Grom Alexei A
Cincinnati Children's Hospital Medical Center, OH 45215, USA.
Curr Opin Rheumatol. 2003 Sep;15(5):587-90. doi: 10.1097/00002281-200309000-00011.
One of the most perplexing features of systemic-onset juvenile rheumatoid arthritis is the association with macrophage activation syndrome, a life-threatening complication caused by excessive activation and proliferation of T cells and macrophages. The main purpose of the review is to summarize current understanding of the relation between macrophage activation syndrome and other clinically similar hemophagocytic disorders.
Clinically, macrophage activation syndrome has strong similarities with familial and virus-associated reactive hemophagocytic lymphohistiocytosis. The better understood familial hemophagocytic lymphohistiocytosis is a constellation of rare, autosomal recessive immune disorders. The most consistent immunologic abnormalities in patients with familial hemophagocytic lymphohistiocytosis are decreased natural killer and cytotoxic cell functions. In approximately one third of familial hemophagocytic lymphohistiocytosis patients, these immunologic abnormalities are secondary to mutations in the gene encoding perforin, a protein that mediates cytotoxic activity of natural killer and cytotoxic CD8+ T cells. Several recent studies have suggested that profoundly depressed natural killer cell activity and abnormal levels of perforin expression may be a feature of macrophage activation syndrome in systemic-onset juvenile rheumatoid arthritis as well. Although it has been proposed that in both hemophagocytic lymphohistiocytosis and macrophage activation syndrome, natural killer and cytotoxic cell dysfunction may lead to inadequate control of cellular immune responses, the exact nature of such dysregulation and the relation between macrophage activation syndrome and hemophagocytic lymphohistiocytosis still remain to be determined.
全身型幼年特发性关节炎最令人困惑的特征之一是与巨噬细胞活化综合征相关，这是一种由T细胞和巨噬细胞过度活化和增殖引起的危及生命的并发症。本综述的主要目的是总结目前对巨噬细胞活化综合征与其他临床相似的噬血细胞性疾病之间关系的认识。
在临床上，巨噬细胞活化综合征与家族性及病毒相关的反应性噬血细胞性淋巴组织细胞增生症有很强的相似性。人们对家族性噬血细胞性淋巴组织细胞增生症有了更好的了解，它是一组罕见的常染色体隐性免疫疾病。家族性噬血细胞性淋巴组织细胞增生症患者最一致的免疫异常是自然杀伤细胞和细胞毒性细胞功能下降。在大约三分之一的家族性噬血细胞性淋巴组织细胞增生症患者中，这些免疫异常继发于编码穿孔素的基因突变，穿孔素是一种介导自然杀伤细胞和细胞毒性CD8+T细胞细胞毒性活性的蛋白质。最近的几项研究表明，自然杀伤细胞活性严重降低和穿孔素表达水平异常也可能是全身型幼年特发性关节炎中巨噬细胞活化综合征的一个特征。尽管有人提出，在噬血细胞性淋巴组织细胞增生症和巨噬细胞活化综合征中，自然杀伤细胞和细胞毒性细胞功能障碍可能导致细胞免疫反应控制不足，但这种失调的确切性质以及巨噬细胞活化综合征与噬血细胞性淋巴组织细胞增生症之间的关系仍有待确定。
