Dataset Information

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes.

ABSTRACT: We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus-infected patients. We studied the relationship between KIR-human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4-003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4-003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.

SUBMITTER: Wawina-Bokalanga T

PROVIDER: S-EPMC7774578 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes.

Wawina-Bokalanga Tony T Vanmechelen Bert B Lhermitte Valentine V Martí-Carreras Joan J Vergote Valentijn V Koundouno Fara Raymond FR Akoi-Boré Joseph J Thom Ruth R Tipton Tom T Steeds Kimberley K Moussa Kéita Balla KB Amento Ablam A Laenen Lies L Duraffour Sophie S Gabriel Martin M Ruibal Paula P Hall Yper Y Kader-Kondé Mandy M Günther Stephan S Baele Guy G Muñoz-Fontela Cesar C Van Weyenbergh Johan J Carroll Miles W MW Maes Piet P

Emerging infectious diseases 20210101 1

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus-infected patients. We studied the relationship between KIR-human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4-003 and inhibitory 2DL5 genes were significantly more common among persons who die ...[more]

PMID: 33350932

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Project description:Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10-4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary.

Project description:BackgroundAssociations between human leukocyte antigens (HLA) alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC), the major histologic subtype. We evaluated the association between HLA class I (A, B, and C) and class II (DRB1 and DQB1) loci and risk of cervical adenocarcinoma (ADC), a less common but aggressive histologic subtype.MethodsWe pooled data from the Eastern and Western US Cervical Cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n = 630 ADC; n = 775 controls). Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type) and 38 non a priori common alleles, as odds ratios (OR) and 95% confidence intervals (CI), adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls.ResultsThree of the a priori alleles were significantly associated with decreased risk of ADC [DRB1*13:01 (OR = 0.61; 95% CI: 0.41-0.93), DRB1*13:02 (OR = 0.49; 95% CI: 0.31-0.77), and DQB1*06:03 (OR = 0.64; 95% CI: 0.42-0.95)]; one was associated with increased risk [B*07:02 (OR = 1.39; 95% CI: 1.07-1.79)]. Among alleles not previously reported, DQB1*06:04 (OR = 0.46; 95% CI: 0.27-0.78) was associated with decreased risk of ADC and remained significant after correction for multiple comparisons, and C*07:02 (OR = 1.41; 95% CI: 1.09-1.81) was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR = 1.33; 95% CI: 1.01-1.76) and decreased risk with DRB1*13:02/DQB1*06:04 (OR = 0.41; 95% CI: 0.21-0.80).ConclusionRESULTS suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18-related tumors, consistent with the hypothesis that HLA recognition is HPV type-specific.

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Dataset Information

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes.

Publications

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes.

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