Severe combined immune deficiency SCID

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,... 

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

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

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. 

Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O Shea JJ, et al Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 1995 377 65-68. 

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... 

Gansbacher B (2003). Report of a second serious adverse event in a clinical trial of gene therapy for X-linked severe combined immune deficiency (X-SCID). Position of the European Society of Gene Therapy (ESGT). /. Gene Med. 5 261-262. 

Low levels or absence of adenosine deaminase (ADA) is associated with one form of severe combined immunodeficiency disease (SCID) characterized by B-andT-lymphocyte dysfunction due to toxic effects of deoxyadenosine (HI9). Most patients present as infants with failure to thrive, repeated infections, severe lymphopenia, and defective cellular and humoral immunity. Disease severity is correlated with the degree of deoxyadenosine nucleotide pool expansion and inactivation of S-adenosylhomocysteine hydrolase in red blood cells. Up to now, more than 40 mutations have been identified (A4, H20, S5, S6). The majority of the basic molecular defects underlying ADA deficiency of all clinical phenotypes are missense mutations. Nonsense mutations, deletions ranging from very large to single nucleotides, and splicing mutations have also been reported. It is likely that severe... 

As is implied by its name, the first TNF-a-dependent mechanism described was the induction of tumor necrosis in vivo through its role in tumor vasculature. However the mechanisms of the in vitro toxicity of TNF-a to tumor cells imply apoptosis rather than necrosis [97], Tumor necrosis in SCID (severe combined immuno-deficiency) mice treated with LPS does not lead to the rejection of tumors [98], Furthermore, necrosis and tumor regression must be dissociated since anti-IFN-y antibodies inhibit LPS-induced regression of Meth A sarcoma in mice, but not the necrotic hemorrhage attributed to TNF-a. It is now accepted that the antitumoral effect of TNF-a is indirect and dependent on acquired immune response. Matsumoto et al. [99] reported that, while TNF-a itself has no effect on hepatoma KDH-8 tumor cells in vitro, the antitumoral effect of the lipid A ONO-4007 against KDH-8 tumors in vivo is inhibited by anti-TNF-a antibodies in WKAH rat, showing an indirect effect of TNF-a. 

Pegademase (adenosine deaminase EC 3.5.4.4) is a PEGylated enzyme used for treating patients with adenosine deaminase (ADA) deficiency [76] and suffering from a form of severe combined immunodeficiency syndrome (SCID), a disease that occurs in about 1/50,000 births. SCID patients have a severely crippled immune system and cannot clear or recover from the mildest microbial or viral infections. 

The answer is D. Impaired immune function in severe combined immunodeficiency (SCID) is the direct result of blocked DNA synthesis due to inadequate supplies of de-oxyribonucleotides in B and T cells. This effect arises by dATP-induced allosteric inhibition of ribonucleotide reductase, which catalyzes reduction of the 2 -hydroxyl groups on ADP and GDP to form dADP and dCDP. The ultimate cause of many cases of SCID is adenosine deaminase deficiency, which leads to accumulation of dATP and consequent inhibition of ribonucleotide reductase. Although the other enzymes mentioned are also involved in purine nucleotide metabolism, their deficiencies do not lead to SCID. 

Patients with ADA deficiency lack both T- and B-lymphocyte-mediated functions, namely, cellular and humoral immunity, respectively, and exhibit a severe combined immunodeficiency (SCID) disorder. Other genetic defects can cause SCID (Chapter 35), but ADA deficiency is responsible for about one-third of patients who have SCID. PNP deficiency is associated only with T-lymphocyte dysfunction. 

A deficiency in adenosine deaminase activity is associated with some forms of severe combined immunodeficiency (8CTD), an immunological disorder. Persons with the disorder have severe recurring infections, often leading to death at an early age. SCID is characterized by a loss of T cells, are crucial to the immune response (Section 33.5), Although the biochemical basis of the disorder is not clearly established, a lack of adenosine... 

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