15 The role of intracisternal deposited igg in the pathogenesis of neuropsychiatric symptoms of systemic lupus erythematosus

Background and Aims Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by high levels of autoantibodies and multi-organ tissue damage including damage of the central system. Nerve system disease in SLE includes neurologic and psychiatric events, collectively termed neuropsychiatric SLE (NPSLE). Currently, the pathogenesis of NPSLE is unclear. We investigated pathogenesis of NPSLE in this study. Methods To understand the pathogenesis of NPSLE, we analysed the medical records of 1131 patients with SLE, and conducted experiments by using lupus-prone mice and mice with intracisternal injections of lupus serum containing high level of autoantibody and mice with gene deficiency. Results There are 59 patients with NPSLE clinical manifestation including headaches, seizure disorder, cognitive dysfunction, cerebrovascular disease, etc. MRI examination in 14 patients with NPSLE indicates 50% normal and 50% abnormal signals. Lupus-prone mice spontaneously develop meningitis. Meningitis was developed in normal mice with intracisternal injection of lupus serum but not healthy serum; IgG is a major contributor in this meningitis. Monocyte/macrophage, complement and selectin are involved in the development of meningitis induced by lupus serum. This meningitis is dependent on dose of IgG but not associated with kinds of autoantibodies and systemic disease activity. Severity of meningitis induced by lupus serum IgG was significantly reduced in TNF deficient mice compared to wild mice. Conclusions The deposited IgG or IgG contained immune complex in brain tissue exerts an important role in the pathogenesis of meningitis. This finding will promote development of effective therapeutic strategy to patients with NPSLE.