Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children

被引：39

作者：

Hathout, Yetrib ^{[1
]}

Conklin, Laurie S. ^{[1
]}

Seol, Haeri ^{[1
]}

Gordish-Dressman, Heather ^{[1
]}

Brown, Kristy J. ^{[1
]}

Morgenroth, Lauren P. ^{[1
]}

Nagaraju, Kanneboyina ^{[1
]}

Heier, Christopher R. ^{[1
]}

Damsker, Jesse M. ^{[1
]}

van den Anker, John N.

Henricson, Erik ^{[2
]}

Clemens, Paula R. ^{[3
]}

Mah, Jean K. ^{[4
]}

McDonald, Craig ^{[2
]}

Hoffman, Eric P. ^{[1
]}

机构：

[1] Childrens Natl Hlth Syst, Res Ctr Genet Med, Washington, DC 20010 USA

[2] Univ Calif, Davis Sch Med, Dept Phys Med & Rehabil, Davis, CA 95618 USA

[3] Univ Pittsburgh, Dept Neurol, Dept Vet Affairs Med Ctr, Neurol Serv, Pittsburgh, PA 15260 USA

[4] Alberta Childrens Prov Gen Hosp, Dept Pediat, Calgary, AB T3B 6A8, Canada

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

DUCHENNE MUSCULAR-DYSTROPHY; PRACTICAL GUIDE; DENDRITIC CELLS; BONE TURNOVER; GROWTH; PREDNISONE; MANAGEMENT; ARTHRITIS; THERAPY; OSTEOPOROSIS;

D O I：

10.1038/srep31727

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes.

引用

页数：10

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