Richard A Kaslow

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Publications (252)2118.7 Total impact

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    ABSTRACT: In individuals with human immunodeficiency virus type 1 (HIV-1) infection, CD4:CD8 lymphocyte ratio is often recognized as a quantitative outcome that reflects the critical role of both CD4(+) and CD8(+) T-cells in HIV-1 pathogenesis or disease progression. Our work aimed to first establish the dynamics and clinical relevance of CD4:CD8 ratio in a cohort of native Africans and then to examine its association with viral and host factors, including: (i) length of infection, (ii) demographics, (iii) HIV-1 viral load (VL), (iv) change in CD4(+) T-lymphocyte count (CD4 slope), (v) HIV-1 subtype, and (vi) host genetics, especially human leukocyte antigen (HLA) variants. Data from 499 HIV-1 seroconverters with frequent (monthly to quarterly) follow-up revealed that CD4:CD8 ratio was stable in the first 3 years of infection, with a modest correlation with VL and CD4 slope. A relatively normal CD4:CD8 ratio (>1.0) in early infection was associated with a substantial delay in disease progression to severe immunodeficiency (<350 CD4 cells/μl), regardless of other correlates of HIV-1 pathogenesis (adjusted hazards ratio (HR) = 0.43, 95% confidence interval (CI) = 0.29-0.63, P < 0.0001). Low VL (<10,000 copies/ml) and HLA-A*74:01 were the main predictors of CD4:CD8 ratio >1.0, but HLA variants (e.g., HLA-B*57 and HLA-B*81) previously associated with VL and/or CD4 trajectories in eastern and southern Africans had no obvious impact on CD4:CD8 ratio. Collectively, these findings suggest that CD4:CD8 ratio is a robust measure of immunologic health with both clinical and epidemiological implications.
    Full-text · Article · Jul 2015 · Frontiers in Microbiology
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    ABSTRACT: Numerous reports have suggested that immunogenetic factors may influence human immunodeficiency virus (HIV)-1 acquisition, yet replicated findings that translate between study cohorts remain elusive. Our work aimed to test several hypotheses about genetic variants within the IL10-IL24 gene cluster that encodes interleukin (IL)-10, IL-19, IL-20 and IL-24. In aggregated data from 515 Rwandans and 762 Zambians with up to 12 years of follow-up, 190 single-nucleotide polymorphisms passed quality control procedures. When HIV-1-exposed seronegative subjects (n=486) were compared with newly seroconverted individuals (n=313) and seroprevalent subjects (n=478) who were already infected at enrollment, rs12407485 (G>A) in IL19 showed a robust association signal in adjusted logistic regression models (odds ratio=0.64, P=1.7 × 10−4 and q=0.033). Sensitivity analyses demonstrated that (i) results from both cohorts and subgroups within each cohort were highly consistent; (ii) verification of HIV-1 infection status after enrollment was critical; and (iii) supporting evidence was readily obtained from Cox proportional hazards models. Data from public databases indicate that rs12407485 is part of an enhancer element for three transcription factors. Overall, these findings suggest that molecular features at the IL19 locus may modestly alter the establishment of HIV-1 infection.
    Full-text · Article · Jan 2015 · Genes and immunity
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    Full-text · Article · Oct 2014 · AIDS Research and Human Retroviruses
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    ABSTRACT: The major histocompatibility complex (MHC) region on chromosome 6p21.3 is suspected to host susceptibility loci for HIV-related Kaposi’s sarcoma (HIV-KS). A nested case-control study in the Multicenter AIDS Cohort Study was designed to conduct fine genetic association mapping across central MHC. Individuals co-infected with HIV-1 and HHV-8 who later developed KS were defined as cases (n=354) and were matched 1:1 with co-infected KS-free controls. We report data for new independent MHC class II and III susceptibility loci. In particular, class II HLA-DMB emerged as a strong candidate, with the intronic variant rs6902982 A>G associated with a 4-fold increase of risk (OR= 4.09; 95% CI: 1.90–8.80; p= 0.0003). A striking multiplicative effect on the estimated risk was associated with further carriage of two non-synonymous variants, rs1800453 A>G (Asp697Gly) and rs4148880 A>G (Ile393Val), in the linked TAP1 gene (OR=10.5; 95% CI: 2.54–43.6; p=0.0012). The class III susceptibility variant is moderately associated with HIV-KS and lies within a 120 Kb-long haplotype (OR=1.52; 95% CI: 1.01–2.28; p=0.047) formed by rs7029 A>G (GPANK1 3’UTR), rs1065356 G>A (LY6G6C), rs3749953 A>G (MSH5-SAPCD1 readthrough) and rs707926 G>A (VARS). Our data suggest that antigen processing by MHC class II molecules is a target pathway in the pathogenesis of HIV-KS.
    Full-text · Article · Jul 2014 · Genes and Immunity
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    ABSTRACT: Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of "missing heritability" in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.
    Full-text · Article · Jun 2014 · Human Genetics
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    ABSTRACT: Objective: To evaluate the impact of mitochondrial DNA (mtDNA) haplogroups on virologic and immunological outcomes of HIV infection. Design: HAART-naive African American adolescent participants to the Reaching for Excellence in Adolescent Care and Health study. Methods: The mtDNA haplogroups were inferred from sequenced mtDNA hypervariable regions HV1 and HV2 and their predictive value on HIV outcomes were evaluated in linear mixed models, controlled for human leukocyte antigen (HLA)-B27, HLA-B57 and HLA-B35-Px alleles and other covariates. Results: We report data showing that the mtDNA L2 lineage, a group composed of L2a, L2b and L2e mtDNA haplogroups in the studied population, is significantly associated (beta = -0.08; Bonferroni-adjusted P = 0.004) with decline of CD4+ T cells (median loss of 8 +/- 1 cells per month) in HAART-naive HIV-infected individuals of African American descent (n = 133). No significant association (P < 0.05) with set-point viral load was observed with any of the tested mtDNA haplogroups. The present data concur with previous findings in the AIDS Clinical Trials Group study 384, implicating the L2 lineage with slower CD4(+) T-cell recovery after antiretroviral therapy in African Americans. Conclusions: Whereas the L2 lineage showed an association with unfavorable immunological outcomes of HIV infection, its phylogenetic divergence from J and U5a, two lineages associated with accelerated HIV progression in European Americans, raises the possibility that interactions with common nucleus-encoded variants drive HIV progression. Disentangling the effects of mitochondrial and nuclear gene variants on the outcomes of HIV infection is an important step to be taken toward a better understanding of HIV/AIDS pathogenesis and pharmacogenomics. (C) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
    No preview · Article · Jun 2014 · AIDS (London, England)
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    ABSTRACT: OBJECTIVE:: To evaluate the impact of mitochondrial DNA (mtDNA) haplogroups on virologic and immunological outcomes of HIV infection. DESIGN:: HAART-naive African American adolescent participants to the Reaching for Excellence in Adolescent Care and Health study. METHODS:: mtDNA haplogroups were inferred from sequenced mtDNA hypervariable regions HV1 and HV2 and their predictive value on HIV outcomes were evaluated in linear mixed models, controlled for human leukocyte antigen (HLA)-B27, HLA-B57 and HLA-B35-Px alleles and other covariates. RESULTS:: We report data showing that the mtDNA L2 lineage, a group composed of L2a, L2b and L2e mtDNA haplogroups in the studied population, is significantly associated (beta = -0.08; Bonferroni-adjusted P = 0.004) with decline of CD4 T cells (median loss of 8 ± 1 cells per month) in HAART-naïve HIV-infected individuals of African American descent (n = 133). No significant association (P < 0.05) with set-point viral load was observed with any of the tested mtDNA haplogroups. The present data concur with previous findings in the AIDS Clinical Trials Group study 384, implicating the L2 lineage with slower CD4 T-cell recovery after antiretroviral therapy in African Americans. CONCLUSIONS:: Whereas the present data show that the L2 lineage is associated with unfavorable immunological outcomes of HIV infection, its phylogenetic divergence from J and U5a, two lineages associated with accelerated HIV progression in European Americans, raises the possibility that interactions with common nucleus-encoded variants drive HIV progression. Disentangling the effects of mitochondrial and nuclear gene variants on the outcomes of HIV infection should be an important goal toward a better understanding of HIV/AIDS pathogenesis and pharmacogenomics.
    Full-text · Article · Jun 2014 · AIDS
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    ABSTRACT: Background KIR2DS4 gene variants encode full-length and truncated protein products, with only the former serving as membrane-bound receptors to activate natural killer (NK) cells. We have previously shown that full-length KIR2DS4 was associated with relatively high viral load and accelerated heterosexual HIV-1 transmission. Our objective here was to provide confirmatory data and to offer new insights about the potential mechanisms. Methodology/Principal Findings Mixed models for repeated (longitudinal) outcome measurements on 207 HIV-1 seropositive American youth revealed an association of full-length KIR2DS4 with relatively high viral load and low CD4+ T-cell count (p<0.01 for both). Depending on KIR2DS4 expression (presence or absence) on cell surface, NK cells from 43 individuals with untreated, chronic HIV-1 infection often differed in functional properties, including degranulation and secretion of IFN-γ and MIP-1β. In particular, polyfunctional NK cells were enriched in the KIR2DS4-positive subset. Conclusions/Significance Full-length KIR2DS4 promotes HIV-1 pathogenesis during chronic infection, probably through the maintenance of an excessively pro-inflammatory state.
    Full-text · Article · Jun 2014 · PLoS ONE
  • Richard A. Kaslow · Emily J. Erbelding · Paul A. Goepfert
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    ABSTRACT: Human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) are retroviruses that attack and destroy cells essential to the regulation of immune function, primarily the CD4-bearing lymphocytes. Of the two viruses, HIV-1 accounts for the vast majority of infection, morbidity and mortality in the world. Some newly infected individuals experience a mononucleosis-like syndrome, and all undergo a deterioration of cell-mediated immunity. Although the rate of loss is highly variable, in the absence of treatment the loss is eventually profound enough to produce a fatal acquired immunodeficiency syndrome (AIDS) consisting of a spectrum of opportunistic infections and neoplasms. Since the emergence of AIDS in 1981, HIV-1 has spread by sexual, parenteral, and perinatal routes to reach pandemic proportions. Some 35 million people worldwide are currently infected with HIV-1, but the affected populations vary greatly by geographic, socioeconomic and behavioral factors. Men who have sex with men were initially and still are at high risk, but the infection has had huge numerical impact on heterosexuals in sub-Saharan Africa and Asia and on injection drug users in Eastern Europe, Southeast Asia and urban areas elsewhere. Numerous alternative therapeutic antiretroviral agents combined in increasingly simpler and less toxic regimens have proved capable of suppressing viremia to undetectable levels and often essentially halting the disease process. However, HIV-1 mutates easily and establishes seemingly permanent reservoirs from which the virus has proved difficult to dislodge entirely with even the most aggressive therapy. Nevertheless, international organizations have accepted the challenge of mobilizing to deliver those agents in concerted intervention programs tailored to local epidemiologic and socioeconomic conditions. Primary prevention HIV-1 infection at the population level has depended heavily on implementation of programs for screening of blood supplies, behavioral risk reduction, male circumcision, and administration of vaginal microbicides or systemic suppression of ulcerative genital co-infections. Success has been mixed and slow in coming. Vaccine development has been frustratingly slower. Discovery of a correlate of broadly protective immunity has eluded the most intense vaccinologic research, and trials of early prototype vaccines have been largely disappointing. A more promising preventive strategy has been a byproduct of widespread therapeutic intervention: treat infected individuals to prevent transmission to their uninfected partners, i.e., treatment as prevention. Whether expansive application of this strategy will prove to be the turning point in the battle against HIV/AIDS remains to be seen. © 2014 Springer Science+Business Media New York. All rights are reserved.
    No preview · Chapter · Jun 2014
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    ABSTRACT: Multiple major histocompatibility complex (MHC) loci encoding human leukocyte antigens (HLA) have allelic variants unequivocally associated with differential immune control of HIV-1 infection. Fine mapping based on single nucleotide polymorphisms (SNPs) in the extended MHC (xMHC) region is expected to reveal causal or novel factors and to justify a search for functional mechanisms. We have tested the utility of a custom fine-mapping platform (the ImmunoChip) for 172 HIV-1 seroconverters (SCs) and 449 seroprevalent individuals (SPs) from Lusaka, Zambia, with a focus on more than 6400 informative xMHC SNPs. When conditioned on HLA and nongenetic factors previously associated with HIV-1 viral load (VL) in the study cohort, penalized approaches (HyperLasso models) identified an intergenic SNP (rs3094626 between RPP21 and HLA-E) and an intronic SNP (rs3134931 in NOTCH4) as novel correlates of early set-point VL in SCs. The minor allele of rs2857114 (downstream from HLA-DOB) was an unfavorable factor in SPs. Joint models based on demographic features, HLA alleles and the newly identified SNP variants could explain 29% and 15% of VL variance in SCs and SPs, respectively. These findings and bioinformatics strongly suggest that both classic and nonclassic MHC genes deserve further investigation, especially in Africans with relatively short haplotype blocks.Genes and Immunity advance online publication, 1 May 2014; doi:10.1038/gene.2014.16.
    Full-text · Article · May 2014 · Genes and immunity
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    ABSTRACT: In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B⁎53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2–3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies.
    Full-text · Article · Jan 2014 · Virology
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    ABSTRACT: Like other members of the γ-herpesvirus family, human herpes virus 8 (HHV-8), the etiologic agent of classic and HIV-related Kaposi's sarcoma (HIV-KS) acquired and evolved several human genes with key immune modulatory and cellular growth control functions. The encoded viral homologs substitute for their human counterparts but escape cellular regulation, leading to uncontrolled cell proliferation. We postulated that DNA variants in the human homologs of viral genes that potentially alter the expression or the binding of the encoded factors controlling the antiviral response may facilitate viral interference. To test whether cellular homologs are candidate susceptibility genes, we evaluated the association of DNA variants in 92 immune-related genes including 7 cellular homologs with the risk for HIV-KS in a matched case and control study nested in the Multicenter AIDS Cohort Study. Low- and high-risk gene-by-gene interactions were estimated by multifactor dimensionality reduction and used as predictors in conditional logistic models. Among the most significant gene interactions at risk (OR=2.84-3.92; Bonferroni- adjusted p= 9.9 x10(-3) - 2.6 x 10(-4) ), three comprised human homologs of two latently expressed viral genes, cyclin D1 (CCND1) and interleukin-6 (IL-6), in conjunction with angiogenic genes (VEGF, EDN-1 and EDNRB). At lower significance thresholds (adjusted p < 0.05), human homologs related to apoptosis (CFLAR) and chemotaxis (CCL2) emerged as candidates. This "proof of concept" study identified human homologs involved in the regulation of type I interferon-induced signaling, cell cycle and apoptosis potentially as important determinants of HIV-KS © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Jan 2014 · International Journal of Cancer
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    ABSTRACT: B cells are pivotal regulators of acquired immune responses, and recent work in both experimental murine models and humans has demonstrated that subtle changes in the regulation of B cell function can substantially alter immunological responses. The balance of negative and positive signals in maintaining an appropriate B cell activation threshold is critical in B lymphocyte immune tolerance and autoreactivity. FcγRIIb (CD32B), the only recognized Fcγ receptor on B cells, provides immunoglobulin G (IgG)-mediated negative modulation through a tyrosine-based inhibition motif, which down-regulates B cell receptor-initiated signaling. These properties make FcγRIIb a promising target for antibody-based therapy. We report the discovery of allele-dependent expression of the activating FcγRIIc on B cells. Identical to FcγRIIb in the extracellular domain, FcγRIIc has a tyrosine-based activation motif in its cytoplasmic domain. In both human B cells and B cells from mice transgenic for human FcγRIIc, FcγRIIc expression counterbalances the negative feedback of FcγRIIb and enhances humoral responses to immunization in mice and to BioThrax vaccination in a human anthrax vaccine trial. Moreover, the FCGR2C-ORF allele is associated with the risk of development of autoimmunity in humans. FcγRIIc expression on B cells challenges the prevailing paradigm of unidirectional negative feedback by IgG immune complexes via the inhibitory FcγRIIb, is a previously unrecognized determinant in human antibody/autoantibody responses, and opens the opportunity for more precise personalized use of B cell-targeted antibody-based therapy.
    No preview · Article · Dec 2013 · Science translational medicine

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  • No preview · Conference Paper · Nov 2013
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    Full-text · Conference Paper · Oct 2013
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    ABSTRACT: As a mechanism of self-protection, signal peptides cleaved from human leukocyte antigen (HLA) class I products bind to HLA-E before the complex interacts with the natural killer (NK) cell receptor CD94/NKG2A to inhibit NK-mediated cell lysis. Two types of the signal peptides differ in their position 2 (P2) anchor residue, with P2-methionine (P2-M) having higher HLA-E binding affinity than P2-threonine (P2-T). All HLA-A and HLA-C molecules carry P2-M, whereas HLA-B products have either P2-M or P2-T. Epidemiologic evidence suggests that P2-M is unfavorable in the context of HIV-1 infection, being associated with accelerated acquisition of HIV-1 infection in two African cohorts. To begin elucidating the functional mechanism, we studied NK-mediated killing of CD4(+) T-cells and monocyte-derived macrophages infected with two laboratory-adapted HIV-1 strains and two transmitted/founder (T/F) viruses. In the presence of target cells derived from individuals with the three HLA-B P2 genotypes (M/M, M/T, and T/T), NK-mediated cytolysis was consistently elevated for P2-T in a dose-dependent manner for all cell and virus combinations tested (p=0.008-0.03). Treatment of target cells with an anti- HLA-E monoclonal antibody restored NK-mediated cytolysis of cells expressing P2-M. Observations on cell lysis were also substantiated by measurements of HIV-1 p24 antigen in the culture supernatants. Overall, our experiments indicate that the anti-HIV-1 function mediated by NK cells is compromised by P2-M, corroborating the association of HLA-B genotype encoding P2-M with accelerated HIV-1 acquisition.
    No preview · Article · Aug 2013 · Clinical & Experimental Immunology
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    ABSTRACT: Anthrax and its etiologic agent remain a biological threat. Anthrax vaccine is highly effective, but vaccine-induced IgG antibody responses vary widely following required doses of vaccinations. Such variation can be related to genetic factors, especially genomic copy number variants (CNVs) that are known to be enriched among genes with immunologic function. We have tested this hypothesis in two study populations from a clinical trial of anthrax vaccination. We performed CNV-based genome-wide association analyses separately on 794 European Americans and 200 African-Americans. Antibodies to protective antigen were measured at week 8 (early response) and week 30 (peak response) using an enzyme-linked immunosorbent assay. We used DNA microarray data (Affymetrix 6.0) and two CNV detection algorithms, hidden markov model (PennCNV) and circular binary segmentation (GeneSpring) to determine CNVs in all individuals. Multivariable regression analyses were used to identify CNV-specific associations after adjusting for relevant non-genetic covariates. Within the 22 autosomal chromosomes, 2,943 non-overlapping CNV regions were detected by both algorithms. Genomic insertions containing HLA-DRB5, DRB1 and DQA1/DRA genes in the major histocompatibility complex (MHC) region (chromosome 6p21.3) were moderately associated with elevated early antibody response (β = 0.14, p = 1.78×10(-3)) among European Americans, and the strongest association was observed between peak antibody response and a segmental insertion on chromosome 1, containing NBPF4, NBPF5, STXMP3, CLCC1, and GPSM2 genes (β = 1.66, p = 6.06×10(-5)). For African-Americans, segmental deletions spanning PRR20, PCDH17 and PCH68 genes on chromosome 13 were associated with elevated early antibody production (β = 0.18, p = 4.47×10(-5)). Population-specific findings aside, one genomic insertion on chromosome 17 (containing NSF, ARL17 and LRRC37A genes) was associated with elevated peak antibody response in both populations. Multiple CNV regions, including the one consisting of MHC genes that is consistent with earlier research, can be important to humoral immune responses to anthrax vaccine adsorbed.
    Full-text · Article · May 2013 · PLoS ONE
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    ABSTRACT: Interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a “heterozygote advantage.” Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95, P = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively. Finally, homozygosity at an increasing number (≥4) of HLA loci was significantly correlated with a reduction in LP response (P < 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors (Bacillus anthracis LF and EF) than HLA-homozygous subjects.
    Full-text · Article · May 2013 · Infection and immunity
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    Aimee M Merino · Kui Zhang · Richard A Kaslow · Brahim Aissani
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    ABSTRACT: DNA variants in the tumor necrosis factor-α (TNF) and linked lymphotoxin-α genes, and specific alleles of the highly polymorphic human leukocyte antigen B (HLA-B) gene have been implicated in a plethora of immune and infectious diseases. However, the tight linkage disequilibrium characterizing the central region of the human major histocompatibility complex (MHC) containing these gene loci has made difficult the unequivocal interpretation of genetic association data. To alleviate these difficulties and facilitate the design of more focused follow-up studies, we investigated the structure and distribution of HLA-B-specific MHC haplotypes reconstructed in a European population from unphased genotypes at a set of 25 single nucleotide polymorphism sites spanning a 66-kilobase long region across TNF. Consistent with the published data, we found limited genetic diversity across the so-called TNF block, with the emergence of seven common MHC haplotypes, termed TNF block super-haplotypes. We also found that the ancestral haplotype 8.1 shares a TNF block haplotype with HLA-B*4402. HLA-B*5701, a known protective allele in HIV-1 pathogenesis, occurred in a unique TNF block haplotype.
    Full-text · Article · Apr 2013 · Immunogenetics

Publication Stats

18k Citations
2,118.70 Total Impact Points

Institutions

  • 1996-2015
    • University of Alabama at Birmingham
      • • Department of Epidemiology
      • • Department of Medicine
      Birmingham, Alabama, United States
    • Gezond Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1998-2014
    • University of Alabama
      Tuscaloosa, Alabama, United States
    • Uniformed Services University of the Health Sciences
      • Department of Preventive Medicine & Biometrics
      베서스다, Maryland, United States
  • 1990-2002
    • Johns Hopkins University
      • Department of Epidemiology
      Baltimore, Maryland, United States
  • 2001
    • Duke University
      Durham, North Carolina, United States
  • 1994-2001
    • Ben-Gurion University of the Negev
      • Faculty of Health Sciences
      Be'er Sheva`, Southern District, Israel
  • 1987-2001
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      Maryland, United States
  • 1996-1999
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      Maryland, United States
  • 1988-1998
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, Maryland, United States
    • Hackensack University Medical Center
      Хакенсак, New Jersey, United States
  • 1997
    • Cornell University
      Итак, New York, United States
  • 1991-1996
    • National Institutes of Health
      • • National Institute of Allergy and Infectious Diseases (NIAID)
      • • Branch of Epidemiology (EPI)
      • • Division of Microbiology and Infectious Diseases (DMID)
      Maryland, United States
    • County of Los Angeles Public Health
      Los Angeles, California, United States