OBJECTIVE To investigate whether unfolded protein response (UPR) plays a role in the pathogenesis of spondyloarthritis (SpA), and to assess UPR-related gene expression in SpA and other arthritis patients.
Eighteen patients with SpA, 12 with rheumatoid arthritis (RA) and 6 with osteoarthritis (OA) were recruited. Macrophages were isolated from synovial fluid samples by immunomagnetic separation. The expression of UPR-regulated genes, including binding immunoglobulin protein (BiP), glucose-regulated protein 94 (GRP94), C/EBP homologous protein (CHOP), growth arrested and DNA damage-inducible 34 (GADD34), X-box binding protein 1 (XBP-1) and endoplasmic reticulum DnaJ homolog 4 (ERdj4), was tested by real time polymerase chain reaction (PCR) .
Compared with macrophages in OA patients, the expression of BiP and GRP94 mRNA[ (6.06 ± 2.08) ×10(-2) vs (1.11 ± 0.72) ×10(-2) for BiP mRNA, 11.80(7.30-38.40)×10(-3) vs 1.27(1.02-4.18)×10(-3) for GRP94 mRNA, both P values <0.01] was significantly increased in macrophages in SpA patients.XBP1 mRNA was up-regulated [(12.70 ± 5.20) ×10(-3) vs (4.14 ± 2.56) ×10(-3), P < 0.01] in SpA group as well. UPR-regulated gene expression in SpA patients with HLA-B27 positive or HLA-B27 negative was similar.However, none of UPR-regulated genes showed different expression between the SpA group and RA group except for GADD34 mRNA[7.30(5.56-15.40)×10(-3) vs 21.30 (12.20-27.60) ×10(-3), P = 0.009].
Our data suggest that UPR possibly participates in the pathogenesis of SpA, although the relationship between HLA-B27 and UPR still needs further investigation.