Yu Hui-Chun, Lu Ming-Chi, Huang Kuang-Yung, Huang Hsien-Lu, Liu Su-Qin, Huang Hsien-Bin, Lai Ning-Sheng
Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan.
Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan.
Int J Mol Sci. 2015 Dec 29;17(1):46. doi: 10.3390/ijms17010046.
Human leukocytic antigen-B27 heavy chain (HLA-B27 HC) has the tendency to fold slowly, in turn gradually forming a homodimer, (B27-HC)₂ via a disulfide linkage to activate killer cells and T-helper 17 cells and inducing endoplasmic reticulum (ER) stress to trigger the IL-23/IL-17 axis for pro-inflammatory reactions. All these consequences lead to the pathogenesis of ankylosing spondylitis (AS). Sulfasalazine (SSA) is a common medication used for treatment of patients with AS. However, the effects of SSA treatment on (B27-HC)₂ formation and on suppression of IL-23/IL-17 axis of AS patients remain to be determined. In the current study, we examine the (B27-HC)₂ of peripheral blood mononuclear cells (PBMC), the mean grade of sarcoiliitis and lumbar spine Bath Ankylosing Spondylitis Radiology Index (BASRI) scores of 23 AS patients. The results indicated that AS patients without (B27-HC)₂ on PBMC showed the lower levels of mean grade of sarcoiliitis and the lumbar spine BASRI scores. In addition, after treatment with SSA for four months, the levels of (B27-HC)₂ on PBMCs were significantly reduced. Cytokines mRNA levels, including TNFα, IL-17A, IL-17F and IFNγ, were also significantly down-regulated in PBMCs. However, SSA treatment did not affect the levels of IL-23 and IL-23R mRNAs.
人类白细胞抗原-B27重链(HLA-B27 HC)有缓慢折叠的倾向,进而逐渐形成同型二聚体(B27-HC)₂,通过二硫键激活杀伤细胞和辅助性T细胞17,并诱导内质网(ER)应激以触发IL-23/IL-17轴引发促炎反应。所有这些后果导致强直性脊柱炎(AS)的发病机制。柳氮磺胺吡啶(SSA)是用于治疗AS患者的常用药物。然而,SSA治疗对(B27-HC)₂形成以及对AS患者IL-23/IL-17轴的抑制作用仍有待确定。在本研究中,我们检测了23例AS患者外周血单个核细胞(PBMC)中的(B27-HC)₂、骶髂关节炎平均分级以及腰椎巴斯强直性脊柱炎放射学指数(BASRI)评分。结果表明,PBMC中无(B27-HC)₂的AS患者骶髂关节炎平均分级和腰椎BASRI评分较低。此外,用SSA治疗四个月后,PBMC上(B27-HC)₂的水平显著降低。PBMC中细胞因子mRNA水平,包括TNFα、IL-17A、IL-17F和IFNγ也显著下调。然而,SSA治疗不影响IL-23和IL-23R mRNA的水平。