Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reproducibility of a simplified, sensitive and rapid agarose-cell droplet assay for leucocyte migration inhibition factor (LIF) activity was studied. Removal of T cells with anti-T-cell serum eliminated LIF activity, indicating that in humans it is probably the T cell that produces LIF. Cord blood lymphocytes produce LIF, although spontaneous migration of leucocytes is less than in older children. The cause of this apparently does not reside in the PMN leucocytes. Studies of children with immunodeficiency suggest that the T-cell population in humans is heterogenous. B-cell deficiencies such as hypogammaglobulinaemia, have normal PPD and PHA induced LIF production, whilst some patients with ataxia-telangiectasia have defective PPD LIF activity, their PHA LIF activity being only minimally depressed. On the other hand, Down's syndrome patients with reduced blood T cells have remarkably deficient LIF activity to PHA and relatively good activity to PPD. Children receiving steroid therapy lose much of their ability to produce LIF to the specific antigen PPD, but not to the non-specific mitogen PHA.
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PMID:Leucocyte migration inhibition factor (LIF) production by lymphocytes of normal children, newborns, and children with immune deficiency. 13 10

We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function.
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PMID:Selective defects in T cell function in ataxia-telangiectasia. 15 50

The eldest brother in a sibship of five children died of acute myelogenous leukemia at 10 years of age. The second and third eldest brothers died of hypoplastic anemia at ages five and nine years, respectively. A surviving 6 year old brother, the proband of the study, has abnormalities that suggest a preleukemic state: mild pancytopenia, platelet dysfunction, immunodeficiency, and bone marrow hypoplasia with approximately 18 per cent blast forms. His 17 year old sister has a mild normochromic normocytic anemia. Cytogenetic studies revealed C-group monosomy in the bone marrows of the proband and the third brother (45, XY, -C); band studies demonstrated that a No. 8 chromosome was missing in the proband (45, XY, -8). At least four of the siblings and their father had cerebellar ataxia, and evidence of a small cerebellum at autopsy examination or by computerized axial tomography. The disorder in this family has major features of two autosomal recessive preleukemic diseases, ataxia-telangiectasia and Fanconi's anemia. However, these and other inherited conditions were excluded by clinical or laboratory criteria, and no environmental causes of the familial disorder were found. The constellation of abnormalities in the family may constitute a new genetic syndrome.
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PMID:A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy. 28 89

Autoimmune disorders are reportedly more frequent than expected in immunodeficient patients and in their relatives. The hypothesis that genetic factors related to immunodeficiency may predispose to the development of autoimmunity was studied in relatives of patients with variable immunodeficiency (VID), ataxia-telangiectasia (A-T), or X-linked infantile agammaglobulinaemia (X-LA). Close relatives of patients with VID or A-T had thyroid and gastric autoantibodies significantly more frequently than did control subjects. No abnormalities were detected in unaffected relatives of X-LA patients. The increased incidence of organ-specific autoantibodies in close relatives of VID patients was confined to those families with more than one member with immunodeficiency. These data suggest that there are at least two forms of VID, one of which is associated with familial autoimmunity. It is postulated that heterozygous carriers of the A-T gene and persons with genes involved in the development of VID may exhibit T-lymphocyte dysfunction which predisposes them to autoimmunity.
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PMID:Autoimmunity in the relatives of patients with immunodeficiency diseases. 89 Oct 19

The clinical and radiographic features of twenty-two cases of ataxia-telangiectasia are reviewed. Severity of pulmonary manifestations tended to correlate closely with severity of immunodeficiency. Observations are made upon the problem of intercurrent malignancy in ataxia-telangiectasia. The radiographic studies of patients seen at the National Institutes of Health with A-T were reviewed retrospectively and correlated with degrees of immunodeficiency determined clinically. Three fairly distinct groups with high, intermediate and low incidence of sinopulmonary disease were found. Comment is made on the problem of increased malignancy in A-T and possible clues in the detection by the radiologist.
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PMID:Ataxia-telangiectasia. 95 65

Although an isolated clinical case report was published in 1926 and another in 1941, ataxia-telangiectasia (A-T) was not established as a distinct entity until 1957, when it was first delineated clinicopathologically. Susceptibility to sinopulmonary infection was identified as the main cause of death and as the third major component of the syndrome; its heredofamilial nature was documented, and it was designated "ataxia-telangiectasia." In a later review of 101 published cases, lymphoreticular malignancy emerged as the second most frequent cause of death. Although the thymus was found to be absent in the first reported autopsy in 1957 and the serum IgA deficiency was first recorded in 1961, A-T was not established as an immunodeficiency disease until 1963. Thymic abnormality and dysgammaglobulinemia explain the 2 main causes of death, sinopulmonary and neoplastic, but the immunodeficiency is probably not the central defect. It does not appear to explain either of the 2 main clinical diagnostic keys, the ataxia and the telangiectasia, or any of the other seemingly unrealted multisystemic facets of this complex disorder. Some of our most provocative long-term clinical observations and recent pathologic findings in our series of 9 autopsies are discussed.
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PMID:Ataxia-telangiectasia: some historic, clinical and pathologic observations. 109 82

Ataxia telangiectasia (AT) is a multiform genetic disease characterized by immunodeficiency, cerebellar abnormalities, and cancer predisposition. Heterozygotes also have an increased risk of developing several different cancers. It has been estimated that as many as 18% of all patients with breast cancer, the cancer most clearly associated with AT heterozygotes, may be carriers of the AT gene. We describe an assay for AT heterozygotes that relies on the previous observation that cells from AT homozygotes show a greater and more prolonged radiation-induced accumulation in the G2 phase of the cell cycle than do normal controls. We showed that all 6 A-T heterozygotes show a greater extent of G2 phase delay at different times postirradiation than do controls. The degree of accumulation was less than that observed in AT homozygotes. Only two of 22 controls showed overlap with heterozygotes at 18 hours postirradiation, and that number was reduced to one at the 24-hour point. As a group, AT heterozygotes were intermediate between controls and AT homozygotes at both time points after irradiation. This assay is relatively simple and reliable and can be performed in any laboratory with access to both Epstein-Barr virus (EBV) for transformation of lymphocytes and a fluorescence-activated cell analyzer.
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PMID:Enhanced levels of radiation-induced G2 phase delay in ataxia telangiectasia heterozygotes. 131 83

Immunofluorescent flow cytometric examination of one hundred and eighty-five children with different primary immunodeficiency syndromes and sixty-nine control patients revealed twenty-six cases with a bimodal distribution of antigens CD5 and CD7. Such abnormalities were most frequently found in patients with total antibody deficiency, namely those with common variable hypogammaglobulinaemia (10/24 patients) and congenital agammaglobulinaemia with lack of B cells (10/40), but were never seen in normal controls. Two-colour flow immunofluorescence demonstrated that antigen CD4 was expressed only on intensely fluorescent CD5+ cells, irrespective of the immunodeficiency state. Antigen CD4 was detected on cells with both high and low expression of antigen CD7, but a small percentage (2%-5%) of CD4+ lymphocytes did not belong to the CD7+ population. Antigen CD8 was found equally on intensely and weakly fluorescent CD5+ and CD7+ cells. In some immunodeficient patients suffering from ataxia-telangiectasia (12/36) and in some with Wiskott-Aldrich syndrome (2/6) there was a significant excess (greater than 20%) of CD7+ over CD5+ cells. In these patients a considerable number of the CD8+ cells were not part of the CD5+ population, but were always part of the CD7+ population. Cell populations with the phenotype CD5-, CD7+ consisted mainly of lymphocytes showing weak expression of antigen CD8.
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PMID:Two-colour flow cytometry study of lymphocyte subpopulations in patients with primary immunodeficiencies. 171 14

It is the purpose of this review to analyse prevalence and pathogenesis of tumours occurring in the diverse conditions of primary and secondary immunodeficiencies. In general, most states of immunodeficiences are connected with a highly increased tumour risk. However, there is circumstantial evidence that immunodeficiency-related malignancies do not primarily result from an impaired immunosurveillance. With special regard to ataxia-telangiectasia it has been found that congenital chromosomal instability deregulates the maturation of immunocompetent lymphoid cells by interfering with their natural DNA rearrangements and eventually leads to false recombinatory events with oncogenetic consequences in a parallel way. Malignancies in primary common variable or in secondary (e.g. AIDS) immunodeficiency may result from an impaired immunity to oncogenic viruses or from chronic immune damage due to secondary autoimmune disorders.
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PMID:[Tumors in immunodeficiency syndromes]. 172 56

Ataxia-telangiectasia is a syndrome with many facets, involving a progressive cerebellar ataxia, immunodeficiency, cancer susceptibility, radiosensitivity, defects in DNA repair/processing, chromosomal breakage and rearrangements, elevated serum alphafetoprotein, and premature aging. Ataxia-telangiectasia is an autosomal recessive disorder, rare in outbred populations; carriers of the ataxia-telangiectasia gene may be as common as 1 in 60 and have subclinical radiosensitivity and cancer susceptibility. One estimate suggests that 8.8% of patients with breast cancer could be carriers of ataxia-telangiectasia. These carriers may be responsible for underestimating normal tolerance doses for radiation therapy by 15% to 20%; thus by preselecting and excluding carriers of ataxia-telangiectasia from cohorts of patients with cancer, conventional radiation doses might be increased so as to improve greatly the efficacy of radiotherapy. The genes for the 3 most common ataxia-telangiectasia complementation groups, which include 97% of tested families, have recently been localized to the long arm of chromosome 11.
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PMID:Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis. 200 80


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