Frontiers in Immunology: IL-40:一种新的B细胞相关细胞因子在利妥昔单抗治疗类风湿性关节炎后上调减少,并与疾病活性、自身抗体和NETosis相关

2021-11-08 彼岸河边草 MedSci原创

白细胞介素40 (IL-40)是一种新发现的B细胞相关细胞因子,该研究主要探究IL-40在类风湿性关节炎(RA)中的功能。

     背景:白细胞介素40 (IL-40)是一种新发现的B细胞相关细胞因子,与体液免疫反应和B细胞稳态有关。由于B细胞在自身免疫中起关键作用,该研究主要探究IL-40在类风湿性关节炎(RA)中的功能。

      方法:在RA和骨关节炎(OA)患者的滑膜组织中测定了IL-40表达。此外,在RAn=50)、系统性红斑狼疮(SLEn=69)、OA患者(n=44)和健康对照(HCn=50)的血清/滑液中测量了IL-40。研究者评估了利妥昔单抗清除B细胞后(n=29) 或阿达木单抗抑制TNF (n=25) RA患者IL-40水平的变化。检查了IL-40、疾病活动性、自身抗体、细胞因子和NETosis标志物之间的关系。探究了IL-40对滑膜成纤维细胞的影响。

     结果:IL-40在RA滑膜组织中过度表达,特别是滑膜衬里和浸润免疫细胞。与OA 患者相比,RA患者的滑液中IL-40水平上调(p<0.0001)。类似地,与HCOASLE 相比,RA患者血清中的IL-40增加(所有p<0.0001),并在利妥昔单抗治疗1624 周后降低(均p<0.01)。未观察到阿达木单抗对IL-40有显著影响。RA患者的IL-40水平与血清和滑膜液中的风湿因子-IgM抗环瓜氨酸肽​​anti-CCP)相关(均为p<0.0001 p<0.01)。滑液IL-40还与疾病活动性评分DAS28 (p<0.05)、滑液白细胞计数(p<0.01)、中性粒细胞引诱剂IL-8 (p<0.01)MIP-1α(p<0.01) 和中性粒细胞胞外陷阱(NETosis)的标志物,例如蛋白酶3 (p<0.0001)和中性粒细胞弹性蛋白酶(p<0.0001)相关联。与未受刺激的细胞相比,暴露于IL-40的滑膜成纤维细胞增加了IL-8 (p<0.01)MCP-1 (p<0.05) MMP-13 (p<0.01)的分泌。

      结论:该研究显示了RA中IL-40上调及其在B细胞耗竭治疗后的降低。IL-40与自身抗体、趋化因子和NETosis标志物关联可能暗示其参与RA发展。此外,IL-40上调滑膜成纤维细胞中趋化因子和 MMP-13的分泌,表明其在调节RA炎症和组织破坏中的作用。

出处:

Navra´ tilova´ A, Andre´ s Cerezo L, et al (2021) IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis. Front. Immunol. 12:745523.doi: 10.3389/fimmu.2021.745523

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    2022-09-15 anminleiryan
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topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581030, encodeId=a51c15810304e, content=<a href='/topic/show?id=99e9126e34f' target=_blank style='color:#2F92EE;'>#NETosis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12673, encryptionId=99e9126e34f, topicName=NETosis)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bdac16698014, createdName=ms8543593053280928, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1878432, encodeId=811018e843277, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Thu Sep 15 01:22:52 CST 2022, time=2022-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734433, encodeId=55f31e34433cf, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Wed Sep 14 08:22:52 CST 2022, time=2022-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660516, encodeId=2b9d166051625, content=<a href='/topic/show?id=c0de32285a1' target=_blank style='color:#2F92EE;'>#利妥昔#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32285, encryptionId=c0de32285a1, topicName=利妥昔)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a58d25117340, createdName=花花1374, createdTime=Sun Sep 04 22:22:52 CST 2022, time=2022-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809653, encodeId=111c180965386, content=<a href='/topic/show?id=6cd683e603b' target=_blank style='color:#2F92EE;'>#胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83760, encryptionId=6cd683e603b, topicName=胞因子)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/017ED6AFEB45F49165298113DDC0656A/100, createdBy=84182500174, createdName=ms7019579240139182, createdTime=Sat Sep 03 00:22:52 CST 2022, time=2022-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266345, encodeId=9159126634507, 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=0, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273418, encodeId=261312e341833, content=<a href='/topic/show?id=310d383ef5' target=_blank 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GetPortalCommentsPageByObjectIdResponse(id=1334316, encodeId=69a4133431683, 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=20, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483727, encodeId=dc121483e2783, 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=35, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581030, encodeId=a51c15810304e, content=<a href='/topic/show?id=99e9126e34f' target=_blank style='color:#2F92EE;'>#NETosis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12673, encryptionId=99e9126e34f, topicName=NETosis)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bdac16698014, createdName=ms8543593053280928, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1878432, encodeId=811018e843277, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Thu Sep 15 01:22:52 CST 2022, time=2022-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734433, encodeId=55f31e34433cf, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Wed Sep 14 08:22:52 CST 2022, time=2022-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660516, encodeId=2b9d166051625, content=<a href='/topic/show?id=c0de32285a1' target=_blank style='color:#2F92EE;'>#利妥昔#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32285, encryptionId=c0de32285a1, topicName=利妥昔)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a58d25117340, createdName=花花1374, createdTime=Sun Sep 04 22:22:52 CST 2022, time=2022-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809653, encodeId=111c180965386, content=<a href='/topic/show?id=6cd683e603b' target=_blank style='color:#2F92EE;'>#胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83760, encryptionId=6cd683e603b, topicName=胞因子)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/017ED6AFEB45F49165298113DDC0656A/100, createdBy=84182500174, createdName=ms7019579240139182, createdTime=Sat Sep 03 00:22:52 CST 2022, time=2022-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266345, encodeId=9159126634507, 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=0, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273418, encodeId=261312e341833, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1283687, encodeId=4118128368e92, content=<a href='/topic/show?id=2c00e784416' target=_blank style='color:#2F92EE;'>#细胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77844, encryptionId=2c00e784416, topicName=细胞因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0ad8182, createdName=axin009, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1334316, encodeId=69a4133431683, 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=20, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483727, encodeId=dc121483e2783, 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=35, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581030, encodeId=a51c15810304e, content=<a href='/topic/show?id=99e9126e34f' target=_blank style='color:#2F92EE;'>#NETosis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12673, encryptionId=99e9126e34f, topicName=NETosis)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bdac16698014, createdName=ms8543593053280928, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
    2021-11-11 lmm397
  6. 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style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1283687, encodeId=4118128368e92, content=<a href='/topic/show?id=2c00e784416' target=_blank style='color:#2F92EE;'>#细胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77844, encryptionId=2c00e784416, topicName=细胞因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0ad8182, createdName=axin009, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1334316, encodeId=69a4133431683, 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=20, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1483727, encodeId=dc121483e2783, 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=35, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581030, encodeId=a51c15810304e, content=<a href='/topic/show?id=99e9126e34f' target=_blank style='color:#2F92EE;'>#NETosis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12673, encryptionId=99e9126e34f, topicName=NETosis)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bdac16698014, createdName=ms8543593053280928, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
  7. 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encryptionId=6cd683e603b, topicName=胞因子)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/017ED6AFEB45F49165298113DDC0656A/100, createdBy=84182500174, createdName=ms7019579240139182, createdTime=Sat Sep 03 00:22:52 CST 2022, time=2022-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266345, encodeId=9159126634507, 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=0, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273418, encodeId=261312e341833, content=<a href='/topic/show?id=310d383ef5' target=_blank 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  8. 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encryptionId=6cd683e603b, topicName=胞因子)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/017ED6AFEB45F49165298113DDC0656A/100, createdBy=84182500174, createdName=ms7019579240139182, createdTime=Sat Sep 03 00:22:52 CST 2022, time=2022-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266345, encodeId=9159126634507, 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=0, 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=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273418, encodeId=261312e341833, content=<a href='/topic/show?id=310d383ef5' target=_blank 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topicList=[TopicDto(id=100826, encryptionId=55a6100826cc, topicName=风湿性关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c237911872, createdName=ms1467340776200723, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581030, encodeId=a51c15810304e, content=<a href='/topic/show?id=99e9126e34f' target=_blank style='color:#2F92EE;'>#NETosis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12673, encryptionId=99e9126e34f, topicName=NETosis)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bdac16698014, createdName=ms8543593053280928, createdTime=Thu Nov 11 01:22:52 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
  9. 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  10. 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