The CD4+ Lymphopenic Sarcoidosis Phenotype Is Highly Responsive to Anti-Tumor Necrosis Factor-α Therapy
The CD4+ Lymphopenic Sarcoidosis Phenotype Is Highly Responsive to Anti-Tumor Necrosis Factor-α Therapy
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DOI：
10.1378/chest.09-2576
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发表时间：
2010-06-01
期刊：
影响因子：
9.6
通讯作者：
Julian, Mark W.
中科院分区：
文献类型：
--
作者：
Crouser, Elliott D.;Lozanski, Gerard;Julian, Mark W.
目前结节病患者的治疗选择有限，并且不清楚哪种治疗对任何给定患者最有效。我们已经确定了一种结节病的表型，其特征是CD 4（+）淋巴细胞减少症和对常规免疫抑制剂（如皮质类固醇和甲氨蝶呤）的耐药性。基于最近的报道，肿瘤坏死因子（TNF）-α与调节性T细胞（Treg）功能障碍有关，我们假设结节病相关的CD 4（+）淋巴细胞减少症可以通过抗TNF-α治疗解决。连续5例CD 4（+）淋巴细胞减少症患者接受嵌合抗TNF α抗体（英夫利西单抗）治疗。在英夫利西单抗治疗前后评估临床疾病表现和外周血T细胞亚群。所有患者的外周血淋巴细胞和CD 4 + T细胞绝对计数均显著增加，并证实英夫利西单抗治疗后临床疾病表现有所改善。未观察到T细胞亚群分布的变化。CD 4（+）淋巴细胞减少症的存在表明了一种独特的结节病表型，对抗TNF α治疗特别敏感。胸部2010; 137（6）：1432-1435
The treatment options for patients with sarcoidosis are presently limited, and it is unclear which treatments are most effective for any given patient. We have identified a sarcoidosis phenotype characterized by CD4(+) lymphopenia and resistance to conventional immunosuppressants, such as corticosteroids and methotrexate. Based on recent reports linking tumor necrosis factor (TNF)-alpha to regulatory T-cell (Treg) dysfunction, we hypothesized that sarcoidosis-associated CD4(+) lymphopenia would resolve with anti-TNF alpha treatment. Five consecutive patients with CD4(+) lymphopenia were treated with a chimeric anti-TNF alpha antibody (infliximab). Clinical disease manifestations and peripheral blood T-cell subsets were assessed before and after infliximab treatment. All patients experienced significant increases in absolute peripheral blood lymphocyte and CD4(+) T-cell counts and demonstrated improvement in clinical disease manifestations in response to infliximab. No change in the distribution of T-cell subsets was noted. The presence of CD4(+) lymphopenia identifies a distinct sarcoidosis phenotype that is particularly responsive to anti-TNF alpha therapy. CHEST 2010; 137(6):1432-1435