Introduction: We identified 3 linked KD vasculopathic processes: acute self-limiting necrotizing arteritis, subacute/chronic (SA/C) arteritis and luminal myofibroblastic proliferation, most critically affecting the coronary arteries (CA). SA/C arteritis (lymphocytes, eosinophils, plasma cells) was not previously recognized, and patients with persistent coronary artery aneurysms do not currently receive immunomodulatory therapy after the initial febrile illness.
Hypotheses: SA/C arteritis in KD CA is a process of dysregulated innate and adaptive immune responses, and markers of inflammation can be detected in the sera of KD patients with persistently inflamed CAs.
Methods: RNA was isolated from paraffin-embedded CA tissues, and real-time RT-PCR arrays performed on samples passing quality control assays. RNA from KD CA with persistent subacute/chronic arteritis (n=7, 5 mo-several yrs after onset, median age=3 yr) and from CA of childhood controls (n=7, median age=10 mo) was assayed, and dysregulated genes determined (>1.5 fold change and q value <0.05). To identify if dysregulated immune markers were detected in sera of KD children with persistent CA aneurysms, ELISA cytokine array for 400 proteins was performed on sera from 4 KD patients with persistently abnormal CA echocardiograms who were otherwise asymptomatic (3-5 yrs after onset, median age 5 yrs) and 4 age/gender matched healthy childhood controls (median age 5 yrs).
Results: Ten interferon response genes and 9 Th1/Th2 response genes were upregulated in chronic KD arteritis tissues. ELISA revealed ~40 proteins with at least tenfold dysregulation in sera of KD children with persisting aneurysms compared to matched controls (q-values=0.07), while serum C-reactive protein levels were not different in the 2 groups.
Conclusions: Evidence of dysregulated immune responses can be detected in KD CA tissues months to years after onset in patients with persistent CA disease. In addition, we identified many candidate immune biomarkers of chronic KD arteritis. An immune biomarker panel would be useful to identify and monitor patients with persistent coronary arteritis in potential future clinical trials of immunomodulatory therapies for such patients.