Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Transl Med. 2010 Oct 14;8:97. doi: 10.1186/1479-5876-8-97.
Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS) and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction.
Using Luciferase Immunoprecipitation Systems (LIPS), a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time.
From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected.
The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.
在急性炎症期间，针对人体自身抗原诱导体液反应的情况知之甚少。我们利用一种高度敏感的抗体分析技术，研究了急性呼吸窘迫综合征（ARDS）和严重脓毒症患者的自身抗体，这两种疾病的特点是免疫激活剧烈，导致多器官功能障碍。
使用 Luciferase Immunoprecipitation Systems（LIPS），对一组对照、ARDS 和脓毒症患者的样本进行了针对一组自身抗原的抗体检测。将抗体滴度大于 24 个对照样本的平均值加 3 个标准差的样本用于识别血清阳性样本。然后对来自不同血清阳性 ARDS 和脓毒症患者的可用纵向样本进行分析，这些样本从入住重症监护病房的头两天开始，以分析随时间变化的自身抗体变化。
通过对患者血浆进行筛选，57%的 ARDS 患者和 46%无 ARDS 的脓毒症患者与对照组相比，至少有一种自身抗体的滴度显著升高。针对一系列自身抗原，包括钾通道调节剂、胃 ATP 酶、谷氨酸脱羧酶-65 和几种细胞因子，检测到频繁出现高滴度抗体。对系列样本的分析表明，一些血清阳性患者在早期时间点的自身抗体滴度较低，这些抗体通常会急剧上升，并在第 7-14 天达到峰值。此外，使用治疗剂量的皮质类固醇并不能降低自身抗体滴度的升高。在某些情况下，患者的自身抗体滴度在最后一次采集的血清样本中仍然升高。
ARDS 和严重脓毒症中自身抗体的快速诱导表明，持续的全身炎症和相关的组织破坏介导了对这些自身蛋白的耐受破坏。
