Christensson Marta, Pettersson Erna, Eneslätt Kjell, Christensson Birger, Bratt Johan, Rantapää-Dahlqvist Solbritt, Sundqvist Karl-Gösta
Department of Clinical Immunology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
J Clin Immunol. 2002 Jul;22(4):220-7. doi: 10.1023/a:1016040925295.
The role of the Fas/FasL system in ANCA-associated vasculitis is unclear. We therefore assessed levels of soluble Fas (sFas) in sera and Fas expression on mononuclear cells from patients with ANCA-positive vasculitis and compared the results with those found in other rheumatic diseases. Serum levels of sFas were determined by ELISA. The ANCA-positive vasculitis patients studied included 29 at onset, 17 in first remission while on therapy, and 12 in quiescence. For comparison, 10 patients with Sjogren's syndrome (SS), 14 patients with systemic lupus erythematosus (SLE), 29 patients with rheumatoid arthritis (RA), 7 patients on dialysis (DP), and 26 healthy controls (HC) were studied. In addition, Fas expression in mononuclear cells was examined at the mRNA level using reverse transcriptase (RT)-PCR in 6 vasculitis patients at onset and in first remission. The expression of CD95 on the surface of leukocytes was determined by flow cytometry in 6 vasculitis patients at onset of the disease, in 6 patients in clinical remission, and in 6 HC. Expression of Fas and FasL in renal biopsy specimens was studied using immunohistochemistry. Patients with vasculitis had high sFas levels irrespective of disease phase. Both vasculitis patients and patients with RA and SLE had significantly increased sFas levels compared with healthy controls. All patient groups had sFas levels, which correlated with raised serum creatinine values. However, the sFas levels in vasculitis patients in first remission and in quiescence were increased despite a lower serum creatinine compared with onset. Some of the vasculitis patients showed an increased mRNA expression of Fas in mononuclear cells after treatment, suggesting that Fas production fluctuates with the intensity of the disease. The expression of CD95 on leukocytes was slightly decreased in vasculitis patients compared to healthy controls. No alterations of Fas and FasL expression were seen in renal biopsy specimens. These results show that ANCA-positive vasculitis patients have high sFas levels and that the levels remain elevated even in clinical remission. The findings indicate that perturbations in the Fas/Fas ligand system may play a role in the disease process in ANCA vasculitis.
Fas/FasL系统在抗中性粒细胞胞浆抗体（ANCA）相关血管炎中的作用尚不清楚。因此，我们评估了ANCA阳性血管炎患者血清中可溶性Fas（sFas）水平以及单核细胞上Fas的表达，并将结果与其他风湿性疾病患者进行比较。采用酶联免疫吸附测定（ELISA）法测定血清sFas水平。研究的ANCA阳性血管炎患者包括29例发病期患者、17例治疗期间首次缓解患者和12例病情静止患者。作为对照，研究了10例干燥综合征（SS）患者、14例系统性红斑狼疮（SLE）患者、29例类风湿关节炎（RA）患者、7例透析患者（DP）和26例健康对照者（HC）。此外，采用逆转录酶（RT）-PCR法在mRNA水平检测了6例发病期和首次缓解期血管炎患者单核细胞中Fas的表达。采用流式细胞术测定6例疾病发作期血管炎患者、6例临床缓解期患者和6例健康对照者白细胞表面CD95的表达。采用免疫组织化学法研究肾活检标本中Fas和FasL的表达。血管炎患者无论处于疾病的哪个阶段，其sFas水平均较高。与健康对照者相比，血管炎患者以及RA和SLE患者的sFas水平均显著升高。所有患者组的sFas水平均与血清肌酐值升高相关。然而，与发病期相比，首次缓解期和病情静止期血管炎患者的sFas水平虽血清肌酐较低但仍升高。部分血管炎患者治疗后单核细胞中Fas的mRNA表达增加，提示Fas的产生随疾病强度而波动。与健康对照者相比，血管炎患者白细胞上CD95的表达略有降低。肾活检标本中未观察到Fas和FasL表达的改变。这些结果表明，ANCA阳性血管炎患者的sFas水平较高，且即使在临床缓解期该水平仍保持升高。研究结果表明，Fas/Fas配体系统的紊乱可能在ANCA血管炎的疾病进程中起作用。
