The effect of TNFα-blockers on B-cells in patients with granulomatous diseases.

Sarcoidosis and Crohn*s disease are different entities, but are both
characterized by formation of granulomas by a T-cell mediated immune response.
Treatment is often similar, in particular regarding the use of biologicals as
TNFα-blockers. Recent studies indicate maturation disturbances in B-cell in
both in sarcoidosis and Crohn*s disease. However, B-cell maturation patterns
differ between the two diseases, which might indicate a different
immunopathogenesis. TNFα-blockers are increasingly implemented in the treatment
of both diseases, but are expensive, can cause side effects and are not always
successful. It would be valuable to use B-cells as a (predictive) marker for
therapeutic response. We have previously demonstrated that changes in the
numbers of the CD27-IgA+ B-cell subset in blood might indicate therapeutic
response to TNF-blockers in sarcoidosis. We here aim to monitor the blood
B-cell compartment before and during TNF-blockers in patient groups suffering
from two different types of granulomatous disease to increase our understanding
of the immune system and identify biomarkers to predict response to
biologicals.

Primary Objective: To identify new immunological markers for therapeutic
response to anti-TNF therapy in chronic granulomatous diseases.

To study the effect of biological therapy on B-cell maturation, patients with
granulomatous disease such as sarcoidosis and Crohn*s disease who are indicated
for biological therapy, will be included. Patients are not to be prescribed
biologicals specifically for this study. Blood withdrawal will take place in
patients before start and during therapy with TNFα-blockers. To obtain insight
in the pharmacodynamic processes of these agents, B-cell maturation will be
studied four times per patient with a follow up of eight months from start of
therapy.

There are no benefits as it is an observational study. However, the only burden
to this study is extra blood withdrawal when venous punction is already
scheduled, either for regular check-ups, or for therapy with infliximab.