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Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between a third and half of all males with SCID and no family history of immunodeficiency represent the first manifestation in their family of a new mutation of the gene that causes X-linked SCID. These patients, like boys with a positive family history of X-linked SCID, have markedly reduced numbers of T cells, elevated numbers of B cells, and hypogammaglobulinemia. The hypogammaglobulinemia is due, at least in part, to the expression of the gene defect in B cells as well as in T cells. Patients with X-linked SCID who are treated with bone marrow transplant tend to engraft T cells readily but they do not engraft B cells unless they are treated with cytoreductive therapy prior to transplant. B-cell function after transplant tends to be poor, even in patients who have received transplants from HLA matched siblings. Better transplant strategies are required to achieve optimum long-term results in patients with X-linked SCID.
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PMID:X-linked severe combined immunodeficiency. 193 18

This review article deals with the transfer of human lymphoid or hematopoietic tissues to severely immunodeficient mice to create new small animal models for the study of human biology and disease. The degree of functional reconstitution in the three current models is discussed. SCID mice with human grafts have been infected with human immunodeficiency virus (HIV) to generate a small animal model for AIDS research. Epstein-Barr virus (EBV)-related lymphoproliferative disorders can also be modeled by the transfer of adult peripheral blood mononuclear cells to SCID mice.
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PMID:Immunodeficient mice xenografted with human lymphoid cells: new models for in vivo studies of human immunobiology and infectious diseases. 197 49

Six human immunodeficiency diseases have been associated with the X chromosome by family studies. Genetic mapping with restriction fragment length polymorphisms (RFLPs) has permitted assignment of these diseases to specific loci on the X chromosome. Each of the disease entities maps to a single locus, confirming that the diagnostic criteria describe single diseases. X-linked chronic granulomatous disease and Wiskott-Aldrich syndrome map to loci on the short arm of the X chromosome; X-linked severe combined immunodeficiency, X-linked agammaglobulinemia, X-linked immunodeficiency with hyper-IgM, and X-linked lymphoproliferative syndrome map to loci on the long arm. Lyon's hypothesis predicts that these X-linked immunodeficiencies may be detectable in carriers of the diseases as a result of X chromosome inactivation of the normal disease gene. Four of the immunodeficiency diseases, X-linked agammaglobulinemia, X-linked severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and X-linked chronic granulomatous disease, affect cellular development so that carriers have a monomorphic population of immunocytes. The specific immunocyte development affected in carriers varies according to the disease. Genetic mapping of the diseases, with a collection of informative RFLPs, provides a tool that permits probability-based prenatal diagnosis. Carrier detection complements the RFLP-based genetic mapping, serving to confirm X-linkage in carriers.
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PMID:X chromosome linked immunodeficiency. 198 31

Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus-induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.
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PMID:Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report. 198 91

We describe three patients with Pneumocystis carinii pneumonia as the initial presentation of severe combined immunodeficiency disease. The pneumonia in the first patient was treated successfully with trimethoprim/sulphamethoxazole (Tmp/Smz). The second patient died despite therapy with Tmp/Smz and pentamidine. The third patient failed to respond to therapy with Tmp/Smz and pentamidine. He was subsequently treated with trimetrexate and leucovorin. Treatment with the new folic acid antagonist trimetrexate resulted in complete recovery. The case histories of these children serve to illustrate the clinical symptoms and new therapeutic modalities of P. carinii pneumonia in patients with immunodeficiency disease.
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PMID:[Pneumocystis carinii pneumonia in patients with a severe combined immunodeficiency]. 199 Mar

Occupational exposure to the human immunodeficiency virus (HIV) has led to a low but finite incidence of infection among health care providers. In such circumstances, postexposure administration of 3'-azido-3'-deoxythymidine (zidovudine; AZT) might be beneficial. To test this possibility, the SCID-hu mouse (the immunodeficient C.B-17 scid/scid mouse engrafted with human hematolymphoid organs) was treated with AZT at different times after intravenous infection with a standard dose of HIV (known to infect 100% of animals). If given within 2 h, AZT suppressed infection in all animals; if given after 2 days, no suppression was observed. At least in some animals, an AZT-sensitive phase lasted for as long as 36 h. These data support the hypothesis that prompt administration of AZT might be efficacious in suppressing acute HIV infection in humans. Further studies in the SCID-hu mouse might provide insight into treatment protocols of even greater efficacy.
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PMID:Postexposure prophylaxis with zidovudine suppresses human immunodeficiency virus type 1 infection in SCID-hu mice in a time-dependent manner. 199 34

We report the immunological characteristics of five patients with Omenn's syndrome, a rare inherited immunodeficiency also known as combined immunodeficiency with hypereosinophilia. The syndrome is characterized by T cell infiltration of skin, gut, liver, and spleen leading to diffuse erythroderma, protracted diarrhea, failure to thrive, and hepatosplenomegaly. Blood T cells as well as those infiltrating the skin and gut were found to express activation markers and were partially activated by mitogens but not by antigens. Although the lesions resembled those in graft-versus-host disease, the blood T cells were shown by DNA haplotype analysis using probes revealing variable number of tandem repeats to belong to the patients as well as the T cells infiltrating the gut and skin in one patient. A given T cell subset (TCR alpha beta+, CD4+/CD8+, or TCR gamma delta+) was predominant in each patient, with a specific distribution in the skin lesions. Moreover, the study of T cell receptor beta, gamma, and delta gene rearrangements in four patients revealed oligoclonality involving C beta 1, C beta 2, or different V gamma J gamma or V delta J delta genes. This indicates that restricted heterogeneity of the T cell repertoire, previously reported in one case, is a major feature of this syndrome. The occurrence of alymphocytosis-type severe combined immunodeficiency in the brother of one of the patients suggests that the restricted heterogeneity of T cell receptor gene usage in Omenn's syndrome may arise from leakiness, within the context of a genetically determined faulty T cell differentiation.
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PMID:Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). 201 May 48

Congenital deficiencies that involve the lymphocyte system are complex and represent abnormalities in genetic control or gestational development. Only the more common prototypes of these diseases will be discussed. Diseases of the B cell system presented include X-linked agammaglobulinemia, selective IgA deficiency, IgG subclass deficiency, and common variable immunodeficiency. T cell defects discussed are Di-George syndrome and severe combined immunodeficiency. Also mentioned briefly are HIV infection and the increasing problem of AIDS. Diagnostic evaluation and general principles of treatment of these diseases are considered.
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PMID:Evaluation and management of B and T cell abnormalities. 204 Apr 45

BMT can cure several congenital immunological defects: if in these disease the engrafting is easier, the GVH reactions are more frequent and severe. The possibility to deplete from T lymphocyte the marrow before infusion, has overcame this difficulty. From 1968 183 BMT have been performed in Europe on patients with SCID (70 from HLA-identical donor, 113 from HLA-nonidentical donor). The survival after 2 years is 76% in the first group, and 56% in the second group (100 marrows have been T-depleted with different techniques). Strict isolation procedures before the transplant are very important to achieve good results. The possibility to treat different immunodeficiency With BMT are also discussed.
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PMID:[Bone marrow transplantation in congenital defects of immunity]. 205 52

Inherited deficiency of the purine salvage enzyme adenosine deaminase (ADA) is responsible for approximately half the cases of autosomal recessive Severe Combined Immunodeficiency (SCID). Deficiency of ADA can also result in a much later-onset, milder immunodeficiency, while lesser degrees of enzyme deficiency can result in either late-onset immunodeficiency or grossly normal immunologic function. The full clinical spectrum of ADA deficiency is currently being more fully defined. Florid pathology is primarily restricted to the immune system and appears to result from accumulation of substrates (adenosine and deoxyadenosine) and metabolites (deoxy ATP). Studies indicate that these metabolites may preferentially accumulate in lymphoid cells and can interfere with lymphoid proliferation and function. There is evidence for several mechanisms, including induction of chromosome breaks, inhibition of ribonucleotide reductase needed for normal DNA synthesis, and inactivation of SAH hydrolase needed for normal methylation reactions. The enzyme is a 40 Kd monomer that is ubiquitous, and diagnosis can be made with many cell types including erythrocytes, lymphocytes and fibroblasts. Prenatal diagnosis has been made with chorionic villous samples, amniotic cells and fetal blood. The gene for ADA resides on the long arm of human chromosome 20, and both the expressed and structural gene have been isolated and characterized. Most patients with ADA SCID have single base pair mutations resulting in amino acid substitutions, although a splicing mutation and a deletion have been described. The treatment of choice is currently bone-marrow transplantation from a histocompatible related donor, if available. Haploidentical transplants have also been successful but appear to have higher failure rates in ADA deficients than in other types of SCID. Enzyme replacement, now using an enzyme modified to increase the half-life and decrease immunogenicity, has been reported as successful but longer-term efficacy remains to be evaluated. The disorder, despite its rarity, is for several reasons considered a prime candidate for gene therapy. Recently success has been obtained in introducing the gene into lymphoid stem cells and achieving long-term expression.
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PMID:Adenosine deaminase deficiency. 207 32


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