Tu152 - Senescence Associated DNA Damage in Lymph Node and Synovial Tissue Biopsies of Early Rheumatoid Arthritis Patients

Tuesday, June 21, 2022

6:15 PM – 7:45 PM PT

Presenting Author(s)

AO

Aoife M. O'Byrne, MSc

PhD Candidate
Amsterdam University Medical Centre
Amsterdam, Noord-Holland, Netherlands

Co-Author(s)

Td

Tineke A. de Jong, MSc

PhD Candidate
Amsterdam University Medical Centre
Amsterdam, Noord-Holland, Netherlands
PK

Przemek M. Krawczyk, MSc PhD

Principal Investigator
Amsterdam University Medical Centre
Amsterdam, Overijssel, Netherlands
RH

Ron A. Hoebe, BSc

Core Facility Manager/Scientist
Amsterdam University Medical Centre
Amsterdam, Noord-Holland, Netherlands
Lv

Lisa G.M. van Baarsen, PhD

Associate Professor
Amsterdam University Medical Centre
Amsterdam, Noord-Holland, Netherlands

Increased DNA damage is a physiological hallmark of senescence which has been observed alongside dysfunctional DNA repair machinery in T cells of patients with Rheumatoid Arthritis (RA). T cells closely interact with resident stromal cells within lymph node and synovium tissue, an interaction that might play an important role in initiating chronic inflammation. We hypothesize that DNA damage is already present in synovial and lymph node stromal cells as well as T cells before clinical inflammation presents itself as a result of cellular senescence. A cohort of RA patients and RA-risk individuals underwent ultrasound guided lymph node and synovial tissue biopsies. Biopsies were analyzed by immunofluorescence staining for T cells, stromal cells and the DNA damage marker, gamma H2AX which accumulates at double stranded DNA breaks. Preliminary analysis shows the presence of DNA damage in both stromal cells and T cells within synovial tissue sections of RA patients as well as RA-risk individuals. In line with this, ex-vivo expanded synovial and lymph node stromal cells from RA-risk and RA patients also displayed the presence of DNA damage at higher levels when compared with stromal cells from healthy individuals.. DNA damage is already present in RA-risk individuals before development of clinical inflammation. It is interesting to postulate whether DNA damage correlates with future arthritis development and what effect possible DNA damage in lymphoid organs may have on the break in tolerance observed in RA.