Oxidized haemoglobin as antigenic target of cell-mediated immune reactions in patients with carotid atherosclerosis

Atherosclerosis is a chronic inflammatory disease in which immune responses play a crucial role. Evidence exist demonstrating the involvement of autoimmune mechanisms in atherogenesis. Our aim in this study was to evaluate the possible role of human oxidized haemoglobin (Hb) as antigenic target of cell-mediated immune reactions in carotid atherosclerosis. PBMC from 44 patients and 24 healthy subjects, and T lymphocytes isolated from 9 carotid atherosclerotic plaques were tested by cell proliferation assay and by ELISA for cytokine production in response to oxidized Hb. This molecule induced a proliferative response in 21 of 44 (48%) patientsʹ PBMC samples, in 12 of 24 (50%) healthy subjectsʹ PBMC samples and in 2 of 9 (22%) infiltrating T lymphocyte samples. Cells from patients proliferating in response to oxidized Hb showed high levels of the pro-inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Our findings implicate oxidized Hb as a possible antigenic target of cell-mediated immune responses contributing to inflammation in the pathogenesis of carotid atherosclerosis.