期刊
JOURNAL OF VASCULAR SURGERY
卷 53, 期 1, 页码 174-180出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jvs.2010.06.173
关键词
-
资金
- Beijing Municipal Natural Science Foundation of China [7092026]
Objective: Takayasu arteritis (TA) is an autoiminune disease with an unclear etiology and pathophysiology. An antibody-mediated inflammatory response is a known feature of this disease, however, the role of circulating B-lymphocyte production of such antibodies is not known. The objective of this study is to characterize in vitro production of autohnmune antibodies by B-lymphocytes from patients with TA and to examine differences related to disease activity. Methods: Peripheral blood samples were taken from 72 patients with TA and 50 age-matched controls. Among the patients with TA, 42 had active disease while 31 had inactive disease. The Sharma modified criteria were used for diagnosis, and the National Institutes of Health criteria were used for TA activity assessment. Levels of autoantibodies in culture supernatant of circulating B-lymphocytes, including anti-endothelial cell antibody (AECA), anti-cardiolipin antibody (ACA), anti-beta(2) glycoprotein-I antibody (a beta(2)GPI), and anti-annexin V antibody (AAVA), were assayed by enzyme-linked imnaunosorbent assay (ELISA) in each participant. Results: In vitro levels of AECA, ACA, a beta(2)GPI, and AAVA from circulating B-lymphocytes were significantly increased in TA patients compared with controls (AECA: 0.6 +/- 0.36 vs 0.18 +/- 0.09, P < .001; ACA: 0.69 +/- 0.22 vs 0.54 +/- 0.13, P < .001; a beta(2)GPI: 0.99 +/- 0.19 vs 0.83 +/- 0.07, P < .001; AAVA: 0.62 +/- 0.26 vs 0.41 +/- 0.44, P < .001). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in active TA were higher than those in inactive TA (AECA: 0.85 +/- 0.29 vs 0.28 +/- 0.10, P < .001; ACA: 0.79 +/- 0.21 vs 0.56 +/- 0.15, P < .001; AAVA: 0.82 +/- 0.16 vs 0.36 +/- 0.06, P < .001). No difference was found in the in vitro level of a beta(2)GPI between active TA and inactive TA (1.01 +/- 0.17 vs 0.96 +/- 0.22, P = .115). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in inactive TA showed no statistic difference with those in controls (AECA: 0.28 +/- 0.10 vs 0.18 +/- 0.09, P = .096; ACA: 0.56 +/- 0.15 vs 0.54 +/- 0.13, P = .699; AAVA: 0.36 +/- 0.06 vs 0.41 +/- 0.44, P = .200). In vitro levels of a beta(2)GPI in inactive TA were higher than those in controls (0.96 +/- 0.22 vs 0.83 +/- 0.07, P < .001). Conclusions: This study characterizes in vitro production of autoantibodies by circulating B-lymphocytes from patients with TA. Differences in production from those with active versus inactive disease suggest that phenotypic alterations in this cell type may play an important role in pathogenesis. (J Vasc Surg 2011;53:174-80.) Clinical Relevance: Takayasu arteritis (TA) is a rare and autoimmune vasculitis with unclear pathogenesis. It has a high incidence in young females in Asia and Africa. The natural course of TA consists of an active phase and an inactive phase, which reflects the different inflammatory states of the arterial lesions. In the active phase, immunosuppressive and cytotoxic agents are usually used to control the inflammation development, release the symptoms, and restrict the extent of affected arteries. The treatment aim of the inactive phase is to avoid the disease activity, and if necessary, it is preferable to perform vascular reconstructive operations or endovascular interventions. It is very important that an effective therapy should be found to shorten the active phase of TA and lengthen the inactive stage, which can not only perform the surgery operation as early as possible, but also reduce inflammatory injury of arteries. In recent years, we have been working on the diagnosis and surgical treatment of TA. Our advance study, Circulation levels of acute phase proteins in patients with Takayasu arteritis published in J Vasc Surg 2010;51:700-6, contributed to the judgment of disease phase and showed the pivotal role of B cells and hiunoral immunity in TA. In this study, we found that circulating B-lymphocytes, producing autoantibodies to endothelial cells, played an important role in the pathogenesis of TA. It means that part/all of the circulating B-lymphocytes in TA patients can be activated and excrete autoantibodies to endothelial cells. If these abnormal circulating B-lymphocytes can be differentiated and separated from peripheral blood, the active phase could be shorten, the inactive stage could be lengthened, the disease could even be prevented. It might lessen the autoimmune injury of artery wall, lower the difficulty of the operation and shorten the time which TA patients should wait for vascular reconstructive operations or endovascular repair. Therefore, we regarded this study as a foundation of B-cell depletion therapy and/or immunological tolerance therapy for TA. The feasible therapeutic methods will be explored in our future research.
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