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 significance of detection of human immunodeficiency virus (HIV) DNA by the polymerase chain reaction (PCR) in seronegative or seroconverting (SC) subjects remains controversial. In a previously reported study, we identified a case in which a specimen collected 12 months before seroconversion (pre-SC) was found repeatedly to be PCR positive in three experienced laboratories, while the 6-month pre-SC bleed was PCR-negative; PCR-based human leukocyte antigen (HLA)-DQA and -DRB typing of serial peripheral blood mononuclear cell (PBMC) samples from this case did not indicate a specimen mix-up or labeling error. To further investigate this case, we used HIV env sequence and DNA heteroduplex gel-shift analyses to characterize HIV quasispecies present in serial pre- and post-SC specimens. HIV env sequences and gel-shift pattern analyses from the 12-month pre-SC versus post-SC samples indicated that markedly distinct quasispecies were present, suggesting possible abortive infection followed by reinfection and subsequent seroconversion. However, the HIV burden of this pre-SC sample was very low (1 provirus/10(6) PBMCs), and the quasispecies was highly heterogeneous, findings suggesting long-term rather than recent HIV infection. To test the hypothesis that the index pre-SC sample was PCR positive owing to trace blood contamination during initial processing, we analyzed the three seropositive samples collected on the same date in 1985. One of these samples was highly related to the index pre-SC sample by env sequence and gel-shift methodologies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of low-level contamination of blood as basis for detection of human immunodeficiency virus (HIV) DNA in anti-HIV-negative specimens. 802 18

High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma.
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PMID:Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. 820 68

Major histocompatibility complex class II deficiency (bare lymphocyte syndrome) is a rare primary immunodeficiency disorder characterized by profound defects in human leukocyte antigen class II expression, inconsistent and incomplete expression of human leukocyte antigen class I molecules, and a complete lack of cellular and humoral immune responses to foreign antigens. To define the clinical and immunologic characteristics, outcome, and natural history of major histocompatibility complex class II deficiency, we retrospectively analyzed 30 consecutive patients. Clinical onset occurred in the first year of life, usually involving recurrent bronchopulmonary infections and chronic diarrhea. The clinical course was complicated by viral meningoencephalitis, hepatitis, cholangitis, and various autoimmune phenomena. Prognosis was very poor: the mean age at the time of death was 4 years. The main cause of death was overwhelming viral infection. Recent advances in bone marrow transplantation have raised hopes of curative treatment: 6 of 14 patients who underwent bone marrow transplantation were cured. Long-term survival after human leukocyte antigen-identical and haploidentical bone marrow transplantation seemed to depend primarily on the presence of preexisting viral infections.
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PMID:Major histocompatibility complex class II deficiency: clinical manifestations, immunologic features, and outcome. 822 25

Molecular mimicry is the origin of common structural patterns in sequences of viral and host proteins, and it appears to be related to the development of autoimmune diseases. The identification of structural molecular similarities among viral and host proteins is thus very relevant in the development of engineered antiviral vaccines to avoid potentially dangerous effects. In this respect identifying pairs of similar oligopeptides between given proteins, independently of the overall degree of similarity of their amino acid sequences, is of interest. To this aim we have designed and implemented an algorithm capable of finding and classifying (with respect to their statistical significance) all possible pairs of similar oligopeptides between two proteins irrespective of length, number, location and ordering of the pairs along the sequences. The algorithm is very efficient and much more suited for this kind of local search than standard alignment programs. The latter, dealing with the sequences as a whole, are, in these cases, of very limited applicability. We have used the algorithm to compare a glycoprotein of the human immunodeficiency virus (HIV) type 1 and with the beta-chains of human leukocyte antigen (HLA). Besides a previously identified peptide, we have found a new peptide located in the fusion site of HIV that shares high similarity with the transmembrane domains of HLA.
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PMID:An algorithm for the identification of similar oligopeptides between amino acid sequences. 843 75

Primary pulmonary hypertension (PPH) may have an autoimmune basis that is influenced by host immunogenetics. The pathogenesis of primary pulmonary hypertension in human immunodeficiency virus (HIV) infection is unclear. The objective of this study was to determine whether patients with PPH and HIV infection have distinctive immunogenetic profiles. Ten racially mixed HIV-infected patients with PPH were typed for human leukocyte antigen (HLA) class II (DRB1, 3, 4, 5 and DQB1) by DNA-PCR sequence-specific oligonucleotide probes. Results were compared with two control groups: 128 HIV-negative Caucasians and a previously reported group of 97 HIV-positive, racially mixed control subjects. In those with PPH, there was a significantly increased frequency of HLA-DR6 (-DRB1*1301/2 subtypes) and of HLA-DR52 (DRB3*0301 subtype). These findings suggest that HIV-associated PPH reflects a host response to HIV-1 determined by one or more HLA-DR alleles located within the major histocompatibility complex. The same HLA-DR6 subtype found at increased frequency in our patients has previously been associated with the development of a CD8 lymphocytic host response to HIV-1, termed diffuse infiltrative lymphocytosis syndrome (DILS), which resembles autoimmune Sjogren's disease and is associated with prolonged survival. Together, these findings suggest that HIV-positive PPH may represent a clinical outcome that has similarities with that resulting from the immunogenetically determined host response present in DILS.
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PMID:Primary pulmonary hypertension in HIV infection: an outcome determined by particular HLA class II alleles. 861 57

Renal transplantation continues to be the goal of therapy for children with end-stage renal disease. Patient age, primary renal disease, psychosocial status, living versus cadaver donor allograft, optimal immunosuppressive therapy, urologic status, and maximization of growth and development must be considered in determining the optimal time for transplantation. Immunizations should be up to date, and the immune status of both the donor and the recipient with regard to Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, and hepatitis A, B, and C must be known. Prednisone, imuran, cyclosporine, and T cell antibodies remain the mainstay of immunosuppression. However, new therapies, such as FK-506, rapamycin, mofetil, brequinar, leflunomide, and human leukocyte antigen-derived peptides, are under investigation for use in transplantation. Complications, including infection, rejection, and malignancy, continue to be problematic in pediatric renal transplantation. Although patient and graft survival has improved over time, outcomes in pediatric renal transplantation continue to lag behind those in young adults.
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PMID:Progress in renal transplantation for children. 862 Mar 69

Primary human immunodeficiency virus (HIV) infection is characterized by a high-titer viremia that declines precipitously within weeks, most likely as a result of host immune responses. Peripheral blood mononuclear cells (PBMCs) and plasma of four recently HIV-infected individuals were examined to assess the humoral and cellular immune responses potentially involved in early suppression of viral replication. Neutralizing antibodies against autologous viral isolates were low or undetectable in three subjects studied. Cellular cytotoxicity was assayed using Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (B-LCLs) infected with recombinant vaccinia that express HIV-1 proteins. HIV envelope-specific cytotoxicity, which was not mediated by CD8+ cells nor human leukocyte antigen (HLA) class I restricted, developed in PBMCs of all four subjects early after primary infection, but was not correlated with declines in viremia. Gag-specific cytotoxic T lymphocyte (CTL) activity was observed in freshly isolated PBMCs of two subjects, and HIV-specific CTL cell lines were cultured from PBMCs of three subjects shortly after HIV infection. Antibody-dependent cellular cytotoxicity (ADCC) developed early in all four subjects, and was temporally correlated with declines in viremia in two subjects in whom viral load was well characterized. These data suggest that both CTL responses and ADCC may be critical to control of viral replication in acute HIV infection.
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PMID:HIV-specific cellular and humoral immune responses in primary HIV infection. 884 17

Despite the fact that nucleoside analogues, such as aciclovir and ganciclovir, and DNA-polymerase inhibitors, such as foscarnet, have a proven antiviral effect on oropharyngeal-Epstein-Barr virus (EBV) replication, they have been unable to show any effect on the severity or duration of infectious mononucleosis (IM), a condition for which there is currently no established treatment. Clinical symptoms may be due to an EBV-induced polyclonal humoral, as well as cellular, immunoreactivity with limited pathology caused by viral replication itself. However, despite an extensive immune response, 90% of tested IM patients (n = 36) had a spontaneous outgrowth of in vivo EBV-infected B-lymphocytes at onset of disease, indicating lack of specific EBV-restricted cellular cytotoxicity at this time. Establishment of an EBV-specific T-lymphocyte response occurred 90-180 days after onset of disease (human leukocyte antigen-restricted cytotoxicity against EBV-infected B-cells). Thus, development of a specific cytotoxic response was a gradual and slow process. Assessment of cytokine pattern, at the single cell level, was performed by immunocytochemical technique and by enzyme-linked immunosorbent assay. This revealed an increased production of interleukin (IL)-2, interferon (IFN)-gamma, IL-6 and tumour necrosis factor (TNF) beta in all IM patients. Those with disseminated disease were characterized by lack of IFN-gamma production. This loss was selective since in vitro stimulation with superantigen, such as streptococcal pyrogenic exotoxin A, induced a normal response. These patients lacked signs of EBV-specific T-cell cytotoxicity in vitro. Treatment with intravenous or subcutaneous IFN-gamma, 1.5 MU every second day, in combination with intravenous immunoglobulin G (0.5 g/kg three times per week) and oral aciclovir, 800 mg 5 times daily, has shown promising results in some patients. Cytokine production in tonsil tissue in 4 patients with fulminant IM and respiratory tract obstruction showed a concomitant expression of IL-2, IFN-gamma, IL-6, TNF beta, transforming growth factor (TGF) beta 1-3, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-4 IL-1alpha, IL-beta and TNF alpha. The number of IL-2, IFN-gamma, IL-6 and TNF beta producing cells was significantly higher compared to tonsil tissue obtained from children with tonsillar hypertrophy. Thus, IM is associated with extensive local cytokine production. It is suggested that this extensive cytokine production is closely involved in the pathology of IM and that patients with atypical IM have a dysregulation in the cytokine network. However, the mechanism by which EBV-infected B-lymphocytes triggers this cytokine cascade is still unknown. These findings show the need for evaluation of patients with immunodeficiency and EBV-induced lymphoproliferative disorders and perhaps the introduction of new immunoregulatory treatment strategies.
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PMID:Clinical and immunological considerations in Epstein-Barr virus-associated diseases. 886 Mar 57

CD8+ T lymphocytes may mediate important host responses to human immunodeficiency virus (HIV) infection by human leukocyte antigen (HLA)-restricted cytotoxicity and production of soluble HIV suppressor factors. CD8+ lymphocytes are also important for the suppression of many latent pathogens responsible for opportunistic disease in HIV-infected patients. There has been no systematic analysis of the responses of CD8+ lymphocyte counts to antiretroviral therapy. We compared CD8+ lymphocyte responses in seven trials of nucleoside or non-nucleoside analog reverse transcriptase inhibitors and in two trials of ritonavir, a HIV protease inhibitor. Nucleoside analog and non-nucleoside analog reverse transcriptase inhibitor monotherapy resulted in no substantial changes in CD8+ counts relative to baseline or placebo. Combination nucleoside analog therapy resulted in variable peak responses (-145 to +240 cells/mm3), which remained significantly above baseline for 0 to 12 weeks. In contrast, ritonavir monotherapy caused a peak increase of 892 CD8+ cells/mm3, which remained significantly above baseline for 32 weeks. There was a significant correlation (Rs 0.61, p = 0.01) between the peak CD4+ cell and CD8+ responses to each therapy, but no significant correlation between the peak viral load responses and peak CD8+ cell responses. These findings suggest that the greater CD8+ response seen with ritonavir may be due to its specific inhibition of HIV protease and also that the CD8+ response is dependent on new CD4+ cell production. The CD8+ lymphocyte proliferation observed with protease inhibitor therapy could result in improved suppression of HIV replication by the immune system and should be confirmed in a prospective trial comparing protease inhibitors with both nucleoside and non-nucleoside analog therapies.
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PMID:CD8+ lymphocyte responses to antiretroviral therapy of HIV infection. 970 47

It has been proposed that the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope gp120 carboxy-terminal sequence, TKAKRRVVEREKR (CT120), may represent a functional mimic of the human leukocyte antigen (HLA) class II DR beta-chain third hypervariable region (HVR3) sequence motif located at position 69-81. Presentation of this potentially pathogenic fragment by HLA class I and/or II molecules, in a manner analogous to the indirect pathway of allorecognition, may induce both widespread cellular activation and also break self-tolerance, resulting in the selective and progressive anti-self HLA class II-directed immune suppression, which is a central feature of HIV-1 infection and the associated acquired immune deficiency syndrome (AIDS). To investigate the functional role of the HIV-1 gp120 C-terminal fragment T cell lines (TCLs) were raised from three healthy HIV-1-seronegative subjects at low risk of HIV-1 exposure, by repeated stimulation with a short synthetic 13-mer CT120 peptide in vitro. Graded concentrations (10[3] to 5 x 10[4]) of CT120 TCLs suppressed the primary 6-day proliferation of autologous PBMCs in response to the soluble antigens tetanus toxoid (TT) and purified protein derivative (PPD). In contrast, CT120 TCLs demonstrated no suppressive effect on 3-day phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM) mitogenic responses. Fractionation of CT120 TCLs into highly purified CD4+ and CD8+ T cell subsets demonstrated that the CD8+ T cell fraction mediated the suppressor effector function. HLA restriction analysis revealed a complex pattern as both anti-HLA class II DR and anti-HLA class I (A, B, C) MAbs inhibited proliferation of oligoclonal CD8+ CT120 TCLs. Strategies aimed at specifically inhibiting such putative immunopathogenic HIV-1-encoded T cell epitopes may be an important consideration for development of future HIV-1 immunotherapy.
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PMID:HIV type 1 envelope glycoprotein 120 carboxy-terminal peptide-induced human T cell lines selectively suppress heterogeneous proliferative T cell responses to soluble antigens. 933 48


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