CLINICAL NEWS
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Featured research from recent issues of Blood
PAPER SPOTLIGHT
• 70% (1,028) had
an acute Q fever
without progression
to persistent focalized
infection
• 30% (n=440) had a
persistent focalized
infection – including
4.6 percent (n=68) with
initial acute Q fever
Study Finds Link Between
Non-Hodgkin Lymphoma
and Coxiella Burnetii
Infection
A dry fracture of a Vero cell
exposing the contents of a
vacuole where Coxiella burnetii are busy growing. Source:
National Institute of Allergy
and Infectious Diseases.
ASHClinicalNews.org
Coxiella burnetii (C.
burnetii), the bacterium
that causes Q fever, is associated with a more than
25-fold increase in the risk
of developing diffuse large
B-cell lymphoma (DLBCL),
according to a study conducted by Cléa Melenotte,
MD, of Aix-Marseilles
Université in Marseilles,
France, and colleagues.
“Bacterial infections
play a role in the development of some B-cell
non-Hodgkin lymphomas,
either by inhibition of
immune function or by
induction of chronic inflammatory response,” Dr.
Melenotte and co-authors
wrote. “Several lymphoid
disorders have been
reported in the course
of Q fever … Lymphoma,
however, was previously
considered to be a risk factor of persistent Q fever
rather than a consequence
of the infection.”
In the current study, Dr.
Melenotte and researchers
screened 1,468 consecutive patients who were
enrolled in the French National Referral Center for
Q Fever database between
January 2004 and December 2014, identifying patients who had developed
lymphoma after C. burnetii
primary infection to assess a possible excess risk
of B-cell lymphoma in Q
fever patients. They then
tested the presence of the
bacterium in lymphoma
biopsies, evaluated interleukin-10 (IL10) production
in Q fever patients with
lymphoma, and investigated whether patients
with persistent focalized
infection were more at
risk for lymphoma than
acute Q fever patients.
Patients were followed until as late as
March 2015. Standardized incidence ratios were
computed to confirm any
increased risk of developing DLBCL and follicular
lymphoma (FL) in patients
with Q fever compared
with the French general
population.
Of the 1,468 patients
(mean age = 50.5 years):
Seven patients (0.48%)
had a diagnosis of B-cell
NHL after C. burnetii primary infection (mean age
= 62.4 years), all of whom
presented with mature
B-cell NHL. Six patients
had DLBCL (standardized
infection ratio [SIR] =
25.4; 95% CI 11.4-56.4) and
only one patient was diagnosed with FL (SIR=6.7;
95% CI 0.9-47.9).
Using immunofluorescence and fluorescence in
situ hybridization (FISH),
C. burnetii was detected
in CD68+ macrophages
within both lymphoma
and lymphadenitis tissues. However, localization in CD123+ plasmacytoid dendritic cells
(pDCs) was found only in
lymphoma tissues. Infection of pDCs, therefore,
may represent a critical
step toward the development of lymphoma.
Patients with Q fever
with persistent focalized infection were at
an increased risk for
lymphoma compared
with patients without
known progression to
persistent focalized
infection (hazard ratio =
9.35; 95% CI 1.10-79.4).
In addition, IL-10 overproduction was found
in patients developing
lymphoma (p=0.0003).
“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,”
Dr. Melenotte and coauthors explained.
“Patients with Q
fever are at significantly
higher risk to develop
lymphoma and should be
followed to detect abnormal lymph nodes as
soon as possible,” Didier
Raoult, MD, PhD, corresponding author on the
study, told ASH Clinical
News. “Chronic infection
in phagocytic cells may
develop in a lymph node
and may trigger lymphoma. This is probably
linked to immunodepression caused by IL10
secreted during Q fever
when it is persistent.”
One limitation of the
study is its small sample
size, and the researchers
noted that larger studies are needed to confirm
that the risk of lymphoma
occurrence among patients with Q fever does
not involve precursor
lymphoid neoplasms or
T-cell lymphomas.
“Although we cannot
conclude that Q fever
directly causes lymphoma,
our results are unlikely
to be due to chance
since several criteria for
causation are fulfilled,”
the authors concluded.
“Additional reports of
cases treated by antibiotics alone would provide
greater support for the
purported association.”
The link between Q
fever and lymphoma,
however, “should not
be neglected since early
diagnosis of lymphoma
could result in improved
outcomes for Q fever patients [and] the management of patients with
B-cell NHL could be improved by the detection
of C. burnetii infection in
endemic areas.”
REFERENCES
Melenotte C, Million M, Audoly G, et al. B-cell
non-Hodgkin lymphoma linked to Coxiella
burnetii. Blood. 2015 October 13. [Epub ahead
of print]
ASH Clinical News
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