ANCA associated vasculitis is a relapsing disease; the role of regulatory B cells

Granulomatosis with polyangiitis (Wegener*s granulomatosis) and microscopic
polyangiitis are systemic autoimmune diseases characterized by inflammation of
bloodvessels. Patients can experience arthritis, coughing and nose bleeds, but
also renal failure, neurological complaints and even fatal pulmonary hemorrhage
can occur. Current treatment with immunosuppressants succeeds in establishing
disease remission in most patients. However, 50% of patients experience a
disease flare. Each flare is accompanied by increased organ damage and loss of
quality of life. Certain patient groups are at increased risk for a flare, but
in individual patients it is it difficult to accurately predict who will
experience a relapse and when.
In the aforementioned diseases autoantibodies (i.e. ANCA) play a major role.
The autoantibodies are directed against constituents of white blood cells and
cause inflammation of small blood vessels. These autoantibodies are produced by
plasma cells that originate from B cells. B cells can be activated by T cells.
Much research has been performed on the role of T cells in regulating the
immune response, however, recent evidence suggests that B cells also have an
important regulatory function by the production of IL-10, a substance capable
of suppressing other immune cells.
Work from our group has demonstrated that a low amount of Il-10 measured in
patients with quiescent disease is associated with an increased risk of a
disease flare in the months thereafter. Very recently, we have shown that B
cells from some patients can actively produce ANCA in vitro. Patients who
produce ANCA with this assay are at increased risk for relapse as well.
Moreover, we found a negative correlation between the number of regulatory B
cells and the amount of produced ANCA. These data strongly suggest that disease
flares are linked to a lack of B cell regulation. In the current proposal, we
aim to investigate the frequency and functionality of regulatory B cells in
ANCA associated vasculitis patients and study the various extra- and
intracellular pathways involved. In addition, we will study in vitro ANCA
production in these patients prospectively and determine whether this aids in
the prediction of disease relapses.

Our overall objective is to better understand the role of regulatory B cells in
disease pathogenesis and to better predict disease flares in order to
individualize treatment.

Patients with ANCA associated vasculitis will be prospectively followed every 3
to 6 months with blood tests. In this blood we will check the number and
functionality of the regulatory B cells. These data will be linked to the
relapses occuring in these patients during the investigational period. Next to
this we will also collect other parameters which can have a relation with the
function of regulatory B cells. This include genetic information, such as
polymorphisms, but also analysis of other lymphocytes, cytokines, inflammatory
proteins and (auto)antibodies. These data will be compared with healthy
controls, disease controls and with patients who experience a relapse.

Extra blood withdrawal at an already planned venapuncture.