title: Genome-wide scan in two groups of HIV-infected patients treated with dendritic cell-based immunotherapy.
abstract: We performed a retrospective genome-wide association study in HIV-infected individuals who were treated with dendritic cell-based immunotherapy in clinical trials performed by two research groups (Spain and Brazil). We aimed to identify host genetic variants influencing treatment response. The Illumina Human Core Exome 12 v 1.0 Bead Chip with over 250,000 markers was used to analyze genetic factors affecting treatment response. Additionally, we performed a meta-analysis of the results obtained from Spanish and Brazilian patients. We identified a genetic variation (rs7935564 G allele) in TRIM22 gene, which encodes TRIM22 protein acting like a HIV restriction factor, as being associated with good response to dendritic cell-based immunotherapy. We then verified the impact of TRIM22 rs7935564 SNP in susceptibility to HIV infection and disease progression by assessing the influence of biogeographic ancestry in the distribution of allelic and genotype frequencies in three populations from Italy, Brazil and Zambia. TRIM22 rs7935564 genotyping indicated association of G rs7935564 allele with long-term non-progression of HIV disease in Italian patients, thus corroborating our hypothesis that it is involved as a restriction factor in dendritic cell-based immunotherapy response. TRIM22 rs7935564 polymorphism was associated with good response to dendritic cell-based immunotherapy. We hypothesize that in selecting patients for treatment, there is a possible bias related to the natural presence of restriction factors that are genetically determined and could influence final outcome of therapy.
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, Brazil.|Laboratory of Immunopathology Keizo Azami (LIKA), Federal University of Pernambuco, Recife, Brazil.
authors.forename: Ronald
authors.initials: R
authors.lastname: Moura Rodrigues
authors.affiliation: Retrovirology and Cellular Immunopathology Laboratory, AIDS Research Group, Catalan Project for the Development of an HIV Vaccine (HIVACAT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Monserrat
authors.initials: M
authors.lastname: Plana
authors.affiliation: Infectious Diseases Unit, AIDS Research Group, Catalan Project for the Development of an HIV Vaccine (HIVACAT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/1, Zip code: 34137, Trieste, Italy.|Department of Medicine, Surgery and Health Sciences,, University of Trieste, Trieste, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Zupin
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/1, Zip code: 34137, Trieste, Italy. crovelser@gmail.com.|Department of Medicine, Surgery and Health Sciences,, University of Trieste, Trieste, Italy. crovelser@gmail.com.
authors.forename: Sergio
authors.identifier: 0000-0001-8493-1168
authors.initials: S
authors.lastname: Crovella
mesh_terms: D000328:Adult; D001938:Brazil; D002648:Child; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007558:Italy; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D012189:Retrospective Studies; D013030:Spain; D016896:Treatment Outcome; D000070584:Tripartite Motif Proteins / Q000235:genetics*
chemical_list: D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins
keywords: Dendritic cells; Genome-wide; HIV; Immune-therapy; SNPs; TRIM22