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HLA-B27 is the strongest genetic risk factor for ankylosing spondylitis (AS), but how it contributes to AS remains unknown. Increased endoplasmic reticulum stress, triggered by misfolding of HLA-B27 heavy chains, and activation of the unfolded protein response (UPR) have been proposed as underlying mechanisms.1 Studies in the HLA-B27/β2 microglobulin transgenic rat show a temporal and quantitative relationship between HLA-B27 upregulation and activation of the UPR in macrophages of diseased rats.2 ,3 In AS patients, some small studies show conflicting results.4–7 We aimed to determine if the HLA-B27-related UPR, present in transgenic rats, is relevant in blood and synovial tissues of AS patients. We compared ex vivo UPR gene expression in synovium and blood from AS patients with expression in the same tissues and cells of healthy controls and patients with other rheumatic diseases.
We obtained synovial tissues from inflamed knees from patients with AS, other forms of spondyloarthritis (SpA), rheumatoid arthritis …