Periodontitis and Rreumatoid arthritis- association, dual treatment and resolution study

Rheumatoid arthritis and periodontitis are prevalent chronic conditions
associated with significant morbidity. Both conditions are characterized by
chronic inflammation and local tissue destruction. Evidence from our and other
groups indicates that RA and PD not only often concur, but may also have a
shared etiopathogenesis. The production of inflammatory and microbial particles
during PD may enhance arthritogenic immune activation. Furthermore, PD may
induce a break in immune tolerance in genetically predisposed individuals,
resulting in production of the RA-defining anti-citrullinated peptide
antibodies (ACPA) and elevated Th17 subset responses.
It is clinically highly relevant to investigate whether RA disease activity can
be diminished by oral treatment of PD. Current treatment options for PD are
limited, and for RA are not always adequate and associated with
immunosuppressive side effects. Recently, key findings in the mechanisms of
inflammation indicate that resolution of inflammation is steered by biochemical
mediators, termed pro-resolving mediators, that enable inflamed tissue to
return to homeostasis. Oral application of the pro-resolving mediator resolvin
E1 (RvE1) was shown to prevent onset and progression of experimental acute PD.
Of importance and in contrast to immunosuppressants RvE1 increased clearance of
PD-associated bacteria. Therefore, RvE1 is an interesting candidate drug to be
investigated in a new oral treatment modality for the dual treatment of PD and
RA.
Despite the experimental effectiveness of RvE1 for PD, it is unclear whether
periodontal treatment with RvE1 will diminish RA disease activity. On the one
hand, PD may be only involved in the initiation of RA and disease progression
might be driven by PD-independent inflammatory mechanisms. On the other hand,
systemic inflammatory innate and adaptive immune mechanisms may be shared
between inflamed periodontium and synovium independent of the disease phase.
We hypothesize that RA and PD are pathophysiologically linked, and that
periodontal treatment with RvE1 reduces both PD and arthritis by attenuating
the shared adaptive inflammatory response and reducing oral bacterial cell
numbers.

To investigate the pathophysiological link between RA and PD, and test the
efficacy of RvE1 treatment in gingival tissue biopsies of RA-PD and RA risk-PD
patients ex vivo.

Study design: A mechanistic biologic analysis in transversal patient cohorts.

Intervention: questionnaire, blood sampling, gingival tissue biopsy and for RA
patients willing to undergo a second procedure: an ultrasound guided synovial
biopsy.

1. vene punction: In a proportion of persons undergoing vene punction a
hematoma can occur.
2. gingiva biopsy: In a proportion of persons undergoing gingival biopsy a
hematoma can occur.
3. ultrasound guided synovial biopsy: In a proportion of persons undergoing a
synovial biopsy a hematoma can occur.