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


ABSTRACT: Ankylosing 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.''.To 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.The 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.HLA-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.The 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.

SUBMITTER: Cauli A 

PROVIDER: S-EPMC6045714 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Cauli Alberto A   Dessole Grazia G   Piga Matteo M   Angioni Maria Maddalena MM   Pinna Silvia S   Floris Alberto A   Congia Mattia M   Mascia Enrico E   Paladini Fabiana F   Tedeschi Valentina V   Sorrentino Rosa R   Fiorillo Maria Teresa MT   Mathieu Alessandro A  

RMD open 20180713 2


<h4>Background</h4>Ankylosing 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.''.<h4>Objective</h4>To analyse the expression of HLA-E and the CD  ...[more]

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