Bijl M, van Lopik T, Limburg P C, Spronk P E, Jaegers S M, Aarden L A, Smeenk R J, Kallenberg G G
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands.
J Autoimmun. 1998 Oct;11(5):457-63. doi: 10.1006/jaut.1998.0233.
Systemic lupus erythematosus (SLE) is characterized by generalized immune activation. Part of this might be explained by a decreased rate of apoptosis, possibly related to elevated levels of soluble Fas (sFas) which can inhibit Fas mediated apoptosis of lymphocytes. In order to substantiate the relation between levels of sFas and lymphocyte activation in SLE we monitored sFas levels, lymphocyte activation and disease activity in 25 SLE patients. SLEDAI scores were registered and sera were assayed for sFas levels by an enzyme-linked immunosorbent assay. Flow cytometry was used to monitor the state of activation of lymphocyte subsets. Eighteen healthy, age-matched volunteers served as controls. Soluble Fas levels were elevated in SLE patients (n=25) compared to healthy controls (n=18, P=0.002). Soluble Fas levels correlated with SLEDAI scores (r=0.45, P=0.02). Levels of sFas correlated with the percentages of activated B cells defined as CD20(+)CD38(+) cells (r=0.47, P=0.009). Percentages of CD20(+)CD38(+) cells were increased in quiescent SLE compared to healthy controls (P=0.003). The expression of activation markers on CD4(+) T lymphocytes (IL-2R, P=0.04; HLA-DR, P=0.01) and CD8(+) T lymphocytes (HLA-DR, P=0.007) was also increased in quiescent SLE compared to controls. Activation markers on all lymphocyte subsets tended to increase further during disease activity. No correlation was observed between percentages of activated T lymphocyte subsets and levels of sFas. In conclusion, soluble Fas levels are increased in SLE patients and correlate with disease activity as measured by the SLEDAI score and B and T cell subsets are activated even during quiescent SLE. Serum levels of sFas correlate with percentages of activated B cells but not with that of activated T cells.
系统性红斑狼疮（SLE）的特征是全身性免疫激活。部分原因可能是细胞凋亡率降低，这可能与可溶性Fas（sFas）水平升高有关，sFas可抑制Fas介导的淋巴细胞凋亡。为了证实SLE中sFas水平与淋巴细胞激活之间的关系，我们监测了25例SLE患者的sFas水平、淋巴细胞激活情况和疾病活动度。记录SLE疾病活动指数（SLEDAI）评分，并通过酶联免疫吸附测定法检测血清中的sFas水平。采用流式细胞术监测淋巴细胞亚群的激活状态。18名年龄匹配的健康志愿者作为对照。与健康对照组（n = 18，P = 0.002）相比，SLE患者（n = 25）的可溶性Fas水平升高。可溶性Fas水平与SLEDAI评分相关（r = 0.45，P = 0.02）。sFas水平与定义为CD20(+)CD38(+)细胞的活化B细胞百分比相关（r = 0.47，P = 0.009）。与健康对照组相比，静止期SLE患者中CD20(+)CD38(+)细胞的百分比增加（P = 0.003）。与对照组相比，静止期SLE患者中CD4(+) T淋巴细胞（IL-2R，P = 0.04；HLA-DR，P = 0.01）和CD8(+) T淋巴细胞（HLA-DR，P = 0.007）上激活标志物的表达也增加。在疾病活动期间，所有淋巴细胞亚群上的激活标志物倾向于进一步增加。未观察到活化T淋巴细胞亚群百分比与sFas水平之间的相关性。总之，SLE患者的可溶性Fas水平升高，且与SLEDAI评分所衡量的疾病活动度相关，即使在静止期SLE中，B和T细胞亚群也被激活。血清sFas水平与活化B细胞百分比相关，但与活化T细胞百分比无关。
