B-cell non-Hodgkin lymphoma linked to Coxiella burnetii

Abstract

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.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 1 macrophages within both lymphoma and lymphadenitis tissues but localization in CD123 1 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 5 .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. (Blood. 2016;127(1):113-121)

Mouse Model of Coxiella burnetii Aerosolization

“…The bone marrow tropism of C. burnetii observed experimentally could fit with the hematophagocytic syndrome, ring granuloma, and hairy cell leukemia observed in humans (32)(33)(34)(35). Lymph node involvement during Q fever has recently been described in humans as lymphadenitis and lymphoma (36). In the present study, we report early and persistent lymph node C. burnetii detection (qPCR) in both BALB/c and SCID mice.…”

Coxiella burnetii antibody seropositivity is not a risk factor for AIDS-related non-Hodgkin lymphoma

“…Recently, chronic C burnetii infection has been linked to the development of nonHodgkin B-cell lymphoma (NHL). 1 This study of 1468 patients from the French National Referral Center for Q Fever database found a 25-fold increase in the risk of NHL development among Q fever patients relative to the general population. The link between Q fever and NHL development is believed to be related to plasmacytoid dendritic cell infection within lymphoid tumors and interleukin-10 (IL-10) overproduction.…”

“…C burnetii infection of plasmacytoid dendritic cells within lymphoid tissues and IL-10 overproduction support the development of NHL. 1 HIV infection also leads to significantly higher IL-10 serum levels.…”

“…1,2 ALL is characterized by a relatively small number of genomic alterations that disproportionally affect hematopoietic transcriptional factors. 1,3 ALL that arises from the T-cell lineage (T-ALL) vs B-cell lineage has distinctive immunophenotypes and unique genomic abnormalities. 4,5 However, the vast majority of genome sequencing and subsequent mechanistic studies of ALL singularly focus on coding regions and the role of noncoding genomic aberrations in leukemogenesis remains mostly uncharacterized with few exceptions.…”

Chronic Splenic Q Fever?

“…Differential diagnosis with a non-Hodgkin lymphoma should be considered [5]. A prolonged antibiotic treatment at 18 months is necessary.…”