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)

To evaluate whether host genotype influences disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1), molecular techniques were used to determine genotypes at immune response loci for 114 HIV-1-infected homosexual/bisexual white men in the San Francisco Men's Health Study. Candidate genes evaluated were HLA-DQA1 and -DRB1, complement C4A and C4B, alpha- and beta-interferons, and the heavy chain of immunoglobulin gamma 1. Of the 114 men, 29 were asymptomatic, 21 were symptomatic men and AIDS patients (p = 0.02). Specifically, the HLA haplotype DRB1*0702-DQA1*0201 was associated with absence of symptoms (p = 0.003). Conversely, the frequency of the complement C4B-L allele was higher among patients with symptoms or with AIDS than among asymptomatic subjects (p = 0.02). These results suggest that genes in or near the major histocompatibility complex may influence the rate of disease progression among HIV-1-infected men.
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PMID:Influence of host genotype on progression to AIDS among HIV-infected men. 185 93

IgA deficiency (IgA-D) represents the most common immunodeficiency syndrome of infancy. In most cases IgA-D represents an isolated immunological disorder, while sometimes it is associated with IgG subclass deficiency or with the presence of autoantibodies. We investigated the pattern of association of IgA-D with DRB1 and DQB1 loci of the HLA region by DNA molecular typing, which allows the identification of previously serologically undefined specificities. We also compared the gene frequency of DRB1 and DQB1 allelic variants between IgA-D subjects with or without serum autoantibodies. Our results indicate that the gene frequency of the DRB1*0102 subtype and of the DRB1*0102, DQB1*0501 haplotype is significantly higher in IgA-D than in the general population. Furthermore, the IgA-D subjects with autoantibodies showed a positive association with DR4 and DR13 subtypes, thus supporting the hypothesis that genetic factors are also involved in the association between IgA-D and autoantibodies.
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PMID:DNA typing of DQ and DR alleles in IgA-deficient subjects. 858 46

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

Transmission of human immunodeficiency virus 1 (HIV-1) from an infected women to her offspring during gestation and delivery was found to be influenced by the infant's major histocompatibility complex class II DRB1 alleles. Forty-six HIV-infected infants and 63 seroreverting infants, born with passively acquired anti-HIV antibodies but not becoming detectably infected, were typed by an automated nucleotide-sequence-based technique that uses low-resolution PCR to select either the simpler Taq or the more demanding T7 sequencing chemistry. One or more DR13 alleles, including DRB1*1301, 1302, and 1303, were found in 31.7% of seroreverting infants and 15.2% of those becoming HIV-infected [OR (odds ratio) = 2.6 (95% confidence interval 1.0-6.8); P = 0.048]. This association was influenced by ethnicity, being seen more strongly among the 80 Black and Hispanic children [OR = 4.3 (1.2-16.4); P = 0.023], with the most pronounced effect among Black infants where 7 of 24 seroreverters inherited these alleles with none among 12 HIV-infected infants (Haldane OR = 12.3; P = 0.037). The previously recognized association of DR13 alleles with some situations of long-term nonprogression of HIV suggests that similar mechanisms may regulate both the occurrence of infection and disease progression after infection. Upon examining for residual associations, only only the DR2 allele DRB1*1501 was associated with seroreversion in Caucasoid infants (OR = 24; P = 0.004). Among Caucasoids the DRB1*03011 allele was positively associated with the occurrence of HIV infection (P = 0.03).
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PMID:Major histocompatibility complex class II DR alleles DRB1*1501 and those encoding HLA-DR13 are preferentially associated with a diminution in maternally transmitted human immunodeficiency virus 1 infection in different ethnic groups: determination by an automated sequence-based typing method. 861 4

In a previous study, we reported the existence of a specific anergy affecting selectively the V beta 8 subset in both CD4 and CD8 T cells from human immunodeficiency virus (HIV)-infected persons. Because this observation gives evidence for a previous in vivo activation of this subset by a superantigen, we further characterize, in the present study, this V beta 8-anergy associated with HIV infection. Molecular T cell receptor analysis indicates that the V beta 8-anergized T cells are polyclonal. Furthermore, we show the dependence of this anergy on the expression of allelic forms of HLA class II DRB1 molecules. These observations explain the frequency of anergic persons among HIV-infected donors (56%) and are consistent with a previous in vivo superantigenic activity. Comparative analyses of disease evolution between V beta 8 responder and anergic persons do not show any clear relation between the V beta 8 status and acquired immunodeficiency syndrome pathogenesis. However, the stability of the V beta 8 status, the absence of correlation with previous microbial infections, and the previously reported precocity of V beta 8 anergization are in favor of a strong association between the in vivo existence of a V beta 8-specific superantigen and HIV infection. Finally, the functional dichotomy we observe for all anergized donors between blood and lymph node T cells raises the question of the in vivo localization of the superantigenic activity.
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PMID:Evidence for an in vivo superantigenic activity in human immunodeficiency virus-infected individuals. 882 35

Selective immunoglobulin A (IgA) deficiency, the most common form of primary immunodeficiency, is related to the HLA genes. Previous studies demonstrated associations with particular HLA-DR-DQ haplotypes and a neutral amino acid at position 57 of the DQbeta chain was implicated in the susceptibility to selective IgA deficiency. In this study we reanalyzed the reported findings by high-resolution DNA typing of the loci DRB1, DQB1 and DQA1. We compared the typing results of 74 IgA-deficient individuals, detected by screening of blood donors, with those taken from 111 healthy controls. Results confirmed a strong positive association with DRB1*0301, DQB1*02 and a negative association with DRB1*1501, DQB1*0602. Considering the molecular interactions between HLA class II alleles and the peptides bound we conclude that the amino acid at position 57 of the DQbeta chain may contribute to the susceptibility to selective IgA deficiency, but not determine it. An extended statistical analysis strengthened the hypothesis that selective IgA deficiency might be communicated by the distinct haplotype DRB1*0301, DQB1*02.
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PMID:High-resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB1*0301, DQB1*02 haplotypes. 938 25

Umbilical cord blood (UCB) is being increasingly used for hematopoietic stem cell transplantation and has been associated with a reduced incidence of severe graft-versus-host disease (GVHD). To further investigate the relative merits of unrelated donor UCB versus bone marrow (BM), a matched-pair analysis comparing the outcomes of recipients of 0 to 3 human leukocyte antigen (HLA)-mismatched UCB and HLA-A, B, DRB1-matched BM was performed. UCB patients, who received cyclosporine (CSA) and methylprednisolone (MP), were matched for age, diagnosis, and disease stage with BM patients, who received either methotrexate (MTX) and CSA (26 pairs) or T-cell depletion (TCD) and CSA/MP (31 pairs). Patients were predominantly children (median age, 5 years) undergoing transplantation for malignancy, storage diseases, BM failure, and immunodeficiency syndromes between 1991 and 1999. Although neutrophil recovery was significantly slower after UCB transplantation, the probability of donor-derived engraftment at day 45 was 88% in UCB versus 96% in BM-MTX recipients (P =.41) and 85% in UCB versus 90% in BM-TCD recipients (P =.32), respectively. Platelet recovery was similar in UCB versus BM pairs. Furthermore, incidences of acute and chronic GVHD were similar in UCB and BM recipients, with 53% of UCB versus 41% of BM-MTX recipients alive (P =.40) and 52% of UCB versus 56% of BM-TCD recipients alive at 2 years (P >.80), respectively. These data suggest that despite increased HLA disparity, probabilities of engraftment, GVHD, and survival after UCB transplantation are comparable to those observed after HLA-matched BM transplantation. Therefore, UCB should be considered an acceptable alternative to HLA-matched BM for pediatric patients.
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PMID:Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. 1134 17

Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.
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PMID:Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients show a different profile of major histocompatibility complex class II alleles. 1555 90

Polymorphisms of genes in the human leukocyte antigen (HLA) complex, particularly those encoding HLA-DR, have been suggested as markers of susceptibility to Kaposi's sarcoma (KS). We conducted a case-control study comparing 147 homosexual men who developed KS after infection by human immunodeficiency virus-1 (HIV-1) and human herpes virus 8 (HHV8) with 147 matched dually infected men without HIV-associated KS (HIV-KS) from the Multicenter AIDS Cohort Study. HLA-B, DRB1, DRB3, DRB4, DRB5, and DQB1 polymorphisms were examined by high-resolution DNA-based methods. Differences in distributions of genetic variants were tested by conditional logistic regression. Previously reported relationships with HLA-DRB1 alleles could not be confirmed. Instead, other associations were observed. In univariate analysis, KS was weakly associated with B*2702/5 (odds ratio (OR)=0.40, 95% confidence interval (CI)=0.18-0.91). Similar or stronger associations, positive or negative, were seen for haplotypes containing class II alleles: DRB1*1302-DQB1*0604 (OR=3.67, 95% CI=1.02-13.1), DRB4 (DR53) haplotype family members [OR=0.52, 95% CI=0.32-0.85], and DRB3 (DR52) haplotype family members (OR=1.69, 95% CI=1.07-2.67). The B*1402-DRB1*0102 haplotype, which invariably contains the V281L mutation in the 21-hydroxylase gene governing adrenal steroid biosynthesis, occurred in five cases and one control (OR=5.0, 95% CI=0.58-42.8). In a final multivariable analysis, only DRB1*1302-DQB1*0604 (OR=6.43, 95% CI=1.28-32.3, P=0.02) remained significantly associated with KS. Associations of HLA-DRB families with HIV-KS could reflect underlying immune dysregulation. The HLA B*1402-DRB1*0102 haplotype associated with increased risk of KS might represent an antigen-presenting pathway unfavorable for immune response to HHV8. Alternatively, the relationship might hold a clue to the predilection of KS for men because that haplotype harbors the mutant form of the 21-hydroxylase gene.
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PMID:HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma. 1590 98

Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Botswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Botswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.
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PMID:Major histocompatibility complex class II (HLA-DRB and -DQB) allele frequencies in Botswana: association with human immunodeficiency virus type 1 infection. 1614 66


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