title: B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.
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.
authors.affiliation: 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;
authors.forename: Cléa
authors.initials: C
authors.lastname: Melenotte
authors.affiliation: 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;
authors.forename: Matthieu
authors.initials: M
authors.lastname: Million
authors.affiliation: 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;
authors.forename: Gilles
authors.initials: G
authors.lastname: Audoly
authors.affiliation: Service de Médecine Interne, Nouvel Hôpital Civil, Strasbourg, France;
authors.forename: Audrey
authors.initials: A
authors.lastname: Gorse
authors.affiliation: Service de Maladies Infectieuses et Tropicales, Groupe Hospitalier Pellegrin, Bordeaux, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Dutronc
authors.affiliation: Service de Radiologie, Hôpital Nord, Marseille, France;
authors.forename: Gauthier
authors.initials: G
authors.lastname: Roland
authors.affiliation: Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel;
authors.forename: Michal
authors.initials: M
authors.lastname: Dekel
authors.affiliation: Service of Infectious Diseases, Hospital Clinic of Barcelona, Institut Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain;
authors.forename: Asuncion
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Service de Médecine Nucléaire, Hôpital de la Timone, Marseille, France;
authors.forename: Serge
authors.initials: S
authors.lastname: Cammilleri
authors.affiliation: Aix Marseille Université, INSERM, UMR912 (Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM]), IRD, Marseille, France; Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France;
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Carrieri
authors.affiliation: Aix Marseille Université, INSERM, UMR912 (Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM]), IRD, Marseille, France; Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France;
authors.forename: Camelia
authors.initials: C
authors.lastname: Protopopescu
authors.affiliation: Centre Henri Becquerel, Institut de Recherche et d'Innovation Biomédicale, INSERM, U918, Rouen, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruminy
authors.affiliation: 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; Laboratoire d'Anatomopathologie, Hôpital de la Timone, Marseille, France;
authors.forename: Hubert
authors.initials: H
authors.lastname: Lepidi
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, Marseille, France;
authors.forename: Bertrand
authors.initials: B
authors.lastname: Nadel
authors.affiliation: 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;
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Immunity and Cancer, INSERM, U1068, Marseille, France; and Department of bio-pathology, Institut Paoli Calmettes, Marseille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.affiliation: 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;
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016997:Coxiella burnetii / Q000235:genetics / Q000472:pathogenicity*; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011778:Q Fever / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D012307:Risk Factors
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10