Rituximab treatment in a patient with severe thyroid-associated ophthalmopathy: Effects on orbital lymphocytic infiltrates
Rituximab treatment in a patient with severe thyroid-associated ophthalmopathy: Effects on orbital lymphocytic infiltrates
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DOI：
10.1016/j.clim.2008.12.005
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发表时间：
2009-05-01
影响因子：
8.6
通讯作者：
Beck-Peccoz, Paolo
中科院分区：
文献类型：
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作者：
Salvi, Mario;Vannucchia, Guia;Beck-Peccoz, Paolo
利妥昔单抗（RTX）已被证明在以前的工作，以改善甲状腺相关眼病（TAO），但非常少的数据是在靶组织中的RTX的影响。我们研究了RTX对一名严重TAO患者外周淋巴细胞和眶内浸润的影响，该患者接受了两个周期的治疗。3例中重度TAO患者和1例重度TAO患者减压时取眶内组织作为对照，采用标准免疫抑制剂治疗。在整个研究期间分析外周血淋巴细胞，减压时分析白色眶内组织淋巴细胞。在接受RTX治疗的患者中，尽管存在一定比例的持续CD 19+细胞，但对外周CD 20+细胞耗竭的反应是视野和视力改善。RTX再治疗后，患者的视神经功能仅短暂改善。眼眶组织中CD 20+细胞数（0-1%）低于外周血（3%）。与外周相比，在眼眶中观察到更大百分比的CD 19+，其中大部分为CD 19+5+（80%）。通过免疫组化，所有对照患者的眼眶组织均显示CD 20+和CD 3+细胞，与TAO的持续时间以及类固醇或放疗治疗无关。这是第一份关于RTX治疗与眶内CD 20+淋巴细胞耗竭相关的活动性重度TAO的疗效报告。RTX后，CD 19+5+淋巴细胞在眼眶浸润中比CD 20+细胞多2-3倍。自身反应性细胞的持续存在被认为与TAO复发有关。(C)2009 Elsevier Inc. All rights reserved.
Rituximab (RTX) has been shown in previous work to improve thyroid-associated ophthatmopathy (TAO), but very little data is available on the effects of RTX in the target tissues. We studied the effects of RTX on peripheral lymphocytes and on the intra-orbital infiltrates in one patient with severe TAO who was treated with two cycles of therapy. Intra-orbital tissues derived at decompression from 3 patients with moderate-severe and 1 with severe TAO, treated with standard immunosuppression, were studied as controls. Peripheral blood lymphocytes were analyzed throughout the study period, white intra-orbital tissue lymphocytes at decompression. In the patient treated with RTX visual field and acuity improved in response to peripheral CD 20+ cell depletion, although there was a proportion of persisting CD 19+ cells. After RTX re-treatment the patient's optic nerve function improved only transiently. The number of CD 20+ cells was lower in orbital tissues (0-1%) than in the peripheral blood (3%). A greater percentage of CD 19+ was observed in the orbits compared to the periphery, most of which were CD 19+5+ (80%). By immunohistochemistry, orbital tissues from all control patients showed CD 20+ and CD 3+ cells, independently of the duration of TAO and of the treatment with either steroids or radiotherapy. This is the first report on the therapeutic effect of RTX in active, severe TAO associated to the depletion of intra-orbital CD 20+ lymphocytes. After RTX, CD 19+5+ lymphocytes were shown to be 2-3 times more prevalent in the orbital infiltrates, compared to CD 20+ cells. Persistence of autoreactive cells is believed to be related to TAO relapse. (C) 2009 Elsevier Inc. All rights reserved.