Lymph nodes in pre-clinical and clinical arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting
the joints. RA is thought of as an autoimmune disease although its exact
aetiology is unknown. Different inflammatory pathways have been suggested to be
involved in the pathogenesis of RA. Elevation of CRP, serum cytokines,
chemokines, and RA-specific antibodies precede clinical manifestations of RA.
So far, no RA specific antigen has been identified. Several pathogenetic
theories however, involve antigen presentation as an initiator of the
inflammatory process. It is suggested that this initial inflammatory response
might take place in the secondary lymphoid tissues such as lymph nodes. In
animal models changes in lymph node cellular composition are observed in the
latency phase of arthritis. Based on these data we think that studying lymph
node cellular composition and functioning in pre-clinical and early arthritis
will increase our understanding of the pathogenesis of RA if compared to lymph
node tissue of healthy donors without RA-specific antibodies and without
arthritis.

To investigate LN cellular composition and functional aspects of lymphnodes in
pre-clinical patients eventually developing RA compared to patients that do not
develop RA, and of lymphnodes of early RA patients compared to non-RA patients,
all compared to lymph node tissue in healthy donors, in order to better
understand pathogenetic processes leading to the development of clinical
manifest RA and perpetuation of chronic inflammation.

Procedures:
In addition to the current pre-synoviomics and synoviomics protocol the
patient will undergo histological needle biopsy of an inguinal lymph node. The
lymph node will first be localised by ultrasonography and marked by the
radiologist. A histological biopsy will be performed under local anaesthetics,
lymph node samples will be collected and stored according to standard
procedures for the analysis with different techniques.
In the follow up period this procedure will be repeated after one year, after
development of arthritis, and after reaching remission defined according to the
ACR criteria.
At baseline 10 ml of blood will be drawn in the arthritis patients
(synoviomics) to analyse signaling molecules which might be involved in the
immune activation.

The healthy controls will at baseline undergo histological needle biopsy of an
inguinal lymph node (procedure as described before) and 73 ml of blood will be
drawn for determining the presence of IgM-rheumatoid factor and anti-CCP
antibodies and analysis of signaling molecules.
There will be no follow-up of the healthy controls.

The risk of developing a hematoma after the biopsy is about 4 %. The patient
will visit our outpatient clinic several times. Total duration: 6 hours
For the healthy controls the total study duration will be 1,5 hours.