Rapid induction of autoantibodies during ARDS and septic shock.
Rapid induction of autoantibodies during ARDS and septic shock.
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DOI：
10.1186/1479-5876-8-97
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发表时间：
2010-10-14
影响因子：
7.4
通讯作者：
Suffredini AF
中科院分区：
文献类型：
--
作者：
Burbelo PD;Seam N;Groot S;Ching KH;Han BL;Meduri GU;Iadarola MJ;Suffredini AF
在急性炎症过程中，针对人类自身抗原的体液应答的诱导知之甚少。我们利用高度敏感的抗体谱分析技术研究急性呼吸窘迫综合征（ARDS）和严重脓毒症患者的自身抗体，这些疾病的特征是强烈的免疫激活导致多器官功能障碍。使用荧光素酶免疫沉淀系统（LIPS），对对照组、ARDS和脓毒症患者进行了针对一组自身抗原的抗体检测。使用大于24份对照样本的平均值加3 SD的自身抗体滴度来鉴定血清阳性样本。从进入重症监护后的前两天内开始，分析来自不同血清阳性ARDS和脓毒症患者样本的可用纵向样本随时间的自身抗体变化。从筛选患者血浆中，与对照组相比，57%的ARDS和46%的无ARDS的脓毒症患者表现出至少一种统计学显著升高的自身抗体。经常检测到针对自身抗原谱的高滴度抗体，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。对系列样本的分析显示，几名血清阳性患者在早期时间点的自身抗体较低，这些抗体通常急剧上升，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没有减少自身抗体滴度的上升。在某些情况下，患者自身抗体滴度在采集的最后一份血清样品中保持升高。在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性的破坏。
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.
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影响因子：
16.2
作者：
Burbelo PD;Hirai H;Issa AT;Kingman A;Lernmark A;Ivarsson SA;Notkins AL;Iadarola MJ
通讯作者：
Iadarola MJ
DOI：
10.1084/jem.20091669
发表时间：
2010-02-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kisand K;Bøe Wolff AS;Podkrajsek KT;Tserel L;Link M;Kisand KV;Ersvaer E;Perheentupa J;Erichsen MM;Bratanic N;Meloni A;Cetani F;Perniola R;Ergun-Longmire B;Maclaren N;Krohn KJ;Pura M;Schalke B;Ströbel P;Leite MI;Battelino T;Husebye ES;Peterson P;Willcox N;Meager A
通讯作者：
Meager A
影响因子：
6.4
作者：
Gogos, CA;Drosou, E;Skoutelis, A
通讯作者：
Skoutelis, A
影响因子：
4.4
作者：
Puel, Anne;Picard, Capucine;Casanova, Jean-Laurent
通讯作者：
Casanova, Jean-Laurent
影响因子：
4.4
作者：
Hotchkiss, RS;Tinsley, KW;Karl, IE
通讯作者：
Karl, IE