Vasculitis-associated aberrant apolipoprotein A2 = VAP2 and SDF-1α in Kawasaki disease patients with coronary artery lesion.

BACKGROUND

Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects the coronary arteries. The most serious complications are coronary artery lesions (CALs), including arterial dilatation, aneurysm, and stenosis, which occur in approximately 25% of untreated patients. Intravenous immunoglobulin (IVIG) therapy markedly reduces the incidence of CALs to 2-3%; however, the underlying mechanisms of IVIG's therapeutic effects remain unclear. Recently, we identified a recombinant single-chain fragment of the variable region of human immunoglobulin G, termed VasSF, which significantly ameliorated vasculitis in SCG/Kj mice. The VasSF-binding protein of 24 kDa (VAP2) was subsequently identified as an aberrant form of apolipoprotein A2 (ApoA2) in the serum of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We investigated whether VAP2 and related ApoA2-derived molecules are associated with CAL formation in patients with KD.

MATERIALS AND

METHODS

Baseline demographic and clinical characteristics were evaluated in 34 patients with KD during the acute and convalescent phases. Among them, 14 (41.2%) were initial IVIG non-responders, and 10 (29.4%) developed CALs.

RESULTS AND DISCUSSION: Western blot analysis revealed that VAP2 and VasSF bound to 17-kDa serum molecules predominantly during the acute phase of KD. Notably, in the CAL group, VAP2 levels exhibited a significant correlation with stromal cell-derived factor-1α (SDF-1α) (r2 = 0.5700, p = 0.049) among 78 cytokines analyzed. VAP2 was identified as a target molecule of VasSF in association with SDF-1α in our study. Considering that VasSF has been proposed as a therapeutic candidate for ANCA-associated vasculitis through targeting of aberrant ApoA2, VasSF may likewise represent a potential therapeutic agent for KD.