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 factors governing interindividual variability in disease progression among children vertically infected with human immunodeficiency virus type 1 (HIV-1) remain unclear. Because it has recently been shown in infected adults that the density of CC chemokine receptor 5 (CCR5) molecules at the surface of nonactivated (human leukocyte antigen [HLA]-DR(-)) CD4+ T cells correlates with disease progression, the same correlation was sought in children. HLA-DR(-)CD4+ T cell surface CCR5 density was constant over time and correlated with the bioclinical stage and with the CD4 cell slope observed before antiretroviral treatment. In addition, CCR5 density was negatively correlated with the intensity of the decrease in viremia during antiretroviral therapy and was positively correlated with CD4 cell slope since birth. These results are compatible with the hypothesis that CCR5 density is a key factor governing disease progression in pediatric HIV-1 infection and, thereby, an indicator of prognosis. Moreover, they suggest that therapies aimed at reducing CCR5 accessibility should slow down HIV disease evolution in children.
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PMID:Response to treatment and disease progression linked to CD4+ T cell surface CC chemokine receptor 5 density in human immunodeficiency virus type 1 vertical infection. 1193 Mar 15

Host human leukocyte antigens (HLAs) integrated into the human immunodeficiency virus (HIV) type 1 envelope could theoretically determine, as in tissue transplants, whether HIV-1 is "rejected" by exposed susceptible persons, preventing transmission. HLA discordance (mismatch) was examined among 45 heterosexual partner pairs in which at least 1 partner was HIV-1 infected and exposure or transmission between partners had occurred. Immunologic discordance at class II HLA-DRB3 (present in the HIV donor partner but absent in the recipient partner) was associated with lack of transmission of HIV-1. Eight (35%) of 23 partner pairs in which HIV-1 transmission did not occur were immunologically discordant at HLA-DRB3, compared with 0 of 11 partner pairs in which HIV-1 transmission did occur (P=.027). Further investigation of the roles of class II HLAs in HIV-1 transmission and as possible components of HIV-1 vaccines should be pursued.
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PMID:Discordance at human leukocyte antigen-DRB3 and protection from human immunodeficiency virus type 1 transmission. 1208 18

Natural killer (NK) cells provide defense in the early stages of the innate immune response against viral infections by producing cytokines and causing cytotoxicity. The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes. Here we report that the activating KIR allele KIR3DS1, in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed progression to AIDS in individuals infected with human immunodeficiency virus type 1 (HIV-1). In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations are strongly suggestive of a model involving an epistatic interaction between the two loci. The strongest synergistic effect of these loci was on progression to depletion of CD4(+) T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection.
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PMID:Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. 1213 47

The study of the immunologic response to whole human immunodeficiency virus type 1 (HIV-1) antigen is limited by the presence of highly immunogenic human leukocyte antigen (HLA) alloantigens on the envelope of wild type virus. This paper outlines the production of HIV-1 infectious virions free of HLA for use as whole viral antigens in immunoassays. An infectious molecular clone of HIV-1 was transfected into the K-562 cell line, which does not express HLA on the cell surface. After a 30-day selection period, to ensure stable transfection, cells and culture supernatants were analyzed for productive HIV-1 infection and virion infectivity. An enzyme-linked immunosorbent assay (ELISA) confirmed the presence of p24 in the culture supernatants. Molecular confirmation of HIV-1 transfection was achieved by gene amplification. Flow cytometric analysis was used to identify gp120 on the surface of the infected cells. Viral supernatants were tested for HIV infectivity in peripheral blood mononuclear cells (PBMCs). The usefulness of this viral preparation as whole virus antigens was validated using PBMCs from HIV-infected individuals. These results indicate the successful production of HIV-1 infectious virions, which do not have HLA molecules on their viral envelope, and demonstrate their utility for immunoassays.
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PMID:Development of a novel allo-independent HIV-1 virus preparation for use in immunoassays. 1219 11

Kidney transplantation should be strongly considered for all medically suitable patients with chronic and end-stage renal disease (ESRD). Improvements in outcomes after renal transplantation have resulted in a more liberal selection of patients. High-risk category patients including human immunodeficiency virus (HIV)-positive, highly sensitized patients, T-cell positive cross-match, and ABO blood group-incompatible patients are now considered potential renal transplant candidates. Unfortunately, the demand for kidney transplants far exceeds the supply of available organs, causing a persistent increase in the number of patients on the waiting list with a parallel increase in the waiting time for a cadaveric kidney transplant. This has 2 major consequences. First, patients on the waiting list are getting sicker and older. Second, living donors have assumed increasing importance in renal transplantation. Pre-existing morbidities including malignancies, cardiovascular disease, infections, and coagulopathies should be extensively evaluated before proceeding to transplantation. Special attention should be given to cardiovascular risk factors because the leading cause of death after renal transplant is cardiovascular disease. A full immunologic evaluation with ABO blood group determination, human leukocyte antigen (HLA) typing, screening for antibody to HLA phenotypes, and cross-matching need to be gathered before transplantation to avoid antibody-mediated hyperacute rejection or to proceed with specific protocols in highly sensitized or in positive T-cell cross-match patients. With the increased rate of donation from living donors, regular follow-up evaluation of kidney donors is recommended to detect hypertension or proteinuria in those who may develop it.
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PMID:Pretransplant evaluation of renal transplant candidates. 1243 96

To examine the relationship of human leukocyte antigen (HLA) class I and transporter associated with antigen processing (TAP) genes with resistance to human immunodeficiency virus type 1 (HIV-1) infection, 100 HIV-seronegative men who had been exposed repeatedly to HIV-1 were compared with 184 men who had seroconverted to HIV positive and had lower risk. In the univariate analysis, the HLA-A2 supertype, excluding A*0201 (HLA-A2/6802 supertype; odds ratio [OR], 4.45; 95% confidence interval [CI], 1.33-4.84; P=.009) was associated with resistance to HIV-1 infection; the effect was the result of the presence of the A*0205 subgroup alleles. Susceptibility was associated in univariate analysis with the B*35 Px alleles (OR, 0.29; 95% CI, 0.08-0.99; P=.037), which suggests that differential preferences for amino acids at the C terminus may influence peptide-binding capacity. TAP2 Ala665 was also associated with resistance (OR, 2.26; 95% CI, 1.35-3.79; P=.002), perhaps because of its higher efficiency in transporting peptides, thus eliciting a greater CD8(+) T cell response, or because of linkage disequilibrium. In multivariate logistic analysis, only the A*0205 subgroup (OR, 5.56; 95% CI, 1.34-23.10; P=.018) and the TAP2 Ala665 (OR, 2.22; 95% CI, 1.28-3.84; P=.005) were associated with resistance.
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PMID:Association of polymorphisms in human leukocyte antigen class I and transporter associated with antigen processing genes with resistance to human immunodeficiency virus type 1 infection. 1271 21

T cell dynamics and viral genotype were studied in human immunodeficiency virus 1-infected individuals receiving antiretroviral therapy who were viremic and had either increasing (discordant immunological responders) or decreasing (nonresponders) CD4(+) T cell counts. A comparison was made with treated individuals who were not viremic and had increasing CD4(+) T cell counts (complete responders). Nonresponders had higher CD4(+) T cell proliferation (as assessed by Ki67 expression) and immune activation (as assessed by CD38 and human leukocyte antigen-DR expression), together with a reduction in T cell receptor excision circles, compared with discordant immunological responders and complete responders, which suggests that there is enhanced viral pathogenicity in both peripheral T cells and the thymus. Although there was a high prevalence of mutations in the protease and reverse transcriptase genes in discordant immunological responders, these changes were also observed in nonresponders.
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PMID:Immunological and virological failure after antiretroviral therapy is associated with enhanced peripheral and thymic pathogenicity. 1279 68

Eight hemochromatosis probands with HFE C282Y homozygosity had frequent, severe, or unusual infections and common variable immunodeficiency (CVID) or immunoglobulin (Ig) G subclass deficiency (IgGSD). Thus, we performed serum Ig isotyping and other characterization of 43 additional unselected probands, 5 human leukocyte antigen (HLA)-identical siblings, and 240 consecutive CVID or IgGSD index patients. C282Y allele frequencies were estimated in 58 CVID or IgGSD index patients without hemochromatosis phenotypes and in 341 controls. HLA-A and -B haplotypes and frequencies were determined in all 51 probands, 186 CVID or IgGSD index patients without hemochromatosis phenotypes, and 751 controls. Thirteen unselected probands (30%) had CVID or IgGSD. Among all 21 hemochromatosis probands with CVID (n = 4) or IgGSD (n = 17), Ig subclass deficiency patterns were IgG(1) (n = 5), IgG(1) and IgG(3) (n = 6), IgG(3) (n = 9), and IgG(1), IgG(3), and IgG(4) (n = 1). IgG(2) or IgA deficiency was not detected; one proband had IgM deficiency. Mean values of total IgG, IgG(1), and IgG(3) were significantly lower in probands with CVID or IgGSD. Mean values of age, transferrin saturation, and ferritin at diagnosis and phlebotomy units required to induce iron depletion were similar in probands with or without CVID or IgGSD; phlebotomy had no apparent effect on IgG levels. C282Y frequencies were similar in CVID or IgGSD index cases without hemochromatosis phenotypes and in controls. There was concordance of Ig and hemochromatosis phenotypes in probands and respective HLA-identical siblings. Eight of 240 CVID or IgGSD index patients had hemochromatosis phenotypes and C282Y homozygosity (3 vs 0.7% and 0.2% controls; P < 0.0001, respectively). The frequency of A*03-B*07 was greater in CVID and IgGSD index cases without hemochromatosis phenotypes than in controls (0.0968 vs 0.0546, respectively; P = 0.0032). HLA-A*03-B*07 was the predominant haplotype in probands grouped by presence or absence of CVID or IgGSD. Some probands in each group were A*03-B*07 homozygotes; group A*03-B*07 frequencies were similar. We conclude that serum IgG abnormalities characteristic of CVID or IgGSD are common in hemochromatosis probands, and that the prevalence of hemochromatosis is increased in CVID and IgGSD index cases. These observations could be explained by the increased frequencies of HLA-A*03-B*07 in C282Y homozygotes and in CVID and IgGSD, and by the common occurrence of putative CVID or IgGSD allele(s) on haplotypes bearing C282Y.
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PMID:Common variable immunodeficiency and IgG subclass deficiency in central Alabama hemochromatosis probands homozygous for HFE C282Y. 1285 Apr 93

Three moderately to broadly recognized equine infectious anemia virus (EIAV) peptides that contained helper T-lymphocyte (Th) 1 epitopes were previously identified. Although lipopeptide immunization was only weakly immunostimulatory in a preliminary study, as measured by T-lymphocyte proliferation responses, it was of interest to define additional broadly recognized Th1 epitopes to include in future immunization trials. Using broadly cross-reactive and conserved Th epitopes known in the related human immunodeficiency virus-1 (HIV-1) and binding motifs defined in human leukocyte antigen DR molecules as guides, this work identified three new peptides containing Th1 epitopes recognized by 60-75% of EIAV infected horses. The observed similarity across species of major histocompatibility complex (MHC) class II binding motifs and the conservation of Th peptides between related viruses should allow easier targeting of Th epitope regions in less well characterized pathogens and/or in species whose MHC class II molecules are poorly defined.
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PMID:Selecting peptides to optimize Th1 responses to an equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides. 1294 8

The human leukocyte antigen (HLA)-B22 serogroup--which consists of the alleles B*54, B*55, and B*56--has been associated with rapidly progressive disease in white patients with human immunodeficiency virus (HIV) infection. Subjects from 3 cohorts of men who have sex with men (N=671), all of whom experienced HIV-1 seroconversion at roughly the same time, were molecularly typed at HLA-A, -B, and -C loci. Mean HIV RNA loads during early HIV infection were higher in B22-positive men than in B22-negative men (difference, 0.481 log(10) HIV RNA copies/mL; 95% confidence interval [CI], 0.156-0.806 log(10) HIV RNA copies/mL; P=.004). Independent of accepted markers of progression, time-to-AIDS was shorter in B22-positive seroconverters (adjusted hazard ratio, 1.98; 95% CI, 1.27-3.10; P=.003). White B22 serogroup alleles (B*55 and *56) appear to predispose to unfavorable outcome of HIV infection as strongly as some or all B*35 and B*53 alleles. This finding may have greater implications for Asians, because the marker frequency for B22 is higher among Asians than among whites (approximately 10% vs. approximately 4%).
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PMID:Influence of human leukocyte antigen-B22 alleles on the course of human immunodeficiency virus type 1 infection in 3 cohorts of white men. 1296 17


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