Background Ankylosing Spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of HLA-B27 alleles, with the exception of B*2706 and B*2709. GWAS studies have revealed that other genes are also involved in AS pathogenesis such as ERAP1 which is able to cleave TNFR1 and IL-1R2 cell surface receptors, supposed to play a pivotal role in AS pathogenesis.
Objectives To analyze the cell surface expression of TNFR1 and IL-1R2 receptors and the possible influence of ERAP1 allelic variance.
Methods The percentage of CD14 negative peripheral blood mononuclear cells (PBMC) expressing TNFR1 and IL-1R2 receptors on the cell surface was evaluated in 12 HLA-B*2705 patients with AS, 12 HLA-B*2705 healthy subjects (HC) and 12 HLA-B*2709 HC by means of flow cytometry analysis and CD120a and CD121b monoclonal antibodies, respectively. Patients and controls were genotyped for two ERAP1 SNPs associated with AS (rs27044 C/G and rs30187 C/T). Values were expressed as median percentage of positive cells (interquartile range). The differences between AS patients and HC were analyzed by Mann Whitney U-test.
Results TNFR1 expression on PBMC was significantly higher in AS patients (35.5 IQR 15.9-60.4) compared to B*2705 HC (18.9 IQR 9.7-25.5, p=0.04) and B*2709 HC (13.1 IQR 9.3-21.5, p=0.02). IL-1R2 was also significantly higher in AS patients (1.5 IQR 0.6-2.5) compared to B*2705 HC (0.2 IQR 0.1-0.8, p=0.01) and B*2709 HC (0.6 IQR 0.1-1.6, p=ns). The majority of AS patients and HC were heterozygous both for rs27044 (C/G) and rs30187 (C/T); the higher numbers of TNFR1 and IL-1R2 positive cells found in AS patients compared to HC were not due to differences in the ERAP1 allelic distribution in patients and controls as shown in the figure below:
Conclusions This study shows a higher expression of TNFR1 and IL-1R2 on the PBMC surface of AS patients compared to B*2705 and B*2709 regardless of ERAP1 allelic variance, underlining the important role of these two cytokines in the pathogenesis of AS.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.