The pathogenesis of B-cell non-Hodgkin lymphoma after exposure to C. burnetii: a micro-array study to unravel the genetic pathway

In prior studies, an association between infection with C. burnetii (the
causative agent of Q fever) and non-Hodgkin lymphoma (NHL) was established.
There are several potential explanations for this association. The most
intuitive explanation for this association is that C. burnetii induces
development of non-Hodgkin lymphoma, B-cell NHL specifically. During infection
with C. burnetii, the production of specific cytokines is strongly stimulated.
One of those cytokines is interleukin-10 (IL-10). This cytokine stimulates
B-cell proliferation and prevents apoptosis. The promoting of B-cells could
lead to development of lymphoma, B-NHL specifically. In one study, IL-10 levels
were found to be strongly increased in patients with B-cell NHL and Q fever.
However, currently, the evidence to conclude a causal relationship is
insufficient. Moreover, the pathophysiological pathway remains unclear.
Confirmation of causality and clarification of this pathway will provide
answers for all patients that were affected by Q fever. Moreover, it may
provide leads for intervening in this process. Therefore, we set out to
identify the pathway through which C. burnetii induces NHL. The main outcome
will be the genetic profiles of peripheral blood mononuclear cells.

To clarify the pathophysiological genetic pathway of the association between C.
burnetii and NHL

This study is a laboratory study, designed as an observational cross-sectional
cohort study. After informed consent, we will perform one single venepuncture
during which four EDTA tubes of four milliliters blood will be obtained. We
offer to plan this venepuncture either in the Jeroen Bosch Hospital (at a time
conventient for the patients), which may be combined with any other planned
venepuncture; or to plan this venepuncture at home if patients find that more
conventient. After obtaining the blood, we will isolate peripheral blood
mononuclear cells (PBMC's). These PBMC's will be stored at minus 80 degrees
Celsius, remaining material is destroyed. The cells will be transported at
minus 80 degrees Celsius to Nijmegen, where the micro-array will be performed.

We will perform one single venepuncture that may be combined with venepunctures
that are performed in routine care. If patients prefer, we can perform the
venepuncture at their homes, after making an appointment. Moreover, we ask
patients if we may use their clinical medical data that is stored in
electronical medical records at the Jeroen Bosch Hospital. Since the blood
withdrawal will be performed only once, during which a volume of 16 millilitres
is extracted, there is no risk. The burden consists of venepuncture, occupation
of their time (to perform the venepuncture) and reading the patient informed
consent and information forms. There is no benefit for the patients themselves,
perhaps apart from increasing their understanding of the pathophysiology of
their disease. There is no other group of patients that we can use to study
this association.