Circulating B lymphocytes producing autoantibodies to endothelial cells play a role in the pathogenesis of Takayasu arteritis

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Abstract

Objective: Takayasu arteritis (TA) is an autoimmune 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 autoimmune 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-beta2 glycoprotein-I antibody (aβ2GPI), and anti-annexin V antibody (AAVA), were assayed by enzyme-linked immunosorbent assay (ELISA) in each participant. Results In vitro levels of AECA, ACA, aβ2GPI, 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; aβ2GPI: 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 aβ2GPI 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 aβ2GPI 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. © 2011 Society for Vascular Surgery.

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Wang, H., Ma, J., Wu, Q., Luo, X., Chen, Z., & Kou, L. (2011). Circulating B lymphocytes producing autoantibodies to endothelial cells play a role in the pathogenesis of Takayasu arteritis. Journal of Vascular Surgery, 53(1), 174–180. https://doi.org/10.1016/j.jvs.2010.06.173

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