Department of Gynecologic Endocrinology and Reproductive Medicine, Innsbruck Medical University, Innsbruck, Austria.
J Clin Endocrinol Metab. 2011 Jan;96(1):E233-41. doi: 10.1210/jc.2010-1532. Epub 2010 Oct 27.
Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated.
Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis.
This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center.
Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded.
Blood was collected preoperatively.
Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis.
We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P < 0.02). Analysis of specific allele products using nano-scale liquid chromatography-electrospray ionization-mass spectrometry indicated that it was the GC2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion.
We speculate that the inability to sufficiently activate macrophages' phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.
之前的研究表明,患有子宫内膜异位症的女性存在炎症反应缺陷。具体的免疫缺陷尚未完全阐明。
我们的目的是确定血清中蛋白表达的差异,这些差异可能有助于阐明子宫内膜异位症的病理生理学。
这项 2003 年至 2005 年期间在一所大学医学中心进行的、针对接受腹腔镜手术的女性的横断面研究。
包括年龄在 18-49 岁之间、因疼痛和/或不孕或选择性输卵管结扎而接受手术的同意患者。排除患有急性或慢性疾病的患者。
术前采集血液。
使用二维差异凝胶电泳对血清进行蛋白质组分析。
我们发现 25 个蛋白斑点的丰度在子宫内膜异位症患者和对照组之间存在显著差异,包括急性期蛋白和补体成分。与对照组相比,所有子宫内膜异位症组中维生素 D 结合蛋白的丰度均高出约 3 倍(P <0.02)。使用纳升液相色谱-电喷雾电离-质谱分析特定等位基因产物表明,在患有子宫内膜异位症的女性的血清组和单个验证样本中,GC2 等位基因产物的浓度更高(P =0.006)。与 GC1 等位基因产物不同,GC*2 等位基因产物不易转化为有效的巨噬细胞因子(Gc 蛋白衍生的巨噬细胞激活因子)。
我们推测,携带 GC*2 多态性(在子宫内膜异位症中更为常见)的个体中,巨噬细胞吞噬功能的激活能力不足,可能允许子宫内膜组织在腹腔内植入。需要进一步研究,评估特定的维生素 D 结合蛋白多态性作为更大人群中子宫内膜异位症的风险因素。