Lymphocytic vasculitis in X-linked lymphoproliferative disease
Lymphocytic vasculitis in X-linked lymphoproliferative disease
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DOI：
10.1182/blood.v97.1.95
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发表时间：
2001-01-01
期刊：
影响因子：
20.3
通讯作者：
Tan, RS
中科院分区：
文献类型：
--
作者：
Dutz, JP;Benoit, L;Tan, RS
系统性血管炎是X连锁淋巴组织增生性疾病（XLP）的一种罕见表现，XLP是一种对EB病毒（EBV）存在选择性免疫缺陷的疾病。作者描述了一名因慢性系统性血管炎而死亡的患者，该患者符合XLP诊断的临床标准。对该患者SAP基因的测序发现了一个影响SH2结构域的新点突变。患者表现为病毒相关性噬血细胞综合征（VAHS），随后出现脉络膜视网膜炎、支气管扩张和低丙种球蛋白血症。他进一步发展为单神经炎和致命的呼吸衰竭。尸检时发现广泛的中小血管炎证据，累及视网膜、脑和冠状动脉以及肾脏、睾丸和胰腺的节段性血管。使用CD20、CD45RO和CD8抗体的免疫组织化学分析显示，血管壁浸润主要由CD8（+）T细胞组成，这意味着对抗原的细胞毒性T淋巴细胞反应。用聚合酶链反应（PCR）技术在浸润血管的动脉壁组织中检测到EBV DNA，进一步表明CD8（+）T细胞靶向内皮细胞内的EBV抗原。作者提出SAP蛋白功能失活可损害对EBV的免疫应答，导致系统性血管炎。(C)2001年，美国血液学会。
Systemic vasculitis is an uncommon manifestation of X-linked lymphoproliferative die ease (XLP), a disorder in which there is a selective immune deficiency to Epstein-Barr virus (EBV), The molecular basis for XLP has recently been ascribed to mutations within SLAM-associated protein (SAP), an SH2 domain-containing protein expressed primarily in T cells. The authors describe a patient who died as a result of chronic systemic vasculitis and fulfilled clinical criteria for the diagnosis of XLP. Sequencing of this patient's SAP gene uncovered a novel point mutation affecting the SH2 domain. The patient presented with virus-associated hemophagocytic syndrome (VAHS) and later had chorioretinitis, bronchiectasis, and hypogammaglobulinemia develop. He further developed mononeuritis and fatal respiratory failure. Evidence of widespread small and medium vessel vasculitis was noted at autopsy with involvement of retinal, cerebral, and coronary arteries as well as the segmental vessels of the kidneys, testes, and pancreas. Immunohistochemical analysis using antibodies to CD20, CD45RO, and CD8 revealed that the vessel wall infiltrates consisted primarily of CD8(+) T cells, implying a cytotoxic T-lymphocyte response to antigen. EBV DNA was detected by polymerase chain reaction (PCR) in arterial wall tissue microdissected from infiltrated vessels further suggesting that the CD8(+) T cells were targeting EBV antigens within the endothelium, The authors pre pose that functional inactivation of the SAP protein can impair the immunologic response to EBV, resulting in systemic vasculitis. (C) 2001 by The American Society of Hematology.