Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Brucellosis-Induced Murine Arthritis and Spondylolisthesis.
Lyons1, Elizabeth T., Magnani2, Diogo, Forde1, Toni S., Splitter2, Gary, Adarichev1, Vyacheslav A.
Approximately 500,000 people world-wide are infected with Brucella each year and most develop spondyloarthropathy by mechanisms which are poorly understood. Brucellosis is a zoonotic disease that remains endemic to many parts of the world and therefore presents a problem for public health due to possible transmission to domestic animals and humans. The goal of the study was to establish a murine model for human Brucellosis to better understand mechanisms of association between Brucella infection and spondylitis of lumbar and sacral spine in human patients.
BALB/c females were infected via i.p. injection with 100M B.abortus S19 or B.melitensis GR023, then sacrificed 3 and 26 weeks post-infection. Bacterial dissemination was monitored using bioluminescence and histopathology. Axial skeleton from thoracic to tail, front and hinds paws, spleen, and liver were included in the evaluation. Histopathology slides were stained with hematoxylin & eosin, alcian blue, tartrate-resistant acid phosphatase. Immunohistochemistry was performed for IBA-1 marker and Brucella cell wall.
B.abortus and B.melitensis demonstrated similar peaks of bacterial infection at day seven, but bacteria remained detectable in the intraperitoneal cavity, spleen, and skeletal tissues for several weeks post-infection. In vivo bioluminescence showed accumulation of luminescent B.melitensis in tarsal parts of front and hind paws and in knees, but the strongest signal was detected in the tail following the distribution of vertebrae. Upon immunohistochemical staining, intracellular bacteria were found in the spleen, liver, epiphysis and metaphysis of peripheral joints, as well as in the subchondral region of vertebrae. Three weeks post-infection, bacteria-infected cells were not found in the peridiscal space or in the joint cavity, but were located in the subchondral bone. Though bacteria could be seen in association with cartilaginous structures, infiltration by inflammatory cells was undetectable. At 26 weeks post-infection with Brucella spp, infected cells were not found in spleen and subchondral bone, but were visible only as a weak and very rare staining of granulomas in liver. Despite the general absence of infection at this time point, mice developed arthritis in ankle joints, spondylolisthesis, and torsion/rotation misalignment in caudal spine.
Acute infection with B.melitensis or B.abortus is not associated with arthritis or spondyloartyhropathy in this murine model. Inflammation in joints and changes in skeleton were found at later time weeks after the bacteria were already cleared from subchondral bone marrow. Therefore, Brucella-induced osteomyelitis demonstrated features which are typical to reactive arthritis.
To cite this abstract, please use the following information:
Lyons, Elizabeth T., Magnani, Diogo, Forde, Toni S., Splitter, Gary, Adarichev, Vyacheslav A.; Brucellosis-Induced Murine Arthritis and Spondylolisthesis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2096