PNAS：类风湿性关节炎中耐药性的分子标记

2015-03-02 佚名生物谷

类风湿性关节炎是一种十分常见的自身免疫疾病，临床上的特征以及治疗反应的特异性受到包括遗传，环境以及免疫因素等多方面的影响。然而这些因素并不能很好地适用于治疗方式的预测。目前一线的治疗类风湿关节炎的药物是低剂量的氨甲喋呤（MTX）-一类叶酸代谢抑制剂，然而有相当一部分患者对此类药物的治疗效果并不明显，原因未知。由于除了抗叶酸代谢之外，MTX还能够促进腺嘌呤（ADO）在胞外的积累，而ADO的产生与Tr

类风湿性关节炎是一种十分常见的自身免疫疾病，临床上的特征以及治疗反应的特异性受到包括遗传，环境以及免疫因素等多方面的影响。然而这些因素并不能很好地适用于治疗方式的预测。目前一线的治疗类风湿关节炎的药物是低剂量的氨甲喋呤（MTX）-一类叶酸代谢抑制剂，然而有相当一部分患者对此类药物的治疗效果并不明显，原因未知。由于除了抗叶酸代谢之外，MTX还能够促进腺嘌呤（ADO）在胞外的积累，而ADO的产生与Treg表面的CD39/CD73具有密切的联系。巴西圣保罗大学药学系的Fernando Q. Cunha研究组针对此问题研究了Treg表面CD39与MTX的抗自身免疫病的关系，相关结果发表在最近一期的PNAs杂志上。

首先，作者随机收集了接受MTX药物治疗的122名RA患者样本，其中69位对MTX治疗效果不明显（UR-MTX），57位对MTX治疗效果明显（R-MTX）。另外还有33名健康人作为对照样本。通过细胞特征分析，作者发现R-MTX患者样本中Treg的数量与比例要明显高于另外两组，说明MTX的疗效与Treg具有一定的联系。进一步研究发现，R-MTX患者体内CD39+ Treg明显多于其它两组。而且通过定量分析Treg表面的CD39的表达量，作者发现UR-MTX患者Treg细胞表面的CD39表达水平要明显低于R-MTX患者以及健康人。同时CD73的相关分析呈阴性。

之后，作者分析了UR-MTX患者体内CD39的地表达量与ADO生成及释放之间的联系。作者将患者与健康人的Treg以及Tcon细胞分理出来进行体外培养，同时加入ADP进行共同孵育。一段时间后通过HPLC的方式检测上清中ADO的产生量。结果显示，相较于R-MTX以及健康人，UR-MTX患者Treg生产ADO的能力受到了很大程度的阻碍。而各组样本中Tcon细胞产生ADO的能力之间没有明显差异。另外，作者通过体外共培养Treg与Tcon的方式检测了Treg对于CD3/CD28刺激作用下Tcon增殖的抑制作用。结果显示，相对于R-MTX以及健康组，UR-MTX组的Treg抑制细胞增殖的能力明显偏弱。

之后，作者分析了CD39在Treg表面的低表达是UR-MTX患者本身的特征还是接受MTX刺激后产生的应激反应。首先，作者证明使用MTX进行治疗并不是造成MTX耐药性的原因。另外，在MTX刺激之前，UR-MTX患者与R-MTX患者体内Treg的数量与比例并没有明显差异，而在使用之后，R-MTX组的Treg较UR-MTX组发生明显的上升。同理，CD39+Treg的比例也具有相似特征。以上结果说明MTX的抗炎症机制与Treg的扩增具有因果关系。之后，作者通过比较MTX刺激前后不同组的Treg表面CD39的表达量，发现不论刺激与否，R-MTX组Treg表达量远高于UR-MTX组。以上结果说明Treg表面CD39的表达量是个体自身具有的一种特征，而且影响了MTX治疗RA的效果。

最后，作者通过小鼠关节炎模型证明了MTX是通过Treg以及CD39发挥作用的假说。

这一研究的意义在于：一方面揭示了MTX治疗RA的一种分子机制，并对不同患者对MTX的治疗效果差异做出了解释；另一方面对临床上进行RA治疗方案选择上增加了一种可供参考的分子标记，即CD39的表达水平。

原始出处

Peres RS1, Liew FY2, Talbot J1, Carregaro V3, Oliveira RD4, Almeida SL4, França RF1, Donate PB1, Pinto LG1, Ferreira FI5, Costa DL3, Demarque DP6, Gouvea DR6, Lopes NP6, Queiroz RH5, Silva JS3, Figueiredo F7, Alves-Filho JC1, Cunha TM1, Ferreira SH8, Louzada-Junior P9, Cunha FQ8.Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis.Proc Natl Acad Sci U S A. 2015 Feb 24;

版权声明：
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
在此留言

评论区 (5)

#插入话题

插入图片

[GetPortalCommentsPageByObjectIdResponse(id=19185, encodeId=10d619185bd, content=方面揭示了MTX治疗RA的一种分子机制，并对不同患者对MTX的治疗效果差异做出了解释；另一方面对临床上进行RA治疗方案选择上, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855703, encodeId=30871855e0367, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Sat May 23 00:17:00 CST 2015, time=2015-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1265241, encodeId=07331265241cd, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333773, encodeId=12301333e737b, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483379, encodeId=14e014833e9ba, content=<a href='/topic/show?id=55a6100826cc' target=_blank style='color:#2F92EE;'>#风湿性关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
2015-03-31 x35042875

方面揭示了MTX治疗RA的一种分子机制，并对不同患者对MTX的治疗效果差异做出了解释；另一方面对临床上进行RA治疗方案选择上

100 0
[GetPortalCommentsPageByObjectIdResponse(id=19185, encodeId=10d619185bd, content=方面揭示了MTX治疗RA的一种分子机制，并对不同患者对MTX的治疗效果差异做出了解释；另一方面对临床上进行RA治疗方案选择上, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855703, encodeId=30871855e0367, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Sat May 23 00:17:00 CST 2015, time=2015-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1265241, encodeId=07331265241cd, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333773, encodeId=12301333e737b, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483379, encodeId=14e014833e9ba, content=<a href='/topic/show?id=55a6100826cc' target=_blank style='color:#2F92EE;'>#风湿性关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
2015-05-23 drwjr

#PNAS#

27 0
[GetPortalCommentsPageByObjectIdResponse(id=19185, encodeId=10d619185bd, content=方面揭示了MTX治疗RA的一种分子机制，并对不同患者对MTX的治疗效果差异做出了解释；另一方面对临床上进行RA治疗方案选择上, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855703, encodeId=30871855e0367, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Sat May 23 00:17:00 CST 2015, time=2015-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1265241, encodeId=07331265241cd, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333773, encodeId=12301333e737b, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483379, encodeId=14e014833e9ba, content=<a href='/topic/show?id=55a6100826cc' target=_blank style='color:#2F92EE;'>#风湿性关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
2015-03-04 lmm397

#关节炎#

26 0
[GetPortalCommentsPageByObjectIdResponse(id=19185, encodeId=10d619185bd, content=方面揭示了MTX治疗RA的一种分子机制，并对不同患者对MTX的治疗效果差异做出了解释；另一方面对临床上进行RA治疗方案选择上, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855703, encodeId=30871855e0367, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Sat May 23 00:17:00 CST 2015, time=2015-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1265241, encodeId=07331265241cd, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333773, encodeId=12301333e737b, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483379, encodeId=14e014833e9ba, content=<a href='/topic/show?id=55a6100826cc' target=_blank style='color:#2F92EE;'>#风湿性关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
2015-03-04 ms4964546379600229

#类风湿#

22 0
[GetPortalCommentsPageByObjectIdResponse(id=19185, encodeId=10d619185bd, content=方面揭示了MTX治疗RA的一种分子机制，并对不同患者对MTX的治疗效果差异做出了解释；另一方面对临床上进行RA治疗方案选择上, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Tue Mar 31 23:21:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855703, encodeId=30871855e0367, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Sat May 23 00:17:00 CST 2015, time=2015-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1265241, encodeId=07331265241cd, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333773, encodeId=12301333e737b, content=<a href='/topic/show?id=5306e6164b6' target=_blank style='color:#2F92EE;'>#类风湿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76164, encryptionId=5306e6164b6, topicName=类风湿)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq2AGzrugK9ZUjU3eJxzM901ophWib0xJDrSicy49ibWl3zB5pbDto7eoR6tnzwOiaKdbq1a8PcbYFFrw/132, createdBy=6ff22500098, createdName=ms4964546379600229, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483379, encodeId=14e014833e9ba, content=<a href='/topic/show?id=55a6100826cc' target=_blank style='color:#2F92EE;'>#风湿性关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Wed Mar 04 00:17:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
2015-03-04 ms1467340776200723

#风湿性关节炎#

43 0

内科

外科

专科科室

热点

按科室浏览

临床工具

科研工具

其他工具

科研数智化

真实世界研究解决方案

数字化学术传播解决方案

其它

风湿免疫科

PNAS：类风湿性关节炎中耐药性的分子标记

相关资讯

科室

工具

服务