Characterization of Inflammatory Cell Subpopulations of the Gut Associated Lymphoid Tissue and Peripheral Lymph Nodes in Inflammatory Bowel Disease

One of the biggest barriers to progress towards better treatments in
inflammatory bowel disease (IBD) is 1) our lack of understanding of the disease
etiology and 2) our lack of understanding the mechanisms involved in response
or lack/loss of response to treatments, such as the development of anti-drug
antibodies. The gut associated lymphoid tissue (GALT) as well as peripheral
lymph nodes (LN) are lymphoid structures that play an important role in and
antibody formation and are involved in shaping intestinal and peripheral
immunity. It is however unknown whether and how these lymphoid structures are
involved in IBD etiology and whether they are involved in anti-drug antibody
formation. We hypothesize that 1) GALT and peripheral LN are involved in IBD
pathophysiology, and 2) GALT and peripheral LN are involved in anti-drug
antibody formation, and thereby loss of response to therapy.

1) Our first aim is to determine the involvement of GALT (Peyer*s patches,
mesenteric lymph nodes) and peripheral lymph nodes in the immune deregulation
that is observed in IBD

2) Our second aim is to understand the pathophysiological mechanisms in
peripheral lymph nodes of IBD patients in the development of immunogenicity to
therapeutic antibodies.

To achieve these aims we will:
Analyze immunological alteration in mesenteric lymph nodes, Peyers patches
and/or inguinal lymph nodes (including phenotype and function of B- and T
cells, cytokine production, genetic, epigenetic and transcriptional alterations
of immune and stromal cells) of IBD patients, and correlate these alterations
with diagnosis, disease stage, treatment response.

We will perform a cross sectional study for immune cell characterization and
gene expression analysis in the GALT and inguinal lymph node compartments and
lymphoid organs, to elucidate the mechanisms involved in the pathogenesis of
IBD, as well as, in the development of immunogenicity against biological
treatments. Patients with UC and CD will be recruited from the outpatient IBD
clinic at Amsterdam University Medical Centers. Demographic data and clinical
data regarding classification of diagnosis, medication use and disease
activity, will be collected. Patients will be included starting March 2020 with
an inclusion period of 2-3 years.
Since these are pioneering studies in the field of IBD, we will also study
inguinal lymph node biopsy sampling in healthy controls, in order to detect
differences that are specific for IBD patients.

To get access to GALT tissues and mesenteric lymph nodes, IBD patients
undergoing surgery because of extensive inflammation or stenotic disease will
be included in our study. For this procedure we will collaborate with the
gastrointestinal surgery department of the gastroenterology unit. In addition,
we will obtain peripheral (inguinal) lymph node biopsy samples under
ultrasonographic guidance both from IBD patients undergoing surgery as well as
those without surgical treatment.

IBD is a chronic destructive incurable disease, characterized by a medical need
for novel drugs and therapeutic protocols. Furthermore, the application of
personalized medicine approaches on current treatments is necessary, to achieve
a more favourable outcome for the patients, as well as, to improve their
quality of life. Our research will contribute significantly in this goal and
the long-term benefits of the patients definitely outweight the risks of the
individuals involved. Moreover, as it is previously described, the sampling
procedures (blood and lymph node), are accompanied by insignificant adverse
events, and are safe for the subjects. Potential hematomas due to the needle
biopsy or blood withdrawal, are easily addressed with no impact for the health
condition of the individuals.