Interleukin-1A May Illuminate Differential Effects of the Retinal Artery Caliber in HIV Patients

Background: Retinal artery caliber (RAC) is narrower in human immunodeficiency virus (HIV)-infected patients beginning antiretroviral therapy (ART). We aimed to assess associations between variations in genes encoding inflammatory mediators and natural killer receptors and retinal artery caliber (RAC) in HIV patients beginning ART.Materials and Methods: Seventy-nine HIV positive patients beginning ART with less than 200 cluster of differentiation (CD) 4 T-cells/μL were recruited. Examinations were performed before ART (V0) and at months 3, 6 and 12 (V3, V6, V12). The study was approved by ethics committees and informed consent was obtained from each subject.Results: Right and left RAC of the HIV patients were narrower than healthy controls (p=0.016 for right RAC) and narrowed further on ART, but demographic associations with the right and left RAC were not identical. Here we show that polymorphisms in genes encoding NK receptors or TNF activity had no significant impact, but right RAC was associated with carriage of allele 2 at IL1A+4845 (p=0.037 after 12 months on ART).Conclusion: Overall the paradoxical reduction in the RAC in HIV patients responding to ART was not modified by genotypes known to affect NK cell function or TNF responses, but IL1A genotype may modify the decline in the right RAC.Keywords: anti-retroviral therapy, CMV, HIV, IL1A, retinal artery caliber

The Innate Biologies of Adaptive Antigen Receptors

Nonclonal innate immune responses mediated by germ line–encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line–encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/β chains.

Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of human leucocyte antigen (HLA)-B27 alleles. HLA-E molecules are non-classical major histocompatibility complex (MHC) class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis.‘’ObjectiveTo analyse the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27-positive patients with AS and healthy controls (HC) bearing the AS-associated B*2705 and the non-AS-associated B*2709 alleles.MethodsThe level of surface expression of HLA-E molecules on CD14+ peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27-negative HC using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3−CD56+ NK cells.ResultsHLA-E expression in CD14+ cells was significantly higher in patients with AS (587.0, IQR 424–830) compared with B*2705 HC (389, IQR 251.3–440.5; p=0.0007), B*2709 HC (294.5, IQR 209.5–422; p=0.0004) and HLA-B27-negative HC (380, IQR 197.3–515.0; p=0.01). A higher number of NK cells expressing NKG2A compared with NKG2C were found in all cohorts analysed, as well as a higher cell surface density.ConclusionThe higher surface level of HLA-E molecules in patients with AS compared with HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis, accounting for the previously reported association between HLA-E and AS.