Serum and organ-associated anti-hemoglobin humoral autoreactivity: Association with anti-Sm responses and inflammation
Serum and organ-associated anti-hemoglobin humoral autoreactivity: Association with anti-Sm responses and inflammation
复制标题
DOI：
10.1002/eji.201040989
复制
发表时间：
2011-02-01
影响因子：
5.4
通讯作者：
Pal, Rahul
中科院分区：
文献类型：
--
作者：
Bhatnagar, Harshita;Kala, Smriti;Pal, Rahul
血红蛋白（Hb）的释放发生在一些以炎症为特征的感染性和自身免疫性疾病中。随着触珠蛋白（Hp）水平下降，游离血红蛋白可能会导致病理学。在系统性红斑狼疮（SLE）、利什曼原虫和疟疾患者的血清中证实了对人血红蛋白的体液自身反应性。狼疮易感小鼠的血清抗鼠Hb抗体水平也表现出年龄依赖性增加，进行性器官隔离;抗dsDNA抗体观察到显著的同型相关性。抗-Hb和抗-Sm反应之间的联系进行了观察：人狼疮血清表达抗-Sm抗体反应优先含有抗-Hb自身抗体的水平升高，免疫狼疮易感小鼠Sm导致增强抗鼠Hb反应。人和鼠抗Hb单克隆抗体的产生，其中一些是优先反应对疾病相关的高铁血红蛋白。表位作图研究揭示了分子内交叉反应的证据。一种这样的自身抗体与Hb协同作用以增强促炎细胞因子的分泌，同时引起来自内皮细胞的单核细胞迁移信号的产生增加。尽管记录了体细胞突变，但未观察到特异性可变区基因片段的优先使用。这些研究表明，虽然抗Hb自身反应性抗体的病因、特异性和序列可能不同，但它们发生得相当频繁，并可能产生炎症后果。
The release of hemoglobin (Hb) occurs in some infectious and autoimmune diseases characterized by inflammation. As levels of haptoglobin (Hp) fall, free Hb can cause pathology. Humoral autoreactivity to human Hb was demonstrated in the sera of systemic lupus erythematosus (SLE), leishmania and malaria patients. Serum anti-murine Hb antibody levels in lupus-prone mice also exhibited an age-dependent increase, with progressive organ sequestration; significant isotypic correlation was observed with anti-dsDNA antibodies. A suggestive link between anti-Hb and anti-Sm responses was observed: Human lupus sera expressing anti-Sm antibody reactivity preferentially contained heightened levels of anti-Hb autoantibodies, and immunization of lupus-prone mice with Sm led to enhanced anti-murine Hb reactivity. Human and murine anti-Hb monoclonal antibodies were generated, some of which were preferentially reactive toward disease-associated methemoglobin. Epitope-mapping studies revealed evidence of intramolecular cross-reactivity. One such autoantibody synergized with Hb to enhance the secretion of pro-inflammatory cytokines while eliciting the increased production of monocyte migratory signals from endothelial cells. Preferential usage of specific variable region gene segments was not observed, although somatic mutations were documented. These studies reveal that, while the etiology, specificity and sequences of anti-Hb auto-reactive antibodies can vary, they occur quite frequently and can have inflammatory consequences.