Laboratory of Clinical Infectious Diseases, Bethesda, MD, USA.
J Infect Dis. 2012 Sep 15;206(6):943-51. doi: 10.1093/infdis/jis431. Epub 2012 Jul 10.
Granulibacter bethesdensis is a recently described member of the Acetobacteraceae family that has been isolated from patients with chronic granulomatous disease (CGD). Its pathogenesis, environmental reservoir(s), and incidence of infection among CGD patients and the general population are unknown.
Detected antigens were identified by mass spectroscopy after 2-dimensional electrophoresis and immunoaffinity chromatography. The prevalence of Granulibacter immunoreactivity was assessed through immunoblotting and enzyme-linked immunosorbent assay (ELISA).
Methanol dehydrogenase (MDH) and formaldehyde-activating enzyme were recognized during analysis of sera from infected patients. Unique patterns of immunoreactive bands were identified in Granulibacter extracts, compared with extracts of other Acetobacteraceae species. By use of criteria based on these specific bands, specimens from 79 of 175 CGD patients (45.1%) and 23 of 93 healthy donors (24.7%) reacted to all 11 bands. An ELISA that used native MDH to capture and detect immunoglobulin G was developed and revealed high-titer MDH seroreactivity in culture-confirmed cases and 5 additional CGD patients. Testing of samples collected prior to culture-confirmed infection demonstrated instances of recent seroconversion, as well as sustained seropositivity. Infection of CGD mice with G. bethesdensis confirmed acquisition of high-titer antibody-recognizing MDH.
These serologic tests suggest that Granulibacter immunoreactivity is more common among CGD patients and, perhaps, among healthy donors than was previously suspected. This finding raises the possibility that clinical presentations of Granulibacter infection may be underappreciated.
Granulibacter bethesdensis 是最近在患有慢性肉芽肿病 (CGD) 的患者中分离出来的醋酸杆菌科的一个成员。其发病机制、环境储库以及 CGD 患者和一般人群中的感染发生率尚不清楚。
通过二维电泳和免疫亲和层析后，质谱分析鉴定了检测到的抗原。通过免疫印迹和酶联免疫吸附试验（ELISA）评估 Granulibacter 免疫反应性的流行率。
在感染患者的血清分析中发现了甲醇脱氢酶（MDH）和甲醛激活酶。与其他醋酸杆菌科的提取物相比，Granulibacter 提取物中鉴定出了独特的免疫反应性带模式。根据这些特异性带的标准，175 名 CGD 患者中的 79 名（45.1%）和 93 名健康供体中的 23 名（24.7%）的标本与所有 11 条带均发生反应。使用天然 MDH 捕获和检测免疫球蛋白 G 的 ELISA 被开发出来，并且在培养确认的病例和另外 5 名 CGD 患者中显示出高滴度的 MDH 血清反应性。在培养确认感染之前收集的样本测试表明存在近期血清转化的实例，以及持续的血清阳性。用 G. bethesdensis 感染 CGD 小鼠证实了获得高滴度抗体识别 MDH。
这些血清学检测表明，Granulibacter 免疫反应性在 CGD 患者中比以前怀疑的更为常见，也许在健康供体中也是如此。这一发现增加了 Granulibacter 感染临床表现可能被低估的可能性。
