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

Primary immunodeficiency syndromes may be seen as "experiments of nature", giving insights into the organization and function of the human immune system. The principal categories of primary immunodeficiency syndromes: severe combined immunodeficiency, agammaglobulinemia and isolated T-cell defects (e.g. Di George Syndrome) are still used in view of their leading clinical presentations. However, detailed analysis of individual cases and families now shows a plethora of different diseases in each category. In this review the relationship of primary immunodeficiency diseases of the B-cell system and autoimmune phenomena are discussed. The pathology of thymus in severe combined immunodeficiency is shown: central maturation defects of the T-cell system are not due to "dysplasia" of the thymus but rather to enzyme defects of the lymphatic cells. Severe alterations of the thymus may also be caused by graft versus host disease. The clarification of genetic defects of lymphoid differentiation and maturation today may lead to improved early and prenatal diagnosis as well as specific gene therapy. The success of bone marrow transplantation in many cases of primary immunodeficiency disease syndromes may be considered as a consequence of successful gene therapy.
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PMID:[Inborn immunodeficiencies]. 172 40

This review focuses on recessive mutations at three loci whose gene products play critical roles in the development and regulation of the murine immune system. These mutations are: severe combined immunodeficiency (scid), osteopetrosis (op), and motheaten (me). The scid mutation blocks differentiation of functional T and B lymphocytes and interferes with DNA repair processes in multiple cell lineages. The normal gene product at this locus performs a critical function during antigen receptor gene rearrangement as well as during repair of double stranded DNA damage. Homozygosity for op causes impaired development of osteoclasts and other macrophage lineage cells. The op mutation is within the macrophage colony stimulating factor (Csfm) structural gene. Deleterious alleles at the me locus affect lymphoid as well as myeloid cell populations, causing severe immunodeficiency accompanied by systemic autoimmune disease. Determination of the product of the wild type allele at the me locus and the mechanisms by which mutations at this locus disrupt the immune system may reveal important new immunoregulatory processes.
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PMID:Hematopoiesis and models of immunodeficiency. 179 70

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
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PMID:Non-Hodgkin lymphoma in common variable immunodeficiency. 182 73

Primary membrane T cell immunodeficiencies (ID) have recently been characterized. In this paper we describe the main findings about the leukocyte adhesion deficiencies (LAD), the ID with low expression of the T cell receptor/CD3 complex, and the Omenn's syndrome. LAD is a consequence of mutations in the beta-chain-encoding gene of the leukocyte adhesion proteins. Functional consequences mainly affect phagocytic cells which are incapable of transendothelial migration. Effector T lymphocyte functions are, however, also impaired, i.e., helper T cell activity and cytotoxicity. The latter defect may account for the inability of LAD patients to reject HLA nonidentical bone marrow. Low expression of the T cell receptor CD3 complex is a rare entity characterized by a profoundly diminished expression of the whole complex on all T cells. The basic defect has not yet been unravelled. Interestingly, such T cells differentiate normally and can be activated by some antigens while anti-CD3 and anti-CD2 antibodies are not efficient. In five patients with Omenn's syndrome (combined immunodeficiency with eosinophilia), oligoclonal T cells were detected in blood, skin, and gut. These T cells are also in vivo activated. Since in one family, one sibling presented with typical SCID, i.e., alymphocytosis, and another with the Omenn's syndrome, it is proposed that the latter syndrome may correspond to a form of leakiness of SCID as found in the mice SCID model.
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PMID:Primary membrane T cell immunodeficiencies. 183 82

Deficiency of adenosine deaminase (ADA) results in severe combined immunodeficiency (SCID), a candidate genetic disorder for somatic cell gene therapy. Peripheral blood lymphocytes from patients affected by ADA- SCID were transduced with a retroviral vector for human ADA and injected into immunodeficient mice. Long-term survival of vector-transduced human cells was demonstrated in recipient animals. Expression of vector-derived ADA restored immune functions, as indicated by the presence in reconstituted animals of human immunoglobulin and antigen-specific T cells. Retroviral vector gene transfer, therefore, is necessary and sufficient for development of specific immune functions in vivo and has therapeutic potential to correct this lethal immunodeficiency.
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PMID:An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency. 184 69

A 7-year-old leukemic girl developed pancytopenia following chemotherapy and was given several transfusions of nonirradiated blood. Within 2 weeks she developed a maculopapular rash, fever, abnormal liver function, diarrhea, and wasting. She became septic and died 6 weeks later. Transfusion-associated graft-versus-host disease (GVHD) was suspected clinically. At autopsy, changes diagnostic of GVHD were present in the skin and liver. The remarkable feature of the case was the histopathology of the thymus, which was morphologically "dysplastic," i.e., minute, lymphoid depleted, devoid of a corticomedullary demarcation, and completely lacking in Hassall's corpuscles. These changes were virtually identical to those seen in the thymus of children with severe combined immunodeficiency disease (SCID). There was no evidence of preexisting immune deficiency. There is compelling experimental evidence that GVHD can produce changes in the thymus that are identical to those of "thymic dysplasia." These observations have led to the hypothesis that immunodeficiency associated with GVHD may stem, in part, from injury to thymic epithelium resulting in defective T cell maturation. As a corollary of this hypothesis, it has been suggested that the pathogenesis of some forms of SCID may involve GVHD-associated injury to the thymus by a maternal allograft acquired in utero. This report further documents thymic pathology in human GVHD and discusses these changes in the light of these ideas.
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PMID:Thymic involution with loss of Hassall's corpuscles mimicking thymic dysplasia in a child with transfusion-associated graft-versus-host disease. 186 63

In a female child with severe combined immunodeficiency, pure red cell aplasia was observed which required regular transfusions of erythrocytes. Parvovirus B 19 DNA (but no antibodies) was detected in stored serum samples after the death of the patient. We suggest that the anaemia was a consequence of parvovirus infection which persisted for at least 2 years due to the immunodeficiency.
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PMID:Persistence of parvovirus B19-DNA in blood of a child with severe combined immunodeficiency associated with chronic pure red cell aplasia. 191 97

From January, 1982, to July, 1990, 51 children with recurrent infections were investigated for immunodeficiency in this department by testing neutrophil function, lymphocyte subsets and serum immunoglobulin and complement concentrations. The prevalence of immune dysfunction within the group was 39% (20 of 51). A previously described clinical scoring system, which aims to identify children with a history of recurrent infection who merit investigation for immunodeficiency was also applied to all 51 children. The scoring system identified only 55% (11 of 20) of those with laboratory-proved immunodeficiency and had a false negative rate of 45% (9 of 20). This latter group included 2 children with severe combined immunodeficiency and 1 with hypogammaglobulinemia, diagnoses that one cannot afford to miss. The system was not sufficiently sensitive to be of use in deciding which child to test for immunodeficiency.
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PMID:Assessment of a clinical scoring system for detection of immunodeficiency in children with recurrent infections. 192 81

There are many examples of inherited immunodeficiencies characterized by normal differentiation of T and B lymphocytes but abnormal functions of these cells. Among them, combined immunodeficiency with defective expression in MHC class II genes was the first to be individualized. It is called MHC class deficient SCID by the WHO committee for the classification of immunodeficiency. It is an autosomal recessive disease with a severe evolution. Most of the 30 patients described died unless they were transplanted with HLA identical or HLA mismatched bone marrow. All HLA class II molecules (DR, DQ, and DP specificities) are absent on the cell surface in all tissues while HLA class I molecules are detectable. T and B cell abnormalities are characterized by defective in vivo and in vitro responses to antigens, although in vitro reactivity to mitogens is normal. These anomalies are considered as a direct consequence of the absence of HLA class II molecules on the surface of antigen-presenting cells incapable of sensitizing T cells. It was strongly suggested that MHC class II deficient SCID is due to a mutation that affects the regulation of the expression of all genes involved in the synthesis of MHC class II molecules.
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PMID:Combined immunodeficiency with defective expression in major histocompatibility complex class II genes. 193 8

A 4-year-old female with severe combined immunodeficiency (SCID) had normal numbers of T cells in circulation and normal T cell subsets. However, her T cells proliferated poorly to mitogens and did not proliferate to antigens or to anti-CD3 mAb. Interleukin-2 (IL-2) receptor expression was normal but IL-2 synthesis was undetectable. The addition of recombinant IL-2 to a mitogen-stimulated culture resulted in normalization of the proliferative response. Northern blot analysis of total RNA derived from the patient's T cells revealed a weak or absent expression of mRNA coding for IL-2, IL-3, IL-4, and IL-5. In contrast, there were normal amounts of mRNA coding for granulocyte-macrophage colony-stimulating factor (GM-CSF). Tumor necrosis factor and IL-6 production was also normal. Nuclear run on transcriptional assays revealed markedly decreased levels of newly initiated nuclear transcripts coding for IL-2, IL-3, IL-4, and IL-5 and normal levels of GM-CSF transcripts in patient relative to control lymphocytes. These results indicate that the patient's T cells suffered from a defect affecting the transcription of multiple T cell lymphokines and suggest that abnormalities affecting the production of T cell lymphokines may underlie some of the primary immunodeficiency diseases.
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PMID:Novel immune deficiencies: defective transcription of lymphokine genes. 193 9


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