Page 1276 - Veterinary Immunology, 10th Edition

chemokines, C5a, leukotriene B , and platelet-activating factor,
VetBooks.ir results in the accumulation of neutrophils in the synovial fluid.
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Phagocytosis of immune complexes and tissue debris leads to

protease escape and the release of oxidants. IL-1, IL-17, and TNF-α
stimulate cartilage degradation by activating fibroblast-like cells
that line the synovia and by stimulating the release of

metalloproteases. Metalloprotease-2 and metalloprotease-9 from
chondrocytes and macrophages are increased in canine RA joint
fluid and can degrade the articular cartilage and ligaments.
Activated platelets may enter the joint space and aggravate the
process by producing more IL-1. More importantly, IL-17, TNF-α,

and high mobility group box protein-1 (HMGB1) from activated T
cells activate bone-destroying osteoclasts. Collectively these
reactions lead to bone and cartilage erosion and the characteristic

joint pathology.
Macrophage cytokines also trigger synovial angiogenesis.
Circulating lymphocytes, home to newly formed capillaries,
emigrate into the tissues and aggregate around the blood vessels.
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These infiltrating lymphocytes are primarily activated CD4 T cells.
B cell emigration into the tissues eventually leads to local RF
production. The RFs form immune complexes and activate
complement. Some immune complexes may precipitate out within

the superficial layers of the articular cartilage.
The progressive development of inflammation within synovia
leads first to morning stiffness. The joints become warm as the
blood flow increases, but because the inflammation is restricted to
the synovia, the skin rarely becomes red. The animal may show

depression and fatigue as a result of the systemic effects of IL-1 and
TNF-α. If the joints develop effusions, they will be obviously
swollen. As the disease progresses, the inflamed synovia invades

the cartilage, ligaments, and bone, and destroys the articular
cartilage. Synovial lining cells, small blood vessels, and fibroblasts
proliferate. Large numbers of macrophages are found in the
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pannus, as well as MHC class II B cells and dendritic cells.

Diagnosis.

Diagnosis of rheumatoid arthritis in animals is based on the criteria
established for human rheumatoid arthritis. They are listed in Box

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