Internal Medicine A, Bnai Zion Medical Center, Haifa 31048, P.O. Box 4940, Israel.
Inflammation. 2012 Apr;35(2):772-5. doi: 10.1007/s10753-011-9373-x.
Decreased levels of class II major histocompatibility complex (MHC) expression and impaired formation of immunological synapse by dendritic cells (DCs) of HLA-B27 transgenic rats have been recently demonstrated. The resulting dysfunction of DCs may be implicated in the pathogenesis of the HLA-B27-related disease in transgenic animals. The phenotype of DCs in patients with ankylosing spondylitis (AS) has not been evaluated. Monocyte-derived DCs (MDDCs) were grown from patients with active AS and age-matched healthy volunteers. Surface expression of HLA-DR, co-stimulation molecules CD80, CD86 and CD40, as well as CD83 was assessed by flow cytometry and compared between the groups under 3 conditions: in resting state, after stimulation by lipopolysaccharide (LPS) and after stimulation by LPS in the presence of etanercept, a soluble receptor of tumor necrosis factor α. Lower baseline expression of class II MHC molecules (HLA-DR) was observed by MDDCs grown from AS patients, as compared to healthy subjects. Post-stimulated levels of HLA-DR were comparable in both groups, suggesting greater up-regulation of class II MHC molecules by MDDCs from AS in response to LPS. No difference between groups in the levels of expression of co-stimulation molecules and CD83 was observed. Lower basic expression of class II MHC by the MDDCs grown from patients with AS may be associated with impaired regulation of their activity. Functional studies on DCs from patients with AS are needed to evaluate the integrity of their antigen-presenting function.
最近研究表明,HLA-B27 转基因大鼠树突状细胞(DC)表面 II 类主要组织相容性复合体(MHC)表达水平降低,免疫突触形成受损。由此导致的 DC 功能障碍可能与转基因动物中 HLA-B27 相关疾病的发病机制有关。尚未评估 HLA-B27 相关疾病患者中 DC 的表型。从活动期强直性脊柱炎(AS)患者和年龄匹配的健康志愿者中培养单核细胞来源的树突状细胞(MDDC)。通过流式细胞术评估 HLA-DR、共刺激分子 CD80、CD86 和 CD40 以及 CD83 的表面表达,并在 3 种条件下对两组进行比较:在静息状态下、经脂多糖(LPS)刺激后以及在存在依那西普(肿瘤坏死因子α可溶性受体)的情况下经 LPS 刺激后。与健康受试者相比,从 AS 患者中培养的 MDDC 表面 II 类 MHC 分子(HLA-DR)的基础表达水平较低。两组的刺激后 HLA-DR 水平相当,表明 AS 患者 MDDC 对 LPS 的反应性更强,从而上调 II 类 MHC 分子。两组共刺激分子和 CD83 的表达水平无差异。从 AS 患者中培养的 MDDC 基本表达 II 类 MHC 较低,可能与它们的活性调节受损有关。需要对 AS 患者的 DC 进行功能研究,以评估其抗原呈递功能的完整性。