Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

CNA/N mice bearing the X-linked immunodeficiency (xid) gene(s) demonstrate overall decreased numbers of B-cells, impaired immune responses to TI-2 antigens and decreased serum IgM, IgG3 and to a lesser extent IgG1 and IgA. In these experiments we examined equal number of B-cells (cells capable of regeneration of surface Ig) from PP, MLN and spleens of xid and control mice for immunoglobulin gene expression. B-cells present in CBA/N mice exhibit control levels of Ig isotype-specific mRNA accumulation and transcription. Oligonucleotide probes directed against membrane and secreted exons of mu, gamma and alpha genes were synthesized and hybridized to B-cell RNA from CBA/N and CBA/J mice to determine relative levels of each isotype- and exon-specific mRNA. Results revealed decreased alpha s RNA: alpha m RNA in splenic B-cells of xid mice when compared to control animals. Northern blot analysis of total tissue polysomal RNA demonstrated enhanced expression of the (larger) membrane form of alpha-mRNA (alpha m-RNA) of CBA/N when compared to CBA/J mice. This was especially apparent in splenic preparations; these and other studies have shown that both control and xid PP and MLN express enhanced levels of the membrane forms of each Ig heavy chain isotype RNA when compared to splenic RNA levels. These data suggest the presence of a defective regulation of membrane and secreted alpha in B-cell subpopulations of xid mice.
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PMID:Immunoglobulin gene expression in xid mice: defective expression of secreted and membrane alpha-heavy chain RNA. 311 16

An infant with congenital human immunodeficiency virus (HIV) infection had immune thrombocytopenic purpura (ITP) develop at four months of age. A bone marrow aspirate had normal results in morphologic characteristics and cellularity. Flow cytometry analysis of the marrow cells showed that the predominant cell in the "lymphocyte" cluster was of B-lineage and common acute lymphocytic leukemia antigen (CALLA) positive. Southern blot analysis of marrow DNA demonstrated gene rearrangements in both the immunoglobulin (Ig) heavy chain and kappa light chain loci, confirming the presence of a clonal B-cell lymphoid proliferation. At one year of age the patient is clinically well without evidence of malignant lympho-proliferative disease. This case exemplifies a limited clonal B-cell expansion in the bone marrow of a patient with HIV infection and a benign hematologic condition.
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PMID:Clonal B-cell proliferation in an infant with congenital HIV infection and immune thrombocytopenia. 326 38

Human-human B cell hybridomas constructed from B lymphocytes of common variable immunodeficiency (CVI) patients and the nonsecreting cell line WIL2/729 HF consistently secrete low levels of Ig and appear to retain a defect characteristic of the CVI patient's B cells. We assessed the differentiative capacity of retinoic acid (RA) on these hybridomas, as well as on hybridomas constructed from normal B cells and from patients with selective IgA deficiency. RA at concentrations varying between 10(-5) and 10(-9) M augmented IgM secretion 4-20-fold from four of four CVI hybridomas tested, but did not affect Ig secretion from normal or IgA-deficiency hybridomas. In support of this elevated Ig secretion, RA enhanced the de novo synthesis of biosynthetically labeled light (kappa) and heavy (mu) Ig (up to 4- and 15-fold, respectively) in the CVI hybridoma line JK32.1. The increase in IgM synthesis/secretion could not be accounted for by RA-induced alteration in the cell cycle. In inducing this increase in IgM production, RA was found to affect two aspects of Ig gene expression: (a) the steady-state levels of heavy and light chain mRNAs were enhanced, and (b) the processing of mu heavy chain transcripts to the secreted mRNA form became favored over the membrane mRNA form. We also show that expression of Leu-17 (CD38), a surface marker that is re-expressed in the late pre-plasma stage of B cell development, was increased by RA from less than 20% to greater than 90% of the total cell population, with a concomitant 4-10-fold augmentation in the mean fluorescence intensity. Changes in both Leu-17 expression and de novo Ig synthesis were prominent by 24 h, but could be observed as early as 8 h after induction. Taken together, our study demonstrates that RA affects a marked alteration in the differentiated state of the CVI hybridoma clones. This finding suggests that retinoids can enhance the functional capabilities of B cells with defects in maturation and support further studies to evaluate their clinical potential in CVI.
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PMID:Retinoic acid induces the differentiation of B cell hybridomas from patients with common variable immunodeficiency. 329 36

Serum IgG subclass levels are reported on 70 patients with known primary immunodeficiency syndromes. Analysis of the data on the 28 patients with common variable immunodeficiency suggest that the deficit in subclasses is not generally proportionate. Some subclasses appear to be more strongly affected than others. The pattern suggests a hierarchical involvement with the order: IgG4 greater than IgG2 greater than IgG1 greater than IgG3. There appears to be a closer relationship between IgG1 and IgG3 levels than between IgG2 and IgG3 or IgG1 and IgG2 levels. The data are consistent with the hypothesis that there is a sequential increasing impediment of the programmed cascade for downstream heavy chain constant region gene rearrangements.
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PMID:IgG subclass levels in the serum of patients with primary immunodeficiency. 377 16

Patients with an autosomal recessive combined immunodeficiency are characterized by an HLA negative phenotype of activated T and B lymphocytes. To determine the molecular basis of this syndrome we have studied the biosynthesis of class I and II antigens and the expression of relevant genes in these patients. The synthesis of the HLA A, B, and C heavy chain is markedly decreased, while beta 2 microglobulin is made in normal amounts. Biosynthesis of HLA-DR alpha-chain and beta-chain is abolished in the lymphocytes of these patients and there is a total absence of mRNA for either alpha-chains or beta-chains of HLA-DR. This indicates that the lack of class II antigen on these lymphocytes results from a block in the expression of HLA-DR genes. The Ii-chain, the invariant polypeptide associated intracellularly with HLA-DR, and its mRNA are made in normal amounts. Since the structural genes coding for class II polypeptides do not seem to be affected, the reported genetic defect in the patients concerns the regulation of the expression of HLA-DR genes.
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PMID:A defect in the regulation of major histocompatibility complex class II gene expression in human HLA-DR negative lymphocytes from patients with combined immunodeficiency syndrome. 386 May 9

Primary central nervous system lymphoma constitutes one of the criteria for the acquired immune deficiency syndrome (AIDS), yet a paucity of information is currently available regarding the clinical, immunologic, or pathologic features of these patients. Six homosexual men presenting with primary central nervous system lymphoma were evaluated. Five of these patients presented with altered mental status. All lymphomas were intracranial. B cell immunoblastic sarcoma was found in five. Immune phenotyping studies performed in five patients revealed monoclonal lambda light chain in three, whereas one expressed only IgG heavy chain, and one demonstrated another B cell (LN-1) surface antigen. Hypodense, contrast-enhancing lesions were apparent on computed axial tomographic scanning of the brain, in sharp contrast to isodense or hyperdense lesions reported in primary central nervous system lymphomas without underlying immunodeficiency. Immunologic abnormalities in these patients were similar to those in AIDS presenting as Kaposi's sarcoma or with opportunistic infections. In spite of therapeutic interventions, survival was short, and only one patient is currently alive.
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PMID:Primary central nervous system lymphoma in homosexual men. Clinical, immunologic, and pathologic features. 387 74

Human-human B cell hybridomas have been established from the peripheral blood lymphocytes of patients with common variable immunodeficiency (CVI) by fusion with an HGPRT-negative B lymphoblastoid cell line. IgM-secreting hybridomas were successfully obtained from CVI lymphocytes after stimulation for 5 days in vitro with a combination of PWM and Staphylococcus aureus strain Cowan I. Fusion of peripheral blood lymphocytes that were stimulated for 5 days in vitro with a single mitogen resulted in no viable hybrids from a total of 600 X 10(6) CVI lymphocytes. The combination of PWM and Cowan I did not induce appreciable Ig secretion from the CVI lymphocytes during the 5-day course, although it did so in normal lymphocytes. After the 5-day stimulation with this mitogen combination, however, a large percentage of the original number of peripheral blood cells were recovered, and these had a fusion frequency of approximately 1 to 2 per 10(6) with the B lymphoblastoid line. Fifteen cloned IgM-secreting hybridomas have been isolated from five different CVI patients. These hybridomas are tetraploid and have been stable in culture for 6 to 12 mo. All of the hybridoma lines that were examined contain a functionally rearranged IgM heavy chain gene from the B cell parent of the CVI patients. These human-human B cell hybridoma lines will enable a more thorough characterization of the B cell defects involved in CVI at the cellular and molecular levels.
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PMID:Human-human B cell hybridomas from in vitro stimulated lymphocytes of patients with common variable immunodeficiency. 631 3

We determined the B cell subpopulations that produce the major cross-reactive idiotype (CRIA) associated with the anti-phenylarsonate (ARS) antibody response of A/J mice. Specifically, we examined the B2 subpopulation found in normal mice which, in H-2b mice, bears the I-Ab-encoded determinant Ia.W39; the B1 subpopulation found in mice expressing the CBA/N X-linked immunodeficiency trait (xid); and the B1 subpopulation found in normal mice after the cytotoxic elimination of B2 cells with anti-Ia. W39 and complement. CRIA is expressed in each of these B cell subpopulations. Antigen plays a selective role in the stimulation of distinct B cell sets. ARS conjugates of keyhole limpet hemocyanin (KLH) can activate both the B1 and B2 subpopulations. In contrast, ARS conjugates of synthetic polypeptides under Ir gene control selectively activate the B2 subpopulation in strains that are genetic responders to the carrier. This leads to the establishment of CRIA dominance where CRIA+ anti-ARS antibody is 70 to 95% of the total anti-arsonate antibody response. This class of antigens fails to activate the B1 cells in either normal or xid mice. We compared the CRIA+ antibody produced by selectively activated B2 cells to that produced by the B1 subpopulation in xid mice. For these comparisons, we used competitive radioimmunoassays that employed polyspecific anti-CRIA antiserum or monoclonal anti-CRIA antibodies specific for distinct idiotopes on the heavy chain of CRIA+ antibody. B2 cells produce a CRIA+ anti-ARS antibody that is idiotopically uniform among individual mice, and that closely approximates the hybridoma protein 36-65 (the heavy chain of 36-65 represents the germ line-encoded sequence of the unique CRIA structural gene (25]. In contrast, the CRIA+ antibody produced by the B1 cell subset of xid mice is idiotopically diverse among individual mice, and differs markedly from the 36-65 hybridoma protein. The extent of diversification found in CRIA+ antibody depends on the B cell subpopulation that produces it.
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PMID:Selective activation by thymus-dependent antigens of distinct B cell subpopulations expressing a major cross-reactive idiotype. 643

The existence of specific probes for human genes makes it feasible to study genetic abnormalities, both inherited and acquired, at the level of the genome. In this respect, the antibody genes of man are of particular interest as they represent a multigene family expressed in many leukaemias and immunodeficiency diseases. Furthermore, selective deficiency of immunoglobulins has been described in healthy individuals. Normally, human adults express five types of immunoglobulin--IgM, IgD, IgG, IgE and IgA (defined by the class of heavy chain constant region). Subclasses are also known in IgG (IgG1, IgG2, IgG3 and IgG4) and IgA (IgA1 and IgA2) in which the immunoglobulins contain gamma 1, gamma 2, gamma 3 or gamma 4 and alpha 1 or alpha 2 CH regions, respectively. Recently, a healthy Tunisian person was described who showed abnormal patterns of immunoglobulin expression. The serum immunoglobulin of this individual, designated TAK3, was confined to IgM, IgD, IgG3, IgE and IgA2. We have now used cloned CH-gene probes to study the DNA of TAK3 as well as two brothers, also Tunisian but apparently unrelated to the individual TAK3, and who show a similar immunoglobulin abnormality. We found that in these cases there seems to have been a large chromosomal deletion which includes three gamma genes, an alpha gene and a pseudo-epsilon gene. This deletion accounts for the simultaneous absence of certain H-chain subclasses. These results illustrate that the human immunoglobulin gene locus is capable of undergoing rapid change, which is particularly apparent within small populations in which consanguinity is common.
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PMID:Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. 681 43

Experiments were carried out to assess the role of naturally acquired antibody-specific immunoregulation in the immunodeficiency of aged individuals. It was found that greater than 50% of the primary dinitrophenyl-specific BALB/c B cells did not respond in carrier-primed 2-yr-old BALB/c adoptive hosts as compared with similarly primed younger recipients. Similar suppression was observed in carrier-primed younger BALB/c mice that had received 4 x 10(7) spleen cells from 2-yr-old BALB/c mice, as opposed to those that had received 4 x 10(7) spleen cells from younger mice. This diminution in responsiveness was noted only for syngeneic BALB/c B cells because B cells of strains differing from BALB/c in the heavy chain allotype-idiotype locus were not suppressed. These findings indicate that old, but not young, mice had developed the capacity to suppress primary B cells bearing receptors expressing much of the syngeneic antibody repertoire. This suppression may play an important causative role in the relatively poor humoral immune responsiveness of aged individuals.
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PMID:Antibody-specific immunoregulation and the immunodeficiency of aging. 697 8


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