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与伯氏考克斯体相关的 B 细胞非霍奇金淋巴瘤。

B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.

机构信息

Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Faculté de Médecine, Unité Mixte (UM) 63, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7278, Institut de Recherche Pour le Développement (IRD) 198, INSERM, U1095, Marseille, France;

Service de Médecine Interne, Nouvel Hôpital Civil, Strasbourg, France;

出版信息

Blood. 2016 Jan 7;127(1):113-21. doi: 10.1182/blood-2015-04-639617. Epub 2015 Oct 13.

Abstract

Bacteria can induce human lymphomas, whereas lymphoproliferative disorders have been described in patients with Q fever. We observed a lymphoma in a patient with Q fever that prompted us to investigate the association between the 2 diseases. We screened 1468 consecutive patients of the 2004 to 2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIRs) of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were calculated comparatively to the 2012 Francim Registry. The presence of Coxiella burnetii was tested using immunofluorescence and fluorescence in situ hybridization using a specific 16S ribosomal RNA probe and genomic DNA probe. Seven patients (0.48%) presented mature B-cell lymphoma consisting of 6 DLBCL and 1 FL. An excess risk of DLBCL and FL was found in Q fever patients compared with the general population (SIR [95% confidence interval], 25.4 [11.4-56.4] and 6.7 [0.9-47.9], respectively). C burnetii was detected in CD68(+) macrophages within both lymphoma and lymphadenitis tissues but localization in CD123(+) plasmacytoid dendritic cells (pDCs) was found only in lymphoma tissues. Q fever patients with persistent focalized infection were found more at risk of lymphoma (hazard ratio, 9.35 [1.10-79.4]). Interleukin-10 (IL10) overproduction (P = .0003) was found in patients developing lymphoma. These results suggest that C burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma, possibly by the infection of pDCs and IL10 overproduction. Screening for early lymphoma diagnosis should be considered in the management of patients with Q fever, especially those with persistent focalized infections.

摘要

细菌可诱发人类淋巴瘤,而 Q 热患者已被描述发生淋巴增生性疾病。我们观察到 1 例 Q 热患者发生淋巴瘤,促使我们调查这 2 种疾病之间的关联。我们筛选了 2004 年至 2014 年期间法国国家 Q 热参考中心数据库中 1468 例连续患者。使用免疫荧光法和使用特异性 16S 核糖体 RNA 探针和基因组 DNA 探针的荧光原位杂交法检测 Coxiella burnetii 的存在。使用免疫荧光法和荧光原位杂交法检测 Coxiella burnetii 的存在,使用特异性 16S 核糖体 RNA 探针和基因组 DNA 探针。7 例(0.48%)患者存在成熟 B 细胞淋巴瘤,包括 6 例弥漫性大 B 细胞淋巴瘤(DLBCL)和 1 例滤泡性淋巴瘤(FL)。与普通人群相比,Q 热患者中 DLBCL 和 FL 的风险增加(SIR [95%置信区间],25.4 [11.4-56.4]和 6.7 [0.9-47.9])。在淋巴瘤和淋巴结炎组织中的 CD68(+)巨噬细胞中检测到 C burnetii,但仅在淋巴瘤组织中发现 CD123(+)浆细胞样树突状细胞(pDC)中的定位。持续性局灶性感染的 Q 热患者发生淋巴瘤的风险更高(危险比,9.35 [1.10-79.4])。发现发生淋巴瘤的患者白细胞介素 10(IL10)过度产生(P =.0003)。这些结果表明,C burnetii 应被添加到促进人类 B 细胞非霍奇金淋巴瘤的细菌列表中,可能是通过 pDC 感染和 IL10 过度产生。应考虑在 Q 热患者的管理中筛查早期淋巴瘤诊断,特别是那些持续性局灶性感染的患者。

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