Disease relevance of Severe Combined Immunodeficiency

• Thus selected specimens of advanced human prostate cancer can be propagated in SCID mice in a manner that recapitulates the clinical transition from androgen-sensitive to androgen-independent growth, accompanied by micrometastasis [1].
• Both SCID and SCID-BL lymphomas are phenotypically CD4-8+ and/or CD4+8+, but only the SCID-BL tumors express CD3 [2].
• Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice [3].
• We conclude that the SCID mouse serves as a versatile in vivo model that allows the study of P. falciparum-infected erythrocyte adhesion as it occurs in human cerebral malaria [4].
• Transfer of these pre-B cell lines into SCID mice leads to hypergammaglobulinemia of IgM (600-900 micrograms/ml), IgG2a (1-3 mg/ml), and IgG3 (300-500 micrograms/ml) for the next 3-5 mo [5].

Psychiatry related information on Severe Combined Immunodeficiency

• In total, 75% of the patients fulfilled the criteria for a personality disorder according to the SCID Screen questionnaire, mostly (55%) within cluster C [6].
• In the subsample of patients who had COPD and received a diagnosis using the SCID, 65% received an anxiety and/or depressive disorder diagnosis [7].
• Participants who had results positive for panic disorder completed the Panic Disorder Module of the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) by the research psychiatrist and the treating emergency physician, each blinded to the other's rating [8].
• METHOD: Seventy-four persons identified with a lifetime CIDI/DSM-III-R bipolar disorder and 40 persons with a major depressive disorder (MDD) were reinterviewed with the Structured Clinical Interview for DSM (SCID) [9].
• Three hundred seventy-five patients with major depressive disorder were evaluated for comorbid drug dependence using the Structured Clinical Interview for DSM-III-R (SCID) [10].

High impact information on Severe Combined Immunodeficiency

• Finally, a deficiency of CD45, a critical regulator of signaling thresholds in immune cells, also causes SCID [11].
• The bare lymphocyte syndrome and the regulation of MHC expression [12].
• Adenosine deaminase (ADA) deficiency causes a form of severe combined immunodeficiency [13].
• Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency [14].
• In XSCID and SCID resulting from mutations in JAK3, which encodes a Janus family tyrosine kinase that couples to gamma(c) and is required for gamma(c)-dependent signalling, T- and natural killer (NK)-cells are decreased but B-cell numbers are normal (T(-)B(+)NK(-)SCID) [15].

Chemical compound and disease context of Severe Combined Immunodeficiency

• We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol [16].
• IL-2R gamma is a common gamma chain, gamma c, also shared by the IL-7 (ref. 10) and IL-4 (refs 11, 12) receptors, which when mutated results in X-linked severe combined immunodeficiency [17].
• In SCID mice, in contrast, virulent mycobacteria grew rapidly and progressively in all organs, as did BCG, although at a slower rate [18].
• However, H37Ra failed to grow progressively in any organs of SCID mice, unless the mice were treated with hydrocortisone [18].
• We report here that spleens from SCID mice have undergone phenotypic expansion of cells bearing the NK-2 and asialo GM1 markers (70-80%) characteristic of NK cells and this expansion is accompanied by a 3-4-fold enrichment in NK cytolytic activity over their normal C.B-17 littermates [19].

Biological context of Severe Combined Immunodeficiency

• This study shows that complete inactivation of Prkdc in a novel insertional mouse mutant recapitulates the SCID phenotype and that Prkdc and scid are alleic [20].
• DNA-binding defects in the protein RFX5 cause bare lymphocyte syndrome or major histocompatibility antigen class II deficiency [21].
• Upon expression in 32Dcl3 growth factor-dependent myeloid precursor cells, STAT5 activation-deficient BCR/ABL SH3+SH2 domain mutants functioned as tyrosine kinase and activated Ras, but failed to protect from apoptosis induced by withdrawal of interleukin 3 and/or serum and did not induce leukemia in severe combined immunodeficiency mice [22].
• All CD3-responsive CD4+ T cell clones obtained from such lines were SCID mouse specific, recognizing native major histocompatibility complex class II products on the murine cells [23].
• Rather, virulence enhancement seemed to depend on inflammatory cells, since priming with trans-sialidase had no significant effect in severe combined immunodeficiency mice, which lack functional T and B lymphocytes [24].

Anatomical context of Severe Combined Immunodeficiency

• We have previously described a type of selective T cell deficiency (STD) characterized by persistent infections reminiscent of severe combined immunodeficiency [25].
• A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution [26].
• Three infants in two families with severe combined immunodeficiency were found to have no detectable erythrocyte adenosine deaminase [27].
• Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) - termed the SCID leukemia-initiating cell, or SL-IC - possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell [28].
• Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates [29].

Gene context of Severe Combined Immunodeficiency

• These results demonstrate that increased recombination activity after the loss of PARP anti-recombinogenic function can rescue V(D)J recombination in SCID mice and indicate that PARP and DNA-PK cooperate to minimize genomic damage caused by DNA strand breaks [30].
• Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency [15].
• In addition, CIITA fully corrects the MHC class II regulatory defect of cells from patients with bare lymphocyte syndrome [31].
• We used a mouse model of Jak3-deficient SCID to test a gene therapy approach for treatment of this disease [32].
• The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 were found to be critical for murine bone marrow engraftment by human severe combined immunodeficient (SCID) repopulating stem cells [33].

Analytical, diagnostic and therapeutic context of Severe Combined Immunodeficiency

• The effects of IDN-5109 and paclitaxel on tumor growth in vivo were studied with the use of tumors established through xenografts of Pgp-expressing SW-620 and DLD1 cells in severe combined immunodeficiency mice [34].
• Analysis of T cell receptor (TCR) V beta usage by reverse transcriptase polymerase chain reaction in the infiltrating MNC transferred into SCID mice revealed a marked skew towards the preferential use of certain V beta genes, which was not seen in the peripheral blood MNC, in only the positive group [35].
• In patients with severe combined immunodeficiency HLA-matched (n = 41) and T-cell-depleted HLA-mismatched BMT (n = 46) resulted in 68% and 57% disease-free survival, respectively; after HLA-mismatched transplants, older age (greater than 6 months) and adenosine-deaminase deficiency resulted in poorer survival [36].
• A number of new animal models, including the formation of liver abscesses in SCID mice and intestinal infection in human intestinal xenografts, have proven useful to confirm the critical role of cysteine proteinases in invasion [37].
• In both SCID and RAG-1-deficient recipients, aortic allografts showed a virtual absence of neointimal formation (%LR, 3.7 +/- 2.1 and 3.8 +/- 1.6 in SCID and RAG-1-deficient recipients, respectively), indicating a critical etiological role for alloimmune responses in this model [38].

References