Abstract: Osteoprotegerin Serum Levels in Kawasaki Disease: An Additional Potential Marker in Predicting Children with Coronary Artery Involvement

Osteoprotegerin Serum Levels in Kawasaki Disease: An Additional Potential Marker in Predicting Children with Coronary Artery Involvement

GABRIELE SIMONINI, LAURA MASI, TERESA GIANI, ELISABETTA PISCITELLI, ROLANDO CIMAZ, SILVIA VIERUCCI, MARIA LUISA BRANDI, and FERNANDA FALCINI

ABSTRACT.

Objective. Emerging evidence from in vitro studies and mouse genetics attributes to osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, an important role in vascular biology. We evaluated serum levels of OPG in a group of children with Kawasaki disease (KD), before immunoglobulin (IVIG) infusion and at 3-month followup.

Methods. Fifty patients (38 boys, 20 girls, median age 3.6 yrs, range 4 mo–7.4 yrs) fulfilling criteria for the diagnosis of KD, 30 febrile controls with infectious diseases, 18 patients with juvenile systemic lupus erythematosus (JSLE), and 40 healthy controls were enrolled. All KD patients received IVIG treatment within the first 10 days of illness, and aspirin. Coronary artery abnormalities (CAA) were reported in 6 out of 58 patients; all were male and younger than 5 years. Serum OPG was measured by ELISA in patients with KD before IVIG and at 3-month followup (median time 3.2 mo, range 3–3.5).

Results. At baseline and at the 3-month followup, KD patients had significantly higher OPG serum levels than febrile controls (p < 0.001 and p < 0.004, respectively), JSLE patients (p < 0.0001), and healthy controls (p < 0.0001). At baseline, KD patients who developed CAA had higher OPG serum levels than those without CAA (p = 0.0001); this difference was not present at 3-month followup. The optimal OPG cutoff value of 123.2 pg/ml was a significant predictor for CAA, with a sensitivity of 100% (6/6), a specificity of 96% (50/52), and a positive predictive value of 75% (6/8).

Conclusion. High OPG levels might be the result of compensatory production during acute and subacute phases of KD. OPG assay might be an additional clinically useful marker to monitor and differentiate patients who develop, from those who do not develop, such coronary artery abnormalities. (J Rheumatol 2005;32:2233-8)

Key Indexing Terms:

OSTEOPROTEGERIN
KAWASAKI DISEASE
CORONARY ARTERY ABNORMALITIES

From the Department of Paediatrics — Rheumatology Unit, Department of Internal Medicine, and Department of Orthodontics, University of Florence, Florence; and Pediatrics, Istituti Clinici di Perfezionamento, Milano, Italy.

G. Simonini, MD, Department of Paediatrics — Rheumatology Unit; L. Masi, MD, Department of Internal Medicine; T. Giani, MD, Fellow in Pediatric Rheumatology; E. Piscitelli, BS, Department of Internal Medicine, University of Florence; R.G. Cimaz, MD, Dirigente Medico, Pediatrics, Istituti Clinici di Perfezionamento; S. Vierucci, DDS, PhD, Department of Orthodontics; M.L. Brandi, MD, Chief, Department of Internal Medicine; F. Falcini, MD, Associate Professor of Pediatrics, Department of Pediatrics, Rheumatology Unit, University of Florence.

Address reprint requests to Dr. G. Simonini, Department of Paediatrics– Rheumatology Unit, Via Pico della Mirandola 24, 50132 Firenze, Italy. E-mail: gabriele.simonini@unifi.it

Accepted for publication May 20, 2005.