Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia
Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia
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DOI：
10.1210/jc.2002-021105
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发表时间：
2002-11-01
影响因子：
5.8
通讯作者：
Fukumoto, S
中科院分区：
文献类型：
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作者：
Yamazaki, Y;Okazaki, R;Fukumoto, S
X连锁低磷性软骨病、常染色体显性遗传性低磷血症/骨软化症和肿瘤引起的骨软化症中，常可观察到低磷性软骨病和血清1，25-二羟基维生素D水平过低。尽管新近发现的成纤维细胞生长因子-23参与了ADHR和TIO的发病机制，但缺乏临床证据表明成纤维细胞生长因子-23的作用。我们先前已经证明了在精氨酸(179)和丝氨酸(180)之间切割成纤维细胞生长因子-23，并且这个过程取消了成纤维细胞生长因子-23诱导低磷血症的生物活性。因此，利用两种需要同时存在人成纤维细胞生长因子-23的N端和C-端部分的单抗，建立了检测具有生物活性的完整人成纤维细胞生长因子-23的夹心ELISA法。健康成人血清成纤维细胞生长因子-23水平在8.2~54.3 ng/L之间，而甲状腺肿大患者血清中成纤维细胞生长因子-23水平高于200 ng/L，切除肿瘤后1h内升高的血清成纤维细胞生长因子-23水平恢复到正常水平，血清1，25-二羟基维生素D和磷酸盐水平升高，24，25-二羟基维生素D水平下降。此外，大多数XLH型患者的血清FGF23水平也明显升高。血清成纤维细胞生长因子-23水平的升高可能不仅导致了低磷血症的发生，也可能导致了XLH型低磷血症的发生。
Hypophosphatemic rickets/osteomalacia with inappropriately low serum 1,25-dihidroxyvitamin D level is commonly observed in X-linked hypophosphatemic rickets/osteomalacia, autosomal dominant hypophosphatemic rickets/osteomalacia and tumor-induced osteomalacia. Although the involvement of a newly identified factor, FGF-23, in the pathogenesis of ADHR and TIO has been suggested, clinical evidence indicating the role of FGF-23 has been lacking. We have previously shown that FGF-23 is cleaved between Arg(179) and Ser(180), and this processing abolished biological activity of FGF-23 to induce hypophosphatemia. Therefore, sandwich ELISA for biologically active intact human FGF-23 was developed using two kinds of monoclonal antibodies that requires the simultaneous presence of both the N-terminal and C-terminal portion of FGF-23. The serum levels of FGF-23 in healthy adults were measurable and ranged from 8.2 to 54.3 ng/L. In contrast, those in a patient with TIO were over 200 ng/L. After the resection of the responsible tumor, the elevated FGF-23 level returned to normal level within 1 h. The increase of serum concentrations of 1,25-dihidroxyvitamin D and phosphate, and the decrease of serum 24,25-dihydroxyvitamin D followed the change of FGF-23. In addition, the elevated serum FGF-23 levels were demonstrated in most patients with XLH. It is likely that increased serum level of FGF-23 contributes to the development of hypophosphatemia not only in TIO but also in XLH.