Osteoprotegerin serum levels in Kawasaki disease: an additional potential marker in predicting children with coronary artery involvement.
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).


CONCLUSIONS
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.
Simonini
Gabriele
G
Department of Paediatrics, Rheumatology Unit, University of Florence, Florence, Italy. gabriele.simonini@unifi.it
Masi
Laura
L
Giani
Teresa
T
Piscitelli
Elisabetta
E
Cimaz
Rolando
R
Vierucci
Silvia
S
Brandi
Maria Luisa
ML
Falcini
Fernanda
F
D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D053244:Osteoprotegerin; D011237:Predictive Value of Tests; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D012680:Sensitivity and Specificity
D015415:Biomarkers; D006023:Glycoproteins; D016756:Immunoglobulins, Intravenous; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse