摘要
全肺灌洗(WLL)是目前肺泡蛋白沉积症(PAP)的标准治疗方法。然而,一些巴氏病患者对WLL反应不佳或经常需要WLL。本文报告一例自身免疫性巴氏淋巴瘤,经3次治疗10个月后仍有持续性。
Plasmapheresis with ten 1.5-L plasma exchanges was performed, which lowered the serum granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody level from 250 μg·mL-1156μg·毫升-1但没有改善呼吸障碍。需要进一步的WLL治疗和暂时有效。血清GM-CSF自身抗体水平逐渐下降,达到56英克·mL-180 weeks after completion of plasmapheresis. However, this decrease was not accompanied by clinical improvement and the patient required additional WLL therapy.
结果证实,血浆置换导致的血清粒细胞-巨噬细胞集落刺激因子自身抗体水平的微小降低并不能反映在肺泡蛋白沉积症患者肺部疾病严重程度的临床改善中。
肺泡蛋白沉积症(PAP)是一种罕见的综合征可导致呼吸衰竭空域内,其特征在于表面活性剂的脂质和蛋白质的积累。的综合征,自身免疫性PAP的最常见的形式中,特别是与高水平的中和粒细胞 - 巨噬细胞集落刺激因子(GM-CSF)的自身抗体的由消除GM-CSF生物活性认为介导发病相关的体内而损害在肺泡巨噬细胞的GM-CSF依赖的表面活性剂分解代谢和减少肺表面活性物质的间隙1。全肺灌洗(WLL)是目前治疗自身免疫性巴氏病的标准护理方法,可有效地清除体内积聚的表面活性物质,对大多数患者有效2。然而,在一些病人的WLL无效,尽管重复WLL治疗1。理论上,血浆置换可有效去除想必致病中和GM-CSF自身抗体和此方法已在一个患者进行了描述,在其中血浆导致改善症状,血液中的氧饱和度和肺的放射线照相外观3。根据后一份报告,本作者承担了重复使用血浆置换治疗自身免疫性PAP病人谁是响应WLL不佳。
案例报告
一个40年生的人基于肺活检接收自身免疫性PAP的诊断在2004年,高清晰度的计算机断层摄影胸部(CT),和血清中和升高的GM-CSF自身抗体水平。Progressive respiratory failure developed and the patient was treated with WLL in October 2004. A total of 30 L of normal saline was used for each lung and was combined with mechanical chest percussion during infusion and drainage to improve the physical removal of the accumulated alveolar surfactant. Lung function improved, as evidenced by a change in the gas exchange after the WLL therapy. The therapeutic effects of WLL were transient and lasted only a few months, in contrast to most PAP patients treated by WLL at our centre using the same technique4。Respiratory impairment progressed and WLL therapy was repeated 4 and 10 months later (February and August 2005), again with only minimal and transient improvement. At this point, the patient was regarded as a poorly responsive to WLL therapy and other therapies were considered.
获得来自帕维亚医院伦理委员会(意大利帕维亚)批准后,患者的治疗是试图通过去除GM-CSF自身抗体的血浆使用,如最近描述3。The patient received 10 treatment sessions during February and March of 2006, each of which involved a plasma exchange volume of 1.5 L. This relatively low-intensity regimen was chosen to minimise the potential plasmapheresis complications, represented by a slight increase of infections due to the loss of immunoglobulins, and the induction of a pro-thrombotic state. Plasmapheresis decreased the serum GM-CSF autoantibody level from an initial value of 250 μg·mL-1to 130 μg·mL-1第三届会议后;however, the level did not decrease further despite seven additional sessions and was 153 μg·mL-1after a total of 10 sessions (fig. 1⇓)。重要的是,这种治疗并没有改善病人的临床状况。
由于既不肺功能也不胸部CT异常PAP血浆中的劣化特性,串行WLLs疗法重新提起。由于血浆置换完成后,三种WLL治疗方法已被要求(2006年3月,2006年7月和2007年5月)。虽然PAP的肺部表现仍然存在,WLL疗法已治疗血浆比以前它之后需要那么频繁。Interestingly, the serum GM-CSF autoantibody level has continued to decline from its value of 153 μg·mL-1在血浆置换完成时,取56°g·mL-1。
讨论
本文报道了在意大利帕维亚作者研究中心使用连续WLLs和血浆置换治疗一名巴氏患者,该患者与其他类似患者相比,对WLL反应不佳。血浆分离的基本原理是基于GM-CSF自身抗体在巴氏阴道炎中具有致病性的概念1,而血浆可以减少自身抗体水平足够通过在肺泡巨噬细胞的表面活性剂还原分解代谢改善表面活性剂的间隙3。而患者的初始血清GM-CSF自身抗体水平是相当高的,血浆去除明显降低了浓度,以类似的方式由邦菲尔德报告的结果等。3。然而,它不能降低水平到130磅·毫升-1,尽管连续10次血浆置换治疗超过2个月。这个结果的浓度高于平均值±SEMserum GM-CSF autoantibody level in 158 autoimmune PAP patients with active lung disease (113±7 μg·mL-1)1使用相同的ELISA法测定五。这也大大高于预测的危险阈值,发展自身免疫性PAP的肺部表现6。由于在高浓度的GM-CSF自身抗体的自身抗体实际水平确实与PAP肺疾病的严重程度相关成分的不6,这是不奇怪的血浆置换与临床改善相关,因为它并没有减少低于临界阈值水平。因此,本研究结果表明,在从血浆GM-CSF自身抗体水平小的减少预期不具有治疗效果。需要进一步研究以确定是否在自身抗体浓度更大的降低可以是治疗性;这可以与更积极的血浆方案历时7-14天理论上实现,在<3天的间隔,具有五个或更多的交流7。然而,风险/效益,必须仔细考虑的内在易感性增加的评估,以通过PAP患者感染显示1。
It is interesting that the serum GM-CSF autoantibody concentration continued to decline for 24 months after completion of plasmapheresis to less than half the value present at the end of these treatments. The reason for this is unclear. It is possible that the sequential WLLs removed a substance that stimulates the production of GM-CSF autoantibodies. Alternatively, WLL may remove significant numbers of the antibody-producing cells themselves, thereby reducing the circulating GM-CSF autoantibody levels. In either case, it is possible that the combination of a systemic treatment (plasmapheresis) and a local treatment (WLL) may act synergistically to lower the production of GM-CSF autoantibodies. While neither WLL nor plasmapheresis alone were sufficient to produce sustained benefit in this case, the combination of the two may have been beneficial.
还需要进一步的研究来确定降低粒细胞-巨噬细胞集落刺激因子自身抗体水平到低于肺泡蛋白沉积症发生的阈值的效用。
利益声明
没有宣布。
- 收到了2008年6月28日。
- 公认2008年10月2日。
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