The HLA-C*04:01/KIR2DS4 gene combination and human leukocyte antigen alleles with high population frequency drive rate of HIV disease progression
| Autor: | William H. Hildebrand, Jorge Sanchez, Carmela Ganoza, Lupe Gomez, Aldo Lucchetti, Christian Brander, Steven Cate, Susana Pérez-Álvarez, Javier Ibarrondo, Alex Olvera, Nicole F. Bernard, Javier R Lama |
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| Přispěvatelé: | Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades, Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. GRBIO - Grup de Recerca en Bioestadística i Bioinformàtica |
| Rok vydání: | 2015 |
| Předmět: |
Linkage disequilibrium
killer-cell immunoglobulin-like receptor Ciències de la salut::Medicina [Àrees temàtiques de la UPC] Immunology Killer-cell immunoglobulin-like receptor Population type-1 infection HIV Infections HLA-C Antigens Human leukocyte antigen adaptation Biology human leukocyte antigen class I HLA-C Gene Frequency Receptors KIR Antígens HLA level Peru VIH (Virus) Humans Immunology and Allergy Genetic Predisposition to Disease education Allele frequency risk education.field_of_study kir2ds4 hla class-i Viral Load CD4(+) cell counts t-cell responses Sida -- Tractament HIV infection Virology CD4 Lymphocyte Count viral load 90 Operations research mathematical programming [Classificació AMS] Cross-Sectional Studies Infectious Diseases Disease Progression immune Viral load associations KIR2DS4 aids |
| Zdroj: | RIUVic. Repositorio Institucional de la Universidad de Vic instname UPCommons. Portal del coneixement obert de la UPC Universitat Politècnica de Catalunya (UPC) Recercat. Dipósit de la Recerca de Catalunya Universitat Jaume I |
| Popis: | Objective: The objective of this study is to identify human leukocyte antigen (HLA) class I and killer-cell immunoglobulin-like receptor (KIR) genotypes associated with different risks for HIV acquisition and HIV disease progression. Design: A cross-sectional study of a cohort of 468 high-risk individuals (246 HIVpositive and 222 HIV-negative) from outpatient clinics in Lima (Peru´ ). Methods: The cohort was high-resolution HLA and KIR-typed and analysed for potential differences in single-allele frequencies and allele combinations between HIVpositive and HIV-negative individuals and for associations with HIV viral load and CD4þ cell counts in infected individuals. Results: HLA class I alleles associated with a lack of viral control had a significantly higher population frequency than relatively protective alleles (P¼0.0093), in line with a rare allele advantage. HLA-A 02 : 01 and HLA-C 04 : 01 were both associated with high viral loads (P¼0.0313 and 0.0001, respectively) and low CD4þ cell counts (P¼0.0008 and 0.0087, respectively). Importantly, the association between HLAC 04 : 01 and poor viral control was not due to its linkage disequilibrium with other HLA alleles. Rather, the coexpression of its putative KIR ligand KIR2DS4f was critically linked to elevated viral loads. Conclusion: These results highlight the impact of population allele frequency on viral control and identify a novel association between HLA-C 04 : 01 in combination with KIR2DS4f and uncontrolled HIV infection. Our data further support the importance of the interplay of markers of the adaptive and innate immune system in viral control. |
| Databáze: | OpenAIRE |
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