Short stature in partially corrected X-linked severe combined immunodeficiency--suboptimal response to growth hormone.
Short stature in partially corrected X-linked severe combined immunodeficiency--suboptimal response to growth hormone.
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DOI：
10.1515/jpem.2008.21.11.1057
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Malech HL
中科院分区：
文献类型：
--
作者：
De Ravin SS;Shum E;Zarember KA;Rezvani G;Rosenfeld RG;Stratakis CA;Malech HL
X连锁严重联合免疫缺陷是由白介素2、白介素4、白介素7、白介素9、白介素15和白介素21(1)受体传递信号所需的共同细胞因子受体γ链(γc)缺陷引起的。在单倍体相合的骨髓移植治疗XSCID后，大多数患者实现了部分重建，通常仅限于T淋巴细胞。许多部分矫正的患者表现出极矮的身材(<；5%)。已有报道表明γc参与生长激素(GH)受体信号转导，因此XSCID的严重生长障碍可能与潜在的γc缺陷有关。[目的]探讨3例XSCID患儿生长激素/胰岛素样生长因子-1(GH/IGF-1)轴的变化及部分免疫重建对生长发育不良的影响。皮下注射重组生长激素5天，测定注射前、注射后第5天和第8天的血清IGF-1水平。生长激素刺激后，3例患者的生长轴IGF-1产生均显著减少。这些数据表明，这些部分矫正的严重矮小的XSCID患者的GH/IGF1轴严重受损，并支持先前的研究，即潜在的γc缺陷可能与XSCID的严重生长障碍有关。这支持了γc缺陷在XSCID极短身高中的作用，并增加了重组IGF1治疗绕过这一缺陷的可能性。
X-linked severe combined immunodeficiency (XSCID) results from defects in the common cytokine receptor γ chain (γc) required for signaling by receptors for interleukin (IL)-2, -4, -7, -9, -15, and -21 (1). Following haploidentical bone marrow transplant without myelo-conditioning for XSCID, most patients achieve partial reconstitution(2) often limited to T lymphocytes. Many partially corrected patients manifest extreme short stature (<5th percentile). Previous reports have implicated γc in growth hormone (GH) receptor signaling, thus severe growth failure in XSCID may be related to the underlying γc defect. To evaluate the GH/insulin-like growth factor (IGF-1) axes in 3 children with XSCID and partial immune reconstitution with profound growth failure. The IGF-1 generation test was performed by administering recombinant GH subcutaneously for 5 days, and measuring serum levels for IGF-1 before GH injection, and on days 5 and 8. Study of the somatotropic axis revealed profoundly diminished IGF-1 production following rGH challenge in all 3 patients. The data indicate that the GH/IGF-1 axes in these partially corrected XSCID patients with severe short stature is profoundly impaired, and supports previous studies suggesting that the underlying γc defect may contribute to the severe growth failure in XSCID. This supports a role for defective γc in extreme short stature of XSCID, and raises the possibility of recombinant IGF-1 treatment to bypass this defect.