Raised anti-endothelial cell autoantibodies (AECA), but not anti-neutrophil cytoplasmic autoantibodies (ANCA), in recurrent oral ulceration: modulation of AECA binding by tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)

Abstract

SUMMARYRecurrent oral ulceration (ROU) is a common oral mucosal condition of unknown etiology. However, there is evidence to suggest that vasculitis may play a role. Here we investigate the presence in ROU of two autoantibodies associated with vasculitis, AECA and ANCA. AECA target as yet unidentified antigens on the endothelial cell surface and have been identified in patients with vasculitic disorders and inflammatory conditions with a vasculitic component. ANCA target specific neutrophil-associated proteins and are detected in specific vasculitic and chronic inflammatory disorders. AECA and ANCA levels were studied in 20 ROU patients and 20 controls. IgG AECA to the endothelial cell line ECV 304 were detected in 19 ROU patients and four controls. Levels were significantly raised in ROU both to ECV 304 (P < 0 . 000 05) and to human umbilical vein endothelial cells (HUVEC) (P < 0 . 005). Although levels were highest during episodes of ulceration, they were also raised between episodes. Stimulation of endothelial cells with TNF-® significantly increased AECA binding of both ROU (P < 0 . 005) and control samples (P < 0 . 0001), while IFN-°decreased binding (ROU P < 0 . 0001; controls P < 0 . 05). In contrast, ANCA were detected in only one patient and none of the controls. The presence of raised levels of AECA lends support to the hypothesis that a vasculitic process may underlie ROU. Moreover, these findings suggest that endothelial cell expression of AECA target antigens is increased by TNF-® and decreased by IFN-°stimulation.

Oxidant/antioxidant status in patients with recurrent aphthous stomatitis

“…Healy et al . observed the presence of raised levels of antiendothelial cell antibodies, lending support to the hypothesis that a vasculitic process may underlie RAS 14 . Some authors indicated that lymphokine‐induced killer activity was decreased in RAS compared with controls.…”

“…Several studies indicate that RAS is an immunopathological disorder. Numerous authors investigated immune status and response in patients with RAS 12–15 . Sistig et al .…”

Anti-endothelial cell antibodies (AECA) in patients with propylthiouracil (PTU)-induced ANCA positive vasculitis are associated with disease activity

“…In vasculitides, it was suggested that endothelium was not only the target of injury, but also an active participant of vasculitic damage [9]. Anti-endothelial cell antibodies (AECA) have been described in various autoimmune and vasculitic disorders [10][11][12][13][14][15][16][17][18]. They have been implicated in the pathogenesis of vascular injury common to these disorders.…”

Innate immune system is implicated in recurrent aphthous ulcer pathogenesis

“…Activation of the immune system in aphthous lesions and in peripheral blood was observed in RAU (3–13). Tissue‐specific autoimmunity is one of the most probable mechanisms of RAU development, with possible activation of Th1 lymphocyte profile of cytokine production (8, 14–17). There is also evidence suggesting that polymorphonuclear leukocytes (PMN) play a role in the pathogenesis of RAU (18–21).…”