A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.
A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.
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作者：
自身免疫性疾病很常见，而且会使人虚弱，但如果有生物标记物允许个性化定制控制这些疾病所需的潜在毒性免疫抑制疗法，那么它们的严重表现就可以减少。基于基因表达的生物标记物有助于癌症患者个体化化疗，但不利于自身免疫，已被识别并转化为临床实践。我们发现，纯化的CD8 T细胞的转录图谱避免了未分离细胞的混淆影响，识别了两个不同的患者亚组，预测两种不同自身免疫性疾病的长期预后：抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV)，一种以中小型血管炎症为特征的慢性、严重疾病，以及系统性红斑狼疮(SLE)，其特征是自身抗体、免疫复合体沉积和从肾小球肾炎到神经功能障碍的各种临床表现。我们发现，定义预后不良组的基因富含IL7R途径、TCR信号和记忆T细胞表达的基因。此外，预后不良的组与CD8 T细胞记忆群的扩大有关。这些亚群也在正常人群中发现，仅通过测量三个基因的表达就可以识别，它们增加了个体化治疗的前景，并提出了自身免疫的新的潜在治疗靶点。
Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of the potentially toxic immunosuppressive therapy required for their control. Gene expression-based biomarkers facilitating individual tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8 T cells, which avoids the confounding influences of unseparated cells, identifies two distinct patient subgroups predicting long-term prognosis in two different autoimmune diseases, anti-neutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that genes defining the poor prognostic group are enriched for genes of the IL7R pathway, TCR signalling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8 T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest novel potential therapeutic targets in autoimmunity.
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影响因子：
13.6
作者：
Jennette, JC;Xiao, H;Falk, RJ
通讯作者：
Falk, RJ
影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
DOI：
10.1073/pnas.2336198100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Pellegrini, M;Belz, G;Strasser, A
通讯作者：
Strasser, A
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
64.8
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
通讯作者：
Lanzavecchia, A