Grossmayer Gerhard E, Munoz Luis E, Gaipl Udo S, Franz Sandra, Sheriff Ahmed, Voll Reinhard E, Kalden Joachim R, Herrmann Martin
Institute for Clinical Immunology, Department of Medicine 3, Friedrich-Alexander University of Erlangen-Nuremberg, Glückstrasse 4a, 91054, Erlangen, Germany.
Mod Rheumatol. 2005;15(6):383-90. doi: 10.1007/s10165-005-0430-x.
Systemic lupus erythematosus (SLE) is a very heterogeneous systemic autoimmune disease, in which autoantibody synthesis against nuclear constituents is the main immunological characteristic. These autoantibodies underwent affinity maturation and isotype switching. Additionally, T-cell tolerance against nuclear autoantigens should be affected in these autoimmune patients. Nuclear material derived from apoptotic and/or necrotic cells may serve as an important source of autoantigens. However, dead and dying cells as well as cellular debris are rapidly removed from tissues by phagocytes without eliciting inflammation or immune responses under healthy conditions. During apoptosis nuclear components are strongly modified through enzymatic reactions. If these cells are not timely cleared, those autoantigens may be released, taken up, and presented by dendritic cells in tissues or presented by follicular dendritic cells in lymph nodes to T and B cells, respectively. This could be a mechanism for breaking the peripheral self-tolerance. In this article we focus on the deficient clearance of apoptotic cells in SLE patients and its importance in development of this autoimmune disease.
系统性红斑狼疮（SLE）是一种高度异质性的全身性自身免疫性疾病，其中针对核成分的自身抗体合成是主要的免疫学特征。这些自身抗体经历了亲和力成熟和同种型转换。此外，这些自身免疫患者对核自身抗原的T细胞耐受性应该受到影响。源自凋亡和/或坏死细胞的核物质可能是自身抗原的重要来源。然而，在健康条件下，死亡和濒死细胞以及细胞碎片会被吞噬细胞迅速从组织中清除，而不会引发炎症或免疫反应。在细胞凋亡过程中，核成分会通过酶促反应发生强烈修饰。如果这些细胞没有被及时清除，那些自身抗原可能会被释放，被组织中的树突状细胞摄取并呈递，或者分别被淋巴结中的滤泡树突状细胞呈递给T细胞和B细胞。这可能是打破外周自身耐受性的一种机制。在本文中，我们重点关注SLE患者凋亡细胞的清除缺陷及其在这种自身免疫性疾病发展中的重要性。
