title: LILRA3 deletion is a genetic risk factor of HIV infection.
abstract: The aim of this study is to analyse the influence of LILRA3 and the genetic leukocyte immunoglobulin-like receptor 3 (LILRA3) deletion on transmission and clinical course of HIV infection.
  
  
  
  Case and control study.
  
  
  
  LILRA3 genotypes were determined by PCR. HIV patients were categorized into short-term progressors, normal progressors and long-term nonprogressors according to the clinical course. Functional studies were performed using real-time PCR, intracellular flow cytometry and ELISA.
  
  
  
  The prevalence of the homozygous LILRA3 deletion was higher in HIV-positive individuals (n = 439) than in controls (n = 651) (P = 0.02). The disease progression was faster in homozygously deleted patients with more short-term progressors than in heterozygous (P = 0.03) and homozygously positive (P = 0.002) individuals. These results have been confirmed in a seroconverter cohort (n = 288). The frequency of the homozygous deletion in the confirmation cohort was higher than in controls (P = 0.04). Combining both cohorts, the proportion of homozygously LILRA3-deleted individuals was 6.2% in HIV-infected patients (n = 727) vs. 3.2% in controls (P = 0.01). Functional analysis revealed an upregulation of the LILRA3 gene in real-time PCR in treated patients when compared with untreated patients (P = 0.007) and controls (P = 0.02) resulting in a higher LILRA3 expression in CD4 (P = 0.008) and CD14 (P = 0.02) cells of untreated patients in intracellular flow cytometry. LILRA 3 concentrations in the sera were similar between the groups, in untreated patients a correlation between viral load and LILRA3 concentration was found.
  
  
  
  The homozygous LILRA3 deletion is associated with a higher susceptibility for HIV disease and with a faster disease progression.
authors.affiliation: aClinic for Immunology and Rheumatology, Hannover Medical School (MHH), Hannover bDepartment of Infectious Diseases cDepartment of Infectious Diseases Epidemiology, Robert Koch-Institute, Berlin dAESKU Diagnostics, Wendelsheim eGerman Center for Infection Research (DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Ahrenstorf
authors.forename: Hui Zhi
authors.initials: HZ
authors.lastname: Low
authors.forename: Katja
authors.initials: K
authors.lastname: Kniesch
authors.forename: David
authors.initials: D
authors.lastname: Ordonez
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer-Olson
authors.forename: Fareed
authors.initials: F
authors.lastname: Ahmad
authors.forename: Claudia
authors.initials: C
authors.lastname: Kücherer
authors.forename: Barbara
authors.initials: B
authors.lastname: Gunsenheimer-Bartmeyer
authors.forename: Matthias
authors.initials: M
authors.lastname: Stoll
authors.forename: Torsten
authors.initials: T
authors.lastname: Matthias
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology / Q000635:transmission; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: C530062:LILRA3 protein, human; D011971:Receptors, Immunologic