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MRI and Quantification of Draining Lymph Node Function in Inflammatory Arthritis
Author(s) -
PROULX STEVEN T.,
KWOK EDMUND,
YOU ZHIGANG,
BECK CHRISTOPHER A.,
SHEALY DAVID J.,
RITCHLIN CHRISTOPHER T.,
BOYCE BRENDAN F.,
XING LIANPING,
SCHWARZ EDWARD M.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.016
Subject(s) - arthritis , synovitis , medicine , lncap , lymph node , magnetic resonance imaging , lymphatic system , tumor necrosis factor alpha , lymph , pathogenesis , rheumatoid arthritis , inflammation , inflammatory arthritis , pathology , endocrinology , radiology , cancer , prostate cancer
: While erosion and tissue necrosis are the end‐stage result of inflammatory arthritis, factors that can predict their initiation and severity are unknown. In an effort to identify these prognostic factors we developed contrast‐enhanced (CE)‐magnetic resonance imaging (MRI) for the mouse knee to assess the pathogenesis of inflammatory arthritis. Using this approach to study synovitis and draining lymph node (LN) function we first demonstrated that the LNs of TNF‐Tg mice at 5 months are significantly larger and have greater enhancement in comparison to wild‐type (WT) mice. This difference correlated with the abundance of dilated LYVE‐1+ sinuses in the draining LNs. Dynamic CE‐MRI further demonstrated differences between TNF‐Tg and WT mice in the kinetics of LN enhancement. We established an LN capacity (LNcap) measurement that is a function of both volume and CE. We demonstrated that TNF‐Tg mice have a 15‐fold increase over WT levels at 5 months age ( P < 0.001). Amelioration of arthritis with anti‐TNF therapy resulted in a significant decrease in LNcap ( P < 0.0001) that approached WT levels within 4 weeks. Interestingly, this functional decrease was not associated with a reduction of lymphatic vessels, which persist after therapy in both LNs and synovium. To assess the relationship between draining LN function and synovitis, a regression analysis was performed that demonstrated a significant negative correlation ( R 2 = 0.63, P = 0.01) between LNcap and synovial volume. TNF‐Tg mice with a lower LNcap display an accelerated progression of arthritis. These results indicate a protective function of enhanced lymphatic drainage in inflammatory arthritis.