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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primates infected with simian immunodeficiency virus (SIV) develop a condition similar to the human acquired immunodeficiency syndrome (AIDS). The close resemblance between the simian acquired immunodeficiency syndrome (SAIDS) and the human disease has led to the widespread use of SIV-infected monkeys as an animal model in the study of acquired immunodeficiency. We have investigated the use of standard anti-human antibodies for the immunohistochemical analysis of formalin-fixed, paraffin-embedded tissues from monkeys with SAIDS. With the exception of antibodies UCHL1 (CD45RO), MT1 (CD43), 4KB5 (CD45RA), and Ber H2 (CD30), our routine (human) lymphoma panel of markers worked successfully on the animal tissues. Using the anti-human antibodies, we were able to analyse the phenotypes of two cases of malignant lymphoma arising in a study group of 26 SIV-infected rhesus monkeys. Both of the cases stained with the antibodies WR16 (CD45RA) and L26 (CD20), and the B-cell lineage of the lymphomas was confirmed by the detection of IgA lambda immunoglobulin expression in one case, and IgM heavy chain in the other. We therefore report the successful use of anti-human antibodies in the immunohistochemical analysis of lymphomas arising in non-human primates infected with SIV.
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PMID:Phenotypic analysis of malignant lymphoma in simian immunodeficiency virus infection using anti-human antibodies. 191 70

A rapid whole blood test has been developed for circulating antibodies to human immunodeficiency virus type 1 (HIV-1), based on agglutination of autologous red blood cells. Evaluation of the test revealed that 100% of seropositive HIV-1 patients (both asymptomatic and AIDS cases) were detected (n = 94) with a specificity of 99.5% in healthy blood donors (n = 596). The assay uses an Fab fragment of a monoclonal antibody specifically directed against glycophorin (a transmembrane glycoprotein present on the surface of human red blood cells). This anti-red blood cell Fab is conjugated via the inter-heavy chain cysteines to a synthetic peptide corresponding to the immunodominant epitope of the HIV-1 viral coat protein gp41 (579-613). Addition of this reagent to 10 microliters of whole blood results in the Fab-peptide conjugate coating the red blood cells with peptide. In the presence of circulating antibodies to the HIV-1 peptide, red cell agglutination occurs within 2 min. The sensitivity and specificity of this reagent indicate that it is appropriate for use as a rapid diagnostic test for HIV-1 seropositivity.
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PMID:Rapid whole blood assay for HIV-1 seropositivity using an Fab-peptide conjugate. 201 40

CD4, the cell-surface receptor for the human immunodeficiency virus (HIV), is a member of the immunoglobulin (Ig) gene superfamily. It contains four extracellular sequences homologous to Ig VL domains. The first of these (V1) is sufficient for binding to HIV; however, the structural basis for this binding has yet to be elucidated. While several models for the structure of Ig-like domains in CD4 have been proposed on the basis of crystal structures of Ig VL domains, direct evidence that CD4 and VL domains fold similarly has not been obtained. To produce individual domains of CD4 for structural studies, we used molecular fusions of such domains with Ig heavy chain (CD4 immunoadhesins), which are very efficiently expressed and secreted in mammalian cells and can be easily isolated in single-step purification with protein A. Since these fusion molecules are antibody-like homodimeric proteins, we investigated the possibility that they might be cleaved enzymatically to produce Fd-like and Fc fragments. We found that cleavage with papain releases an Fd-like fragment containing the V1 and V2 CD4 domains; this fragment fully retains the ability to bind to the HIV-1 envelope glycoprotein gp120 and to block HIV infection in vitro. Moreover, folding of the CD4 domains in the Fd-like fragment and in the parent immunoadhesin is indistinguishable, as indicated by circular dichroism. Spectral analysis of the Fd-like fragment suggests that secondary structure content is identical with that predicted from the known structure of Ig VL domains; this directly supports the hypothesis that the V1 and V2 domains of CD4 fold similarly to Ig VL domains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzymatic cleavage of a CD4 immunoadhesin generates crystallizable, biologically active Fd-like fragments. 212 84

Recurrent pyogenic infections are the leading clinical symptom in patients with antibody deficiency syndromes. In accordance with the WHO-classification at least nine different diseases are differentiated. In some cases diagnosis can be made simply by determining the immunoglobulin serum levels. Some diseases, such as Ig-heavy chain gene deletions, are clearly characterized by molecular biological methods, while other terms, such as common variable immunodeficiency, cover a collection of different diseases with changes predominantly of B-cell functions. The main features of the antibody deficiency syndromes are described. In most cases adequate therapy can be achieved by IgG replacement therapy.
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PMID:[Primary antibody deficiency syndrome. Improved life expectancy and immunoglobulin G substitution]. 222 50

The pattern of immunoglobulin (Ig) gene rearrangement and the genomic structure of the Myc locus were investigated in the DNA of 20 lymphnode biopsies of patients suffering from lymphoadenopathy-associated syndrome (LAS) and from 3 patients with Burkitt's lymphoma. Although polyclonality was the prevalent pattern of Ig gene rearrangement observed in LAS, in 30% of the cases discrete bands of Ig heavy chain gene rearrangement were identifiable due to the presence of monoclonal or oligoclonal cell populations. However, structural alterations of the Myc gene were not detected in any cases. As expected, in all three Burkitt's lymphomas studied, the lymphnode DNA displayed a clonal pattern of Ig heavy chain gene rearrangement. The Myc was altered in two cases, which presented a truncation of the gene beginning within a very short region of the first intron. By contrast, the breakpoint positions on chromosome 14 mapped in different regions of the Ig loci, which in both cases involved the switch (SH) area. Data confirm the relatively common occurrence of oligoclonal expansions within B cells in LAS and the frequent involvement of the Myc oncogene in the process of lymphomagenesis in individuals positive for human immunodeficiency virus (HIV).
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PMID:Immunoglobulin and Myc gene structure in lymphnode biopsies from HIV-positive patients with LAS and lymphoma. 238 73

The definition of IgG subclass deficiency and the correlations between low IgG subclass serum concentrations and high incidence of infections in certain patients are still obscure. Therefore 260 children from 6 months to 18 years with severe recurrent infections or a known immunodeficiency were screened for IgG subclass deficiency. Nine patients with severe IgG2 deficiency (Ig2 less than 0.3 g/l) and 35 patients with non-detectable IgG4 in immunoprecipitation were detected. One of these patients had a concomitant IgA deficiency, eight revealed an additional IgA and IgG2 deficiency, two an IgA, IgG2, and IgG3 deficiency, eighteen an IgG2 deficiency and one patient an IgG2 and IgG3 deficiency. The proportion of patients with non-detectable IgG4 in immunoprecipitation was 13.5% and thus in the same order of magnitude as described in the literature for healthy people. Our data show that there is no relation between low IgG4 serum levels and the increased occurrence of severe infections. In all patients investigated with non-detectable IgG4 in immunoprecipitation the gene for the heavy chain gene constant domain C gamma 4 could be detected by Southern blotting. Using a sensitive ELISA method IgG4 could be directly demonstrated in all patients at a serum level of 0.5-29 micrograms/ml. Specific IgG4 antibodies against protein antigens could not be detected in IgG4-deficient patients. Nevertheless total IgG antibodies against diphtheria and tetanus toxoid reached protecting titers. Patients with IgG2 deficiency showed an impaired immune response against polysaccharides from pneumococci and haemophilus influenzae type b.
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PMID:[IgG subclass deficiency in childhood. Changes in the antigen specific immune response and significance of low IgG4 level]. 245 Nov 27

The development of high-grade, malignant B-cell lymphoma is a well-recognized complication of human immunodeficiency virus (HIV) infection. Plasma cell neoplasms, however, have been rarely encountered in HIV-infected people. This study presents the morphologic and immunologic features of an unusual plasma cell tumor occurring in a 31-year-old HIV-antibody-positive male. The malignancy was characterized by widespread dissemination and hypercalcemia at presentation and a clinically aggressive course. Immunoperoxidase staining of tumor tissue obtained from biopsy and at autopsy had positive results for IgM and lambda. In the patient's serum, only an IgG kappa paraprotein was detected, indicating that the tumor was nonsecretory. DNA analysis of autopsy-derived tumor tissues demonstrated clonal rearrangements of the immunoglobulin (Ig) heavy chain gene locus and rearrangements in both kappa and lambda light chain gene loci. Furthermore, DNA hybridization studies revealed the presence of Epstein-Barr virus (EBV) genomes in tumor tissue but not in nontumor tissue from this patient.
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PMID:Plasma cell malignancy in the acquired immune deficiency syndrome. Association with Epstein-Barr virus. 254 9

A 3-year-old boy who developed common variable immunodeficiency was investigated for the development of hypogammaglobulinaemia. During a period of 4 years, the combined deficiency of IgA, IgG2 and IgG4 proceeded to include IgG1 and finally IgG3 and IgM. This order of isotypes of IgG subclass deficiencies corresponded to the gene order for the heavy chain constant region for immunoglobulins on chromosome 14.
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PMID:Development of hypogammaglobulinaemia in a patient with common variable immunodeficiency. 261 5

An area of great controversy in molecular immunology is the mechanism by which the differential expression of secretory and membrane immunoglobulin heavy chain is regulated during B cell development. Since the changes in expression of the two proteins are determined largely by the steady state levels of the mRNAs that encode them, recent work has focused on the regulation of the expression of the two messages. This problem is central to understanding humoral immunity, with the specific antigen driven switch from antibody as receptor to antibody as secreted product and may be of direct relevance to some forms of the common variable immunodeficiency syndrome. In addition, numerous other genes have been shown to be regulated by alternative RNA processing. Since its beginnings, research in immunology has brought about profound changes in our view of biology. Jenner's landmark experiment, inducing a minor illness to prevent a major one, showed that the body's future susceptibility to a particular disease could be manipulated. More recently the demonstration that immunoglobulin V, D, and J gene segments, originally spread over many kilobases (kbs) in the genome, must be assembled to form a functional heavy chain gene has shattered both the concept of a genome fixed at fertilization and the "one gene, one protein" rule. The alternative processing of heavy chain transcripts to produce secretory and membrane forms of immunoglobulin has demonstrated how the same gene can give rise to proteins with alternative structures. Since the discovery of the role of alternative RNA processing in heavy chain mRNA synthesis, numerous other cellular genes have been shown to be regulated by modulation of RNA processing pathways.
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PMID:Regulation of the production of secretory and membrane immunoglobulin during lymphocyte development. 264 62

We have examined the potential of IFN-gamma to ameliorate the physiologic defect of CGD by studying its effects on CGD phagocyte superoxide generation, NADPH-oxidase kinetics, and expression of the gene for the phagocyte cytochrome b heavy chain. In vitro treatment with IFN-gamma increased the respiratory burst activity of PMN and macrophages from three patients in two kindreds with type IA (variant, X-linked). Phagocytes from type I (classic, X-linked) and types IIA and III (autosomal recessive) CGD did not respond to IFN-gamma in vitro. Preliminary studies of in vivo treatment of several of the same patients with subcutaneous IFN-gamma demonstrated similar responses. All subjects whose phagocytes had responded in vitro showed complete or partial correction of the CGD defect in superoxide generation for up to 1 month after IFN-gamma administration. One patient with type I CGD with no detectable in vitro response also showed improved phagocyte respiratory burst activity after in vivo IFN-gamma treatment. These studies establish the potential efficacy of IFN-gamma in the treatment of patients with X-linked CGD and provide an example of pharmacologic modulation of gene expression in human disease. The ease of administration and absence of toxicity suggest a place for IFN-gamma as an adjunct to more conventional antimicrobial therapy during acute infections in CGD and perhaps even other congenital and acquired immunodeficiency states.
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PMID:Cellular and molecular effects of recombinant interferon gamma in chronic granulomatous disease. 283 59


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