Activation of C3 promotes experimental autoimmune thyroiditis in C5 deficient female A/J mice. (93.15)

Abstract Clinical studies suggest that activated C3, an early product of complement activation which can be triggered by infectious or environmental agents, is associated with more severe autoimmune thyroiditis, but few studies have illuminated mechanisms responsible for this observation. Animal models show that the severity of autoimmune thyroiditis is associated with late complement components, such as C5, and genetic susceptibility at the I-Ak sublocus. To elucidate additional complement-mediated effects on autoimmune thyroiditis we induced thyroiditis in I-Ak positive CBA/J and C5-deficient A/J mice with and without cobra venom factor which would activate the alternative complement pathway. A/J mice as a group developed less severe thyroiditis than CBA/J mice (p < 0.001). Surprisingly, female A/J mice developed less thyroiditis than males (p < 0.01) and had lower serum C3 levels (p < 0.05) during thyroiditis induction while thyroiditis and C3 in male A/J was not different from CBA/J mice. Cobra venom factor increased serum C3 levels, TNFα and thyroiditis but not intra-thyroid C3 deposition in A/J females suggesting that systemic complement activation increased thyroiditis in these mice. Our studies suggest that C3 activation promotes experimental thyroiditis in less susceptible A/J females, and may reveal one mechanism by which infections or other environmental agents promote autoimmune thyroiditis in patients.