Human LILRB1 ELISA Matched Antibody Pair

Elite controllers maintain undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, but the correlates of immune protection in this patient population are ill defined. Here, we demonstrate that in comparison to patients with progressive HIV-1 infection or healthy persons not infected with HIV-1, elite controllers have circulating myeloid dendritic cells with significantly increased antigen-presenting properties, while their ability to secrete proinflammatory cytokines is substantially diminished. This unique functional profile is associated with a distinct surface expression pattern of immunomodulatory leukocyte-immunoglobulin- like receptors (LILR) and a strong and selective upregulation of LILRB1 and LILRB3. Blockade of these two receptors by monoclonal antibodies or short interfering RNA (siRNA) abrogated the specific antigen-presenting properties of dendritic cells, implying an important regulatory role of these molecules. These data reveal previously unrecognized innate components of immune protection against HIV-1 in elite controllers and offer novel perspectives for the manipulation of host immunity for the prevention and treatment of HIV-1 infection.

Most human immunodeficiency virus (HIV) patients are seropositive for cytomegalovirus (CMV) but a smaller proportion experience end-organ disease. This observation may reflect variations in genes affecting inflammatory and natural killer cell responses. DNA samples were collected from 240 HIV-infected patients followed at the University Hospitals/Case Medical Center (Cleveland, OH) between 1993 and 2008. Seventy-eight patients (African Americans = 41, Caucasians = 37) experienced CMV disease. Genotypes were determined using allele-specific fluorescent probes or multiplex polymerase chain reaction sequence-specific primers. IL12B3'UTR*(1) and SLC11A1 D543N*(1,2) were associated with CMV disease in African American patients (p = 0.04 and p = 0.02, respectively). IL10-1082*(1,2) and LILRB1 I142T*(1) were associated with CMV disease in Caucasians (p = 0.02 and p = 0.07, respectively). DARC T-46C*(1) and CD14 C-159T*(2) were associated with low nadir CD4(+) T cell counts in African American patients (p = 0.002 and p = 0.01, respectively). Caucasian patients carrying TNFA-308*2, TNFA-1031*(2), IL2-330*(1), CCL2-2518*(2), or LILRB1 I142T*(1) had significantly lower nadir CD4(+) T cells in a bootstrapped multivariable model (p = 0.006-0.02). In general, polymorphisms associated with CMV disease and CD4(+) T cell counts were distinct in Caucasian and African American patients in the United States. The LILRB1 I142T polymorphism was associated with both CMV disease and low nadir CD4(+) T cell counts in Caucasians, but the clearest determinant of low nadir CD4(+) T cell count in African American patients was DARC T-46C. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.