Background Behçet’s disease is a multifactorial inflammatory disease of unknown etiology, and it is strongly associated with HLA-B51. The pathogenic mechanisms related to HLA-B51 have yet to be identified, and one of them may be linked to its properties of slow folding and promiscuous peptide binding.
Objectives This study aimed to analyze the unfolded protein response (UPR) in Behçet’s disease with respect to HLA-B51 status by investigating XBP1 splicing as well as the expression of XBP1, BiP and HLA-B genes.
Methods This pilot study group consisted of 84 patients with Behçet’s disease and 30 healthy controls. Peripheral blood samples were collected after obtaining written informed consent, and monocytes were isolated for gene expression analyses.XBP1 splicing was investigated in cDNA samples by amplifying the region of XBP1 gene containing the splice site, and unspliced and spliced forms of XBP1 were determinedby separating PCR products on 4% agarose gels. Expression of XBP1, BiP and HLA-B genes in monocytes were analyzed by real-time quantitative PCR analysis using LightCycler (Roche) relative to the expression of β2 microglobulinas the housekeeping gene. Results were evaluated according to the disease activity and HLA-B51 status of patients with Behçet’s disease.
Results Spliced form of XBP1 was detected in 19 (%22.6) Behçet’s patients and in none of the healthy controls. Relative XBP1 expression level was found to be reduced in patients with Behçet’s disease compared to healthy controls (0,0036 vs 0,0058; P=0.0012). In patients with manifestations indicating an active disease at the time of blood collection (n=20), XBP1 expression was higher than the expression in inactive patients. On the other hand, expression of another UPR related gene, BiP was significantly increased in the patients compared to healthy controls (0,0432 vs 0,0299, P=0.02). HLA-B expression was also increased in Behçet’s patients compared to healthy controls (2,2968 vs 1,7901; P=0.09), and it was slightly higher in HLA-B51 positive patients compared to the remaining patients carrying other HLA-B alleles. However, those differences between the HLA-B expressions were not statistically significant. There was no relationship between the XBP1 splicing and expression level and HLA-B51 positivity.
Conclusions The results of this pilot study suggest that XBP1 may have a role in the pathogenesis of Behçet’s disease, and relatively reduced expression of XBP1 may be associated with an increased risk for UPR-related inflammatory reaction in the patients. No association was observed between the HLA-B51 status and XBP1 expression or XBP1 splicing, and our results do not support an HLA-B51-related UPR in the pathogenesis. Reduced XBP1 expression has been associated with inflammatory bowel disease in animal models, and this pilot study warrants further studies to explore the involvement of XBP1 through both UPR and non-classical XBP1 activation pathways in the development of Behçet’s disease.
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.