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B-cell non-Hodgkin lymphoma linked to Coxiella burnetii

Cléa Melenotte, Matthieu Million, Gilles Audoly, Audrey Gorse, Hervé Dutronc, Gauthier Roland, Michal Dekel, Asuncion Moreno, Serge Cammilleri, Maria Patrizia Carrieri, Camelia Protopopescu, Philippe Ruminy, Hubert Lepidi, Bertrand Nadel, Jean-Louis Mege, Luc Xerri and Didier Raoult

Key points

  • Coxiella burnetii is associated with an increased risk of lymphoma, its presence in the tumor microenvironment may favor lymphomagenesis.

  • Lymphoma has to be considered in patients with Q fever and lymphoid disorders, especially those with persistent focalized infections.

Abstract

Bacteria can induce human lymphomas, while 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 two diseases. We screened 1,468 consecutive patients of the 2004-2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIR) 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 rRNA 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 to 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 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.

  • Submitted April 9, 2015.
  • Accepted September 6, 2015.