Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy.
Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy.
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DOI：
10.1007/s10545-010-9175-6
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发表时间：
2010-12
影响因子：
4.2
通讯作者：
Mistry, Pramod K.
中科院分区：
文献类型：
--
作者：
Stein, Philip;Malhotra, Advitya;Haims, Andrew;Pastores, Gregory M.;Mistry, Pramod K.
局灶性脾损害(FSL)发生在高谢病I型(GD1)，但其临床意义尚不清楚。以前的研究估计，在GD1患者中，FSL的患病率为4%(儿童)到33%(成人)，并报告了与脾肿大有关。我们测试了FSL的存在与巨噬细胞导向的酶替代疗法(ERT)的次优反应相关的假设。此外，我们还调查了FSL是否与GD1的其他表型特征相关。对239例脾功能正常的GD1患者行常规MRI检查，对其脾实质进行评估。FSL患病率为18.4%(44/239)。在平均3.5年的ERT治疗后，FSL患者的血小板反应性较差(80,700±9,600至90,100±7,200/mm~3，P=0.2)，而非FSL患者的血小板反应较强：108,600±5,670至150,200±6,710/mm~3，P<；0.001。与无FSL的患者相比，有FSL的患者有更严重的血小板减少(血小板计数：83,700±8,800比112,100±4,200/mm~3，P=0.004)，术前脾肿大的频率更高，术后的脾更大(8.5±0.77比4.8±0.25×正常，P=0.001)。此外，与非FSL患者相比，FSL患者的骨坏死发生率更高(38%比20.7%，P=0.026)。FSL似乎是ERT反应的决定因素，建议比较新出现的治疗GD1的相对疗效的研究应该针对这一因素进行调整。此外，FSL的发生与GD1更严重的表现相吻合，如无血管性骨坏死。
Focal splenic lesions (FSL) occur in Gaucher disease type I (GD1), but their clinical significance is not known. Previous studies estimated the prevalence of FSL at 4% (pediatric) to 33% (adult) of GD1 patients and reported an association with splenomegaly. We tested the hypothesis that the presence of FSL is associated with suboptimal response to macrophage-directed enzyme replacement therapy (ERT). Additionally we investigated whether FSL were associated with other phenotypic features of GD1. The splenic parenchyma was assessed by MRI performed for routine evaluation of GD1 in 239 consecutive GD1 patients with intact spleens. The prevalence of FSL was 18.4% (44/239). Following a mean of 3.5 years of ERT, platelet response was inferior among patients with FSL (80,700± 9,600 to 90,100±7,200/mm3, P=0.2) compared to patients without FSL in whom there was a robust platelet response: 108,600±5,670 to 150,200±6,710/mm3, P<0.001. Compared to patients without FSL, patients harboring FSL had worse thrombocytopenia (platelet count: 83,700±8,800 vs. 112,100±4,200/mm3, P=0.004), greater frequency of pre-ERT splenomegaly, and greater post-ERT splenomegaly (8.5±0.77 vs. 4.8±0.25× normal, P<0.001). Additionally, the prevalence of osteonecrosis was higher among patients with FSL compared to patients without FSL (38 vs. 20.7%, P=0.026). FSL appear to be a determinant of response to ERT, suggesting studies comparing relative efficacy of newly emerging therapies for GD1 should adjust for this factor. Moreover, occurrences of FSL coincide with more severe manifestations of GD1 such as avascular osteonecrosis.
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影响因子：
19.7
作者：
HILL, SC;REINIG, JW;SHAWKER, TH
通讯作者：
SHAWKER, TH
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通讯作者：
Zimran, A
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作者：
ZIMRAN, A;ELSTEIN, D;HOROWITZ, M
通讯作者：
HOROWITZ, M