Anti-apolipoprotein A-1 autoantibodies are associated with immunodeficiency and systemic inflammation in HIV patients

OBJECTIVES: To determine the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in HIV patients and explore their association with biological features of HIV infection and different inflammatory biomarkers. We also evaluated their impact on CD4+ lymphocytes survival. METHODS: Anti-apoA-1 IgG plasma levels were assessed by ELISA in 237 HIV positive patients from a national prospective cohort with no current lipid-lowering therapy. RESULTS: 58% of patients were found positive for anti-apoA-1 IgG and were associated with lower CD4+ counts, but higher viremia and systemic inflammation. Logistic regression analyses indicated that high anti-apoA-1 IgG levels were associated with a 16-fold increased risk of displaying low CD4+ levels, independently of HIV-RNA levels and treatment (adjusted Odds ratio [OR]:16.1, 95% Confidence Interval[95%CI]:1.80-143.6;P=0.01), and a 6-fold increased risk of having a detectable viremia, independently of antiretroviral treatment (OR:5.47;95%CI:1.63-18.36; P=0.006). In vitro, anti-apoA-1 IgG induced a dose and time-dependent CD4+ apoptosis that was increased by exposure to HIV-RNA. CONCLUSIONS: In HIV patients, anti-apoA-1 IgG levels are associated with low CD4+ counts, high viremia and a pro-inflammatory systemic profile. Experimental evidences showed that anti-apoA-1 IgG can promote CD4+ lymphocyte apoptosis trough undefined pathways. The clinical implications of these findings require further investigations.