Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


ROLE of FGF23 IN Kawasaki Disease (KD): A Possible Predictor of Subclinical Atherosclerosis

Falcini1,  F., Masi2,  L., Leoncini2,  G., Franceschelli2,  F., Vitale3,  A., Capannini1,  S., La Torre3,  F.

Department of BioMedicine, Division of Rheumatology, Transition Unit, University of Florence, Firenze, Italy,
Department of Internal Medicine, Metabolic Bone Disease Unit, University of Florence, Firenze, Italy,
Department of Paediatrics, Rheumatology Unit, University of Messina, Messina, Italy,
University, Firenze, Italy

Purpose:

Vascular endothelial damage is a key event in KD, a systemic necrotizing vasculitis complicated by widespread long term arterial dysfunction. Endothelial damage is crucial in the process of atherogenesis as intimal lesions can become atherosclerotic plaques. KD pts seem to be at risk of early subclinical atherosclerosis. The relationship between inflammation and calcification provides evidence that inflammation is a potent initiator of vascular damage in atherosclerosis. Phosphatonins are new hormones involved in phosphate homeostasis and bone mineralization. FGF23, the master phosphatonin, acts through FGF receptor 1 present in several tissues including vasculature and heart. The fgf23 knockout mice develop ectopic calcification, vascular and heart damage.

Aims:

1.To evaluate the serum level of intact FGF23 in KD pts. 2. To screen all patients for mutation in FGF23 gene.

Method:

70 pts (47 M, 23 F, mean age 38.6 ± 26.65 mths) with history of KD were enrolled in the study. 14/70 had CAA. At study entry, lipid profile (total cholesterol, HDL, LDL, triglycerides) was evaluated. Forty age and sex matched healthy children acted as controls.

The serum intact FGF23 concentration was measured, using an ELISA assay (Immunotopics Inc. San Clemente, CA, USA). Genomic DNA was extracted from peripheral blood and the three FGF23 exons, including the intron-exon boundary regions, were PCR-amplified. Purification products were analyzed on ABI Prism 100 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). The obtained sequences were compared to wild type reference sequence of the FGF23 gene published on Genbank Database (NT_009759).

Results:

FGF23 serum levels were higher in KD pts than in controls (23 ± 4.14 vs 10.3±3 pg/ml; p=0.004). DNA analysis showed new intronic C insertion between -36 and -37 nucleotides close exon2, and polymorphism C>T in exon3. Interestingly, all CAA pts had FGF23 serum levels significantly higher than those without coronary disease (Mann-Whitney U test: DF: 2.5 p=0.6); 10/14 had the new C insertion and 4/14 polymorphism C>T. Conversely, C insertion was detected only in 4/56 pts without CAA and none had polymorphism C>T. CAA pts had higher cholesterol level, in particular significant LDL in comparison to those without.

Conclusion:

This is the first study of serum FGF23 levels and FGF23 gene polymorphism in pts with history of KD. Our preliminary results point to circulating FGF23 values and FGF23 gene polymorphism as two potential predictors of early atherosclerosis in KD pts. The high amount of serum FGF23 may be in part responsible of the pathogenesis of vascular and heart damage and its complications in KD.

To cite this abstract, please use the following information:
Falcini, F., Masi, L., Leoncini, G., Franceschelli, F., Vitale, A., Capannini, S., et al; ROLE of FGF23 IN Kawasaki Disease (KD): A Possible Predictor of Subclinical Atherosclerosis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1538
DOI: 10.1002/art.26612

Abstract Supplement

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