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)

Interleukin-1 (IL-1) production by endotoxin-stimulated, cultured monocytes from 19 patients with lethal congenital immune disorders were studied and compared with normal controls. Lipopolysaccharide (LPS) stimulated IL-1 production was normal in three of three patients with Wiskott Aldrich syndrome (WAS), two of three combined immunodeficiency with T-cell predominance (CIDTP) and nine of 13 with severe combined immunodeficiency (SCID). Monocytes deficient in IL-1 production could be restored to normal production after incubation with indomethacin in three of five deficient patients. Monocytes from the other two patients could not be induced to generate IL-1, suggesting either an intrinsic deficiency or an alternate inhibitory mechanism as the basis for the IL-1 deficiency observed. In patients with SCID who were transplanted with HLA-haplotype disparate, T-cell depleted marrow without preparative chemotherapy, deficiency of monocyte IL-1 production was correlated with graft failure. Immune reconstitution was achieved in IL-1 deficient patients only when donor monocytes were also engrafted. We hypothesize that deficiencies of IL-1 production may contribute to the heterogeneous expression of combined immunodeficiencies, and may also restrict the engraftment and functional development of allogeneic lymphoid progenitors from a T-cell depleted marrow graft.
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PMID:Correlation between interleukin-1 production and engraftment of transplanted bone marrow stem cells in patients with lethal immunodeficiencies. 256 39

A sicca syndrome with parotid enlargement, pulmonary insufficiency, and lymphadenopathy was seen in 12 patients infected with human immunodeficiency virus (HIV), only 1 of whom has had an opportunistic infection during 304 patient months of study. There was a striking increase in numbers of circulating CD8 lymphocytes and the prevalence of HLA-DR5 was greatly increased. In patients with this diffuse infiltrative lymphocytosis syndrome (DILS) the CD8 lymphocytosis, which probably depends on histocompatibility antigen status, may influence disease progression in HIV infection.
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PMID:A sicca syndrome in HIV infection: association with HLA-DR5 and CD8 lymphocytosis. 257 Oct 58

IgA deficiency and common variable immunodeficiency are heritable disorders that can occur within the same family. Both immunodeficiencies are characterized by arrests in B-cell differentiation that vary in the extent of the immunoglobulin isotypes involved. A high frequency of major histocompatibility complex supratypes associated with a null allele of the gene encoding the C4A isotype of complement component C4 has been observed in IgA-deficient individuals. In search of a genetic linkage between the two immunodeficiencies, we examined the major histocompatibility complex (MHC) class III genes encoding complement components C2, C4A, and C4B and steroid 21-hydroxylase in addition to the HLA serotypes in individuals with either common variable immunodeficiency or IgA deficiency. Twelve of 19 patients with common variable immunodeficiency (63%, P less than 0.001) and 9 of 16 patients with IgA deficiency (56%, P less than 0.01) had rare C2 alleles and/or C4A and 21-hydroxylase A deletions, whereas these gene features were seen in only 5 of 34 healthy individuals (15%) in the control group. Nine of 11 patients with C4A deletion had an HLA haplotype consistent with the MHC supratype HLA-A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3 previously found to be associated with IgA deficiency. The data support the hypothesis that common variable immunodeficiency and IgA deficiency are related disorders, susceptibility to which is determined by a gene(s) within or near the MHC class III gene region on chromosome 6.
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PMID:Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes. 257 59

A female infant with DiGeorge syndrome associated with severe T-cell immunodeficiency underwent a successful bone marrow transplantation from her HLA-identical, mixed leukocyte culture-nonreactive brother at 5 months of age. Mature circulating T cells and mitogen-induced proliferative responses were detectable at 10 days posttransplant, and by 8 months post-transplant functional T- and B-cell reconstitution was documented by normal responses to mitogens and normal levels of serum immunoglobulins as well as in vitro and in vivo T-cell reactivity to specific antigens and production of specific antibody to T cell-dependent antigens in vivo. Phytohemagglutinin-induced interleukin-2 production and cell surface interleukin-2 receptor expression improved posttransplant, with normal production values observed by 8 months posttransplant. Histologic examination of appendix and thoracic lymph node obtained 9 and 17 months posttransplant, respectively, revealed near-normal lymphoid architecture, with germinal center formation providing morphologic confirmation of reconstitution. Stable split lymphoid chimerism with T cells of donor origin and B cells remaining recipient in origin was documented by sex chromosome analysis. Two years posttransplant the subject remains free of serious infections. In conclusion, this case indicates that bone marrow transplantation can produce peripheral immunoreconstitution without need for significant thymic influence, most likely by providing a source of postthymic T cells, and that bone marrow transplantation should be considered a therapeutic option in patients with DiGeorge syndrome associated with severe T-cell deficiency.
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PMID:Successful bone marrow transplantation with split lymphoid chimerism in DiGeorge syndrome. 262 Dec 43

A boy with combined immunodeficiency having low natural killer (NK)-cell activity received thymopoietin pentapeptide (TP-5) treatment, transplanted with T cell-depleted HLA-haploidentical bone marrow (BMT) cells from his father and with thymus tissue from an infant at different times during the first year of life. He showed a marked increase in large granular lymphocytes (LGL) both during the treatment with TP-5 and after BMT. The LGL generated following TP-5 injection had a T3+Leu11- surface phenotype and low NK activity. In contrast, the LGL appearing after BMT showed T3-, Leu7+, and/or Leu11+ surface phenotypes, had high NK- and K-cell activities, and were lymphokine-activated killer (LAK)-cell precursors. These killer activities were assigned to the Leu7-Leu11+ subset and proved to be of recipient origin. LGL proliferation following BMT was accompanied by neutropenia, which was improved in association with a reduction in the number of LGL and the appearance of T cells of BMT donor origin following thymus transplantation. This suggested the inhibition of granulopoiesis by the LGL and an in vitro study revealed that the Leu7+Leu11- subset of LGL suppressed the growth of granulocyte/macrophage colony-forming units. These results indicated that phenotypically different LGL could be generated by different treatments and that the LGL showing NK activity were distinct from those regulating granulopoiesis. It was also suggested that the generation of LGL was controlled by T cells.
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PMID:Phenotypical and functional heterogeneity of the large granular lymphocytes increased after various treatments in a patient with combined immunodeficiency. 264 8

The treatment of choice for certain immunodeficiency syndromes and hematological disorders is bone marrow transplantation (BMT). The success of BMT is influenced by the degree of HLA compatibility between recipient and donor. However, aberrant expression of HLA sometimes makes it difficult, if not impossible, to determine the patient's HLA type by standard serological and cellular techniques. We describe here the application of new molecular biological techniques to perform high resolution HLA typing independent of HLA expression. A patient with HLA-deficient severe combined deficiency was HLA typed using in vitro amplification of the HLA genes and sequence-specific oligonucleotide probe hybridization (SSOPH). Two major advances provided by this technology are:detection of HLA polymorphism at the level of single amino acid differences; and elimination of a requirement for HLA expression. Although the patient's lymphocytes lacked class II HLA proteins, polymorphism associated with DR7,w53;DQw2;DRw11a (a split of DR5), w52b (a split of DRw52);DQw7 were identified. The patient's class I expression was partially defective, and typing was accomplished by a combination of serological (HLA-A and -C) and SSOPH analysis (HLA-B). Complete patient haplotypes were predicted after typing of family members [A2;B35(w6); Cw4; DRw11a(w52b);DQw7 and A2;B13(w4); Cw6;DR7(w53); DQw2]. Potential unrelated donors were typed and a donor was selected for BMT.
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PMID:HLA gene amplification and hybridization analysis of polymorphism. HLA matching for bone marrow transplantation of a patient with HLA-deficient severe combined immunodeficiency syndrome. 266 36

During the last 25 years the concept of a chronic autoimmune process leading to the development of insulin dependent diabetes (IDD) has emerged. The presence of two animal models for IDD, the BB rat and the NOD mouse, has improved our ability to understand the process leading to beta cell destruction. The hallmark of an autoimmune disease is the characteristic pathologic lesion of mononuclear infiltration of the pancreatic islets. Further histologic studies of the diabetic pancreas have identified the type of cells infiltrating the islets and led to the concept of pancreatic beta cells capable of presenting antigen. The initial description of linkage disequilibrium of HLA DR3 and DR4 alleles with IDD has now progressed to the molecular level with the identification of residue 57 of the HLA DQ beta chain as crucial to the genetic predisposition to IDD. Autoantibodies to cytoplasmic antigens (ICA), surface antigens, or a membrane protein of 64 kDa identified by immunoprecipitation, autoantibodies to secreted products such as insulin and proinsulin, and autoantibodies that are cytotoxic to cultured beta cells are islet specific autoantibodies that have been described. Some are probably only markers of immunologic activity; others might participate in the destruction itself. The use of ICA as a screening tool has been successful in identifying individuals prior to the onset of IDD. Widespread cellular immunological defects have been identified both in animal models and in man. In the BB rat, a seeming paradox of severe immunodeficiency occurs in an animal with autoaggressive destruction of beta cells. More subtle defects in immunoregulation have been described in the NOD mouse and in human IDD. The response of IDD in both animal models and in man to immunomodulation and to immunosuppression offers further evidence of an immunologically mediated disease. However, some therapies in the animal models, not typically considered immunologic, such as protein restriction and insulin therapy, have prevented IDD. The possibility of intervening prior to the onset of clinical disease at the level either of the initial process of recognition of the pancreatic beta cell as a target organ or of the effector mechanism is approaching a reality in human IDD.
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PMID:Insulin dependent diabetes mellitus, an autoimmune disorder? 267 79

The human immunodeficiency virus type 1 (HIV-1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV-specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV-infected lymphoblasts. Furthermore, CTL specific for HIV envelope glycoprotein gp160 have been obtained in mice by immunization with recombinant vaccinia virus (VV) that carry the HIV env gene. In this study, we show that mice also produce strong CTL responses to gag and nef proteins following immunization with VV recombinants, thus providing a convenient model system to study T lymphocyte immunity to defined HIV antigens. To determine the specificity of circulating HIV-immune CTL in humans, a panel of doubly transfected mouse P815 tumor cells was produced which express the human HLA-A2 or HLA-A3 transplantation antigen gene and one HIV-1 gene (env, gag or nef). Using these cells as targets to CTL, we show that HIV-infected humans carry co-existing CTL sub-populations of different specificities. Each subpopulation appears to vary in intensity among different individuals. Surprisingly, CTL specific for regulatory, non-structural nef protein appear to be a major constituent of the human immune response to HIV.
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PMID:Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice. 267 60

A toddler with common variable hypoimmunoglobulinemia (CVH), inflammatory bowel disease, and recurrent Pneumocystis carinii pneumonia (PCP) on intravenous gammaglobulin (IVIG) replacement was evaluated for a combined cellular immunodeficiency. He had a normal number of circulating T-cells, natural killer (NK) cells, T-cell subset percentages, and his peripheral blood mononuclear (PBM)-derived B-cell number was low. PBM mitogen blastogenesis and mixed lymphocyte reaction (MLR) were normal. MLR activated T-cells expressed class I and II MHC antigens, interleukin 2 (IL-2), and B-cell growth factor (IL-5)-related receptors. The patient's T-cells induced control B-cell maturation with pokeweed mitogen (PWM-PC), and did not suppress PWM-PC production by allogeneic PBM. Bone marrow (BM) CD19+ B-cell number varied between 10 and 44% of all PBM, and the BM B-cell-enriched fraction failed to differentiate to PWM-PC with autologous or allogeneic T-cell help. The NK activity assayed using K562 target cells was deficient, 9.2 x 7.7% (6.9-9.2%) pt, control 35.9 x 35.8% (16.3-67.2% +/- 12.8). In the presence of interferon-alpha, 800 U/ml, the patient's NK activity increased to 17.2 x 14.9% (12.6-17.2%), control 35.9 x 51.0% (36.5-72.3% +/- 12.0). The patient's cell-mediated lympholysis of HLA nonidentical, allogeneic stimulators was normal. Maintaining trough serum IgG levels above 500 mg/dl was required to suppress recurrent PCP. This functional NK deficiency may be relevant to the development of recurrent PCP in IVIG-treated CVH patients.
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PMID:Common variable hypogammaglobulinemia, recurrent Pneumocystis carinii pneumonia on intravenous gamma-globulin therapy, and natural killer deficiency. 278 54

A 55-year-old woman with common variable immunodeficiency and mild chronic obstructive lung disease received 3 units of plasma as immunoglobulin replacement therapy. During the administration of the final unit, her temperature rose 1 degree C, with no other observable symptoms. Fifteen minutes later she developed shortness of breath without nausea, vomiting, rash, or pruritus. In 30 min she lost consciousness, was breathless, and cyanotic. Resuscitative efforts failed. Autopsy failed to pinpoint a cause of death. There was no evidence of ABO or Rh incompatibility, bacterial contamination, or hemolysis. There were no neutrophil, platelet or IgA antibodies detectable in the patient or the 3 plasma donors. There were no lymphocytotoxic HLA antibodies in the patient or two of the plasma donors. The third donor had HLA-B35 lymphocytotoxic antibodies that did not agglutinate or aggregate neutrophils. The patient's HLA type was A2, A3; B35, B40. Lymphocytotoxic crossmatches using lymphocytes of the patient were positive with plasma from the third donor but negative with the other two. An eluate prepared from post-mortem lung parenchymal tissue was cytotoxic to 7 of 8 panel lymphocytes positive for the HLA-B35 antigen but not with cells lacking B35. The implicated plasma donor was healthy with a history of 6 pregnancies. This case report illustrates the potential hazard of transfusion of plasma containing HLA antibodies.
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PMID:Fatal pulmonary transfusion reaction to plasma containing donor HLA antibody. 280 Apr 69


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