Abstract 10512: Sialic Acid-rich Fc Having A Strong Anti-inflammatory Effect In Kawasaki Disease Model

Abstract

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery (CA) aneurysms. High-dose intravenous immunoglobulin (IVIG) is the most standard treatment. However, the problem with current high-dose IVIG therapy is that it is inefficient for both patients and cost because it contains ineffective parts and requires a high total dose. It has recently been reported that sialic acid in the fragment crystallizable (Fc) region has an anti-inflammatory effect. Hypothesis: In the KD model, a small amount of sialic acid-rich (SR-)Fc has an anti-inflammatory effect equivalent to that of high-dose IVIG. Methods: A Candida albicans cell wall extract (CAWE)-induced KD-like vasculitis model was established in DBA/2 mice. IgG, antigen-binding fragment (Fab), and Fc with 2g/kg/0.5ml, and IgG, SR-IgG, and SR-Fc with 0.2g/kg/0.5ml, and placebo 0.5ml were administered intraperitoneally 3 times every other day (n=5, respectively). Four weeks after treatment, we compared the incidence of CA inflammation between each group. Histological analysis was performed by using a quantified scoring system: grade 1; <20 cells /HPF, grade 2; <100cells/HPF, grade 3; >100cels/HPF, grade 4; distraction of elastic lamina, grade 5; neointimal proliferation. Results: All five mice in placebo group had the infiltration grade 3 or higher (100%), whereas none of the mice in IgG group had the infiltration (0%). In Fab group, three out of four had the infiltration (75%, one mouse died), whereas in Fc group, only one out of five had the infiltration (20%). In one-tenth dose IgG group, two out of four had the infiltration (50%, one mouse died), whereas in one-tenth dose SR-IgG and SR-Fc group, 20% or less of them had the infiltration (one out of five, zero out of five, respectively). Treatment with one-tenth dose SR-IgG and SR-Fc significantly suppressed CAWE-induced vasculitis ( p <0.05 and 0.01, respectively). Conclusions: It was shown that the immunoglobulin effect was mainly in the Fc region and one-tenth dose SR-Fc had an anti-inflammatory effect equivalent to that of high-dose IgG in a Candida -induced KD mouse model. One-tenth doses SR-Fc may be an alternative treatment to high-dose IVIG in KD patients.