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-alpha) and interferon-gamma (IFN-gamma).
Recurrent 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-alpha significantly increased AECA binding of both ROU (P < 0.005) and control samples (P < 0.0001), while IFN-gamma 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-alpha and decreased by IFN-gamma stimulation.
Healy
C M
CM
Department of Oral Medicine and Periodontology, London Hospital Medical College, UK.
Carvalho
D
D
Pearson
J D
JD
Thornhill
M H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000096:biosynthesis* / Q000187:drug effects; D001323:Autoantibodies / Q000096:biosynthesis* / Q000187:drug effects* / Q000378:metabolism*; D002648:Child; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D013281:Stomatitis, Aphthous / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D014409:Tumor Necrosis Factor-alpha; C087589:anti-endothelial cell antibody; D007371:Interferon-gamma