Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
Scand J Rheumatol. 2012 Aug;41(4):267-74. doi: 10.3109/03009742.2012.664649. Epub 2012 Jun 1.
Reactive arthritis (ReA) is a sterile joint inflammation triggered by a remote infection and associated with human leucocyte antigen (HLA)-B27. Its pathogenesis is unknown, but abnormal response to microbial structures or endogenous inflammatory mediators may be involved. We studied responses in leucocyte signalling profiles in patients with previous ReA after a full recovery.
The study comprised 10 HLA-B27-positive healthy subjects with a history of Yersinia enterocolitica-triggered ReA (B27+ReA+) and 20 healthy reference subjects, of whom 10 carried HLA-B27 (B27+ReA-) and 10 did not (B27-ReA-). Phosphospecific fluorescent monoclonal antibodies and flow cytometry were used to determine activation of nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STATs) 1, 3, 5, and 6, and two mitogen-activated protein (MAP) kinases, p38 and extracellular signal-regulated kinase (ERK)1/2, in monocytes, lymphocytes, lymphocyte subsets, and neutrophils. B27+ReA+ and B27-ReA- whole-blood samples were incubated with Yersinia with or without infliximab to study the role of tumour necrosis factor (TNF) in lymphocyte subset activation. Samples of the three subject groups were studied using soluble bacterial or endogenous stimuli. Fluorescence levels were determined as relative fluorescence units (RFU) and the proportion of positively fluorescing cells.
The intracellular activation of circulating leucocytes in response to soluble stimuli was consistently comparable in B27+ReA+, B27+ReA-, and B27-ReA- subjects. Infliximab inhibited Yersinia-induced lymphocyte NF-κB phosphorylation similarly in B27+ReA+ and B27-ReA- groups.
ReA susceptibility is not reflected in leucocyte signalling profiles elicited by phlogistic stimuli. However, the possibility remains that aberrations occur in response to combinations of stimuli, such as those associated with leucocyte adhesion.
反应性关节炎（ReA）是一种由远处感染引发的无菌性关节炎症，与人类白细胞抗原（HLA）-B27 相关。其发病机制尚不清楚，但可能涉及对微生物结构或内源性炎症介质的异常反应。我们研究了先前患有肠耶尔森菌相关性反应性关节炎（B27+ReA+）且已完全康复的患者的白细胞信号谱反应。
该研究纳入了 10 名 HLA-B27 阳性、曾患肠耶尔森菌相关性反应性关节炎（B27+ReA+）的健康受试者和 20 名健康对照者，其中 10 名携带 HLA-B27（B27+ReA-），10 名不携带 HLA-B27（B27-ReA-）。使用磷酸化特异性荧光单克隆抗体和流式细胞术来确定单核细胞、淋巴细胞、淋巴细胞亚群和中性粒细胞中核因子 kappa B（NF-κB）、信号转导和转录激活因子（STAT）1、3、5 和 6 以及两种丝裂原活化蛋白（MAP）激酶 p38 和细胞外信号调节激酶（ERK）1/2 的激活。将 B27+ReA+和 B27-ReA-全血样本与耶尔森氏菌孵育，或与英夫利昔单抗孵育，以研究肿瘤坏死因子（TNF）在淋巴细胞亚群激活中的作用。使用可溶性细菌或内源性刺激物研究三组样本。荧光水平以相对荧光单位（RFU）和阳性荧光细胞的比例来确定。
对可溶性刺激物的循环白细胞的细胞内激活在 B27+ReA+、B27+ReA-和 B27-ReA-受试者中始终相似。英夫利昔单抗抑制 B27+ReA+和 B27-ReA-组耶尔森氏菌诱导的淋巴细胞 NF-κB 磷酸化的作用相似。
白细胞信号谱的反应性关节炎易感性不能反映由炎症刺激引起的白细胞信号谱。然而，仍有可能在白细胞黏附等组合刺激下出现异常。
