Contribution of Myeloperoxidase to Coronary Artery Vasculitis Associated with MPO-ANCA Production Induced by Candida albicans -Derived Substances

Abstract

The role of myeloperoxidase (MPO) for vasculitis formation accompanied with the production of MPO-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) was analyzed using wild and MPO-deficient mice. MPO-ANCA levels in sera of wild type C57BL/6 mice with vasculitis particularly in the coronary arteries induced by injection of (Candida albicans-derived substances (CADS) increased. The MPO-ANCA titers in sera were significantly higher in vasculitis-positive mice than in vasculitis-negative mice, indicating that MPO-ANCA was closely associated with vasculitis formation. However, the increase of MPO-ANCA titers observed in sera of wild C57BL/6 mice were strongly suppressed in MPO-deficient C57BL/6 mice, accompanied with prevention of vasculitis formation. These results show that MPO acted as an antigen for MPO-ANCA production by CADS injection and was followed by the vasculitis formation. Vasculitis did develop in a few MPO-deficient mice, though the incidence of vasculitis was much lower in MPO-deficient mice than in C57BL/6 mice. This result suggests that other antigens structurally similar to MPO may also exist.