Histopathological Evaluation of Horse Serum-induced Immune Complex Vasculitis in Swine: Implication to Coronary Artery Lesions in Kawasaki Disease

Abstract

Immune complex (IC) vasculitis can be experimentally induced in animal models by intravenous injection of horse serum (HS), and the findings of HS-induced IC vasculitis in swine were very similar to that of Kawasaki disease (KD). The IC mechanism may be involved in the pathogenesis of vasculitis in KD. Here, we studied the two-dimensional (2D) echocardiographic and histopathological findings of acute, subacute, and healing phases of vasculitis induced by two different types of HS, and the reproducibility of IC vasculitis in swine. Our study group consisted of 24 pure-bred landrace male piglets of 1.5-3 months of age. They were divided into three HS groups (n=17), namely, Group A (n=8) receiving gamma globulin-free HS, and Group B (n=6) receiving donor herd HS, three doses at 5-day intervals, and Group C (n=3) that received only one dose of donor herd HS on Day 1, and the saline group (n=7) that received three doses of intravenous normal saline (NS) at 5-day intervals. The 2D echocardiography was performed every 3-4 days, and all piglets were killed for histopathological studies at different dates from Days 2 to Day 60. All the HS groups developed rashes and demonstrated significant dilation (54-150%) of coronary arteries in Groups A and B; when compared (p<0.02) with 9-53% dilation in Group C and the saline group. Histopathological changes of test groups were asymmetric coronary vasculitis in various stages, whereas none of the piglets in the control group developed vasculitis. No significant difference in the echocardiographic and histopathological findings was observed among the piglets that received two types of HS. HS can induce IC vasculitis in swine. The rashes and 2D echocardiographic and histopathological studies of the acute to healing phases showed close similarities with KD, and it is concluded that swine may serve as a unique experimental model for IC vasculitis and for various therapeutic trials.