Severe combined immune deficiency

Severe combined immune deficiency (SCID) is a rare inherited disorder in which multiple components of the immune system are affected. About 50% of SCID cases are caused byX-linked recessive mutations in the gene encoding a subunit of a receptor for interleukins 2,4,... 

Currently, more than 400 human somatic cell gene therapy protocols are being tested. Most of these involve the use of genetically modified cells to treat noninherited diseases. For example, normal copies of the p53 tumor suppressor gene are inserted into lung tumors to halt tumor progression, and genetically modified cells have been used to create new coronary vessels in patients with coronary heart disease. Success has also been achieved in the treatment of hereditary disease (most notably, the recent successful treatment of X-linked severe combined immune deficiency see Clinical Correlate). 

In 2000, French researchers announced the first gene therapy cure in nine children with X-linked severe combined immune deficiency (X-SCID). This rare condition is caused by the inherited loss of a protein that is part of the docking site for critical immune system signal proteins. Because of this defect, children with X-SCID have no mature, working lymphocytes—critical immune system cells. 

X-linked severe combined immune deficiency (X-SCID)— Absence of a functioning immune system inherited with the X chromosome. X-linked refers to inheritance with the X chromosome, one of the chromosomes involved in determining gender. In humans, women have two X chromosomes, and men have an X and a Y chromosome. X-linked genes can only be inherited by a boy from his mother, since his father would have given him his Y chromosome. 

NOD-SCID non-obese diabetic severe combined immune deficiency... 

Cavazzana-Calvo, M. (2000). Gene therapy of human severe combined immune deficiency (SCID)-Xl disease. Science, 288, 669-672. 

Successful peripheral T-lymphocyte-directed gene transfer for apatient with severe combined immune deficiency caused by adenosine deaminase deficiency. Onodera, M., Ariga, T., Kawamura, N., Kobayashi, I., Ohtsu, M., Yamada, M., Tame, A., Furuta, H., Okano, M., Matsumoto, S., Kotani, H. et al. (1998). Blood, 91 (1) 30-36. 

T-lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase. Weinberg, K., Hershfield, M.S., Bastian, J., Kohn, D., Sender, L., Parkman, R., Lenarsky, C. (1993).JClin Invest, 2 596-602. 

Mosier, D. E., Baird, S. M. and Kirven, M. B. (1990). EBV-associated B-cell lymphomas following transfer of human peripheral blood lymphocytes to mice with severe combined immune deficiency. Curr. Top. Microbiol. Immunol. 166 317-323. 

Severe combined immune deficiency (SCID) Adenosine deaminase... 

Severe Combined Immune Deficient Mouse Model... 

Murphy, W., Taub, D., Anver, M., Conlon, K., Oppenheim, J., Kelvin, D. and Longo, D. (1994). Human RANTES induces the migration of human T lymphocytes into the peripheral tissues of mice with severe combined immune deficiency. Eur. J. Immunol. 24, 1823-1827. 

Barry TS, Haynes BF. In vivo models of human lymphopoiesis and autoimmunity in severe combined immune deficient mice. J Clin Immunol 1992 12(5) 311-324. 

Persons with severe combined immune deficiency (SCID) are totally unable to mount an immune response to antigens. Both the B and T lymphocytes are affected. The disease arises from an inherited lack of a degradative enzyme, adenosine deaminase (ADA). The reaction shown here illustrates the pathways affected. Lack of ADA allows deoxyadenosine triphophosphate (dATP) to accumulate from the degradation of DNA. High dATP levels inhibit production of the other dNTPs needed for DNA replication because of their allosteric effects on the enzyme ribonucleotide reductase. 

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