LILRA3 deletion is a genetic risk factor of HIV infection

Objective: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.Design:Case and control study.Methods: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.Results: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.Conclusion:The homozygous LILRA3 deletion is associated with a higher susceptibility for HIV disease and with a faster disease progression.