Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to rituximab treatment.
Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to rituximab treatment.
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DOI：
10.1093/rheumatology/keq159
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Bokarewa MI
中科院分区：
文献类型：
--
作者：
Magnusson M;Brisslert M;Zendjanchi K;Lindh M;Bokarewa MI
目标.病毒可能导致RA。这促使我们监测RA患者的病毒载量和对抗CD 20治疗的反应。方法.在利妥昔单抗（RTX）治疗前和治疗后3个月，使用实时PCR分析了35例RA患者的血液和骨髓中的CMV、EBV、HSV-1、HSV-2、细小病毒B19和多瘤病毒，并与自身抗体和B细胞耗竭水平相关。对RTX的临床反应定义为6个月时28关节疾病活动评分（DAS-28）降低>1.3。结果RTX治疗前，35例患者中有15例（EBV阳性组）检出EBV，其中4例表达细小病毒。在8例患者（细小病毒阳性组）中进一步检测到细小病毒。12名患者对分析的病毒呈阴性。RTX后，EBV被清除，而细小病毒不受影响。18例患者为应答者，其中12例为EBV阳性。与细小病毒阳性组（P = 0.002）和病毒阴性组（P = 0.04）相比，EBV阳性组DAS-28的降低显著更高。大多数对RTX有反应的EBV阴性患者（75%）在接下来的11个月内需要重新治疗，而只有8%的EBV阳性患者需要重新治疗。RTX后观察到RF、Ig产生细胞和CD 19 + B细胞减少，但未区分病毒感染。然而，与EBV阴性组相比，EBV感染患者基线时Fas表达B细胞水平显著较高。结论. EB病毒和细小病毒基因组经常在RA患者的骨髓中发现。EB病毒基因组的存在与RTX的更好的临床反应相关。因此，EBV基因组的存在可以预测对RTX的临床反应。
Objectives. Viruses may contribute to RA. This prompted us to monitor viral load and response to anti-CD20 therapy in RA patients. Methods. Blood and bone marrow from 35 RA patients were analysed for CMV, EBV, HSV-1, HSV-2, parvovirus B19 and polyomavirus using real-time PCR before and 3 months after rituximab (RTX) treatment and related to the levels of autoantibodies and B-cell depletion. Clinical response to RTX was defined as decrease in the 28-joint disease activity score (DAS-28) >1.3 at 6 months. Results. Before RTX treatment, EBV was identified in 15 out of 35 patients (EBV-positive group), of which 4 expressed parvovirus. Parvovirus was further detected in eight patients (parvo-positive group). Twelve patients were negative for the analysed viruses. Following RTX, EBV was cleared, whereas parvovirus was unaffected. Eighteen patients were responders, of which 12 were EBV positive. The decrease in the DAS-28 was significantly higher in EBV-positive group compared with parvo-positive group (P = 0.002) and virus-negative patients (P = 0.04). Most of EBV-negative patients that responded to RTX (75%) required retreatment within the following 11 months compared with only 8% of responding EBV-positive patients. A decrease of RF, Ig-producing cells and CD19+ B cells was observed following RTX but did not distinguish between viral infections. However, EBV-infected patients had significantly higher levels of Fas-expressing B cells at baseline as compared with EBV-negative groups. Conclusions. EBV and parvovirus genomes are frequently found in bone marrow of RA patients. The presence of EBV genome was associated with a better clinical response to RTX. Thus, presence of EBV genome may predict clinical response to RTX.
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影响因子：
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作者：
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