally passed away because of an unscreened virus, Epstein-Barr, in his newly-transplanted bone marrow from his sister. Today, transplants done in the first three months of life have a high success rate.

More recently, gene therapyhas proved useful. Transductionof the missing gene to hematopoietic stem cells using viralvectorsis 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. These trials were stopped when it was discovered that three of eleven patients in one trial had developed leukemiaresulting from the insertion of the gene-carrying retrovirus near an oncogene. Work is now focusing on correcting the gene without triggering an oncogene. No leukemia cases have yet been seen in trials of ADA-SCID, which does not involve the gamma c gene which may be oncogenic when expressed by a retrovirus.

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.

External links

scid.netSCID self-help support group and resource guide
Learning About Severe Combined Immunodeficiency (SCID)NIHde:SCID

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Retrieved from "http://en.wikipedia.org/Severe_combined_immunodeficiency"

Categories: Articles to be merged| Rare diseases| Immunology| Immune system disorders

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Severe+combined+immunodeficiency Wikipedia article Severe combined immunodeficiency.

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