Hypothesis two: Immune-mediated disorder An unknown antigen stimulates the immune system, resulting in systemic production of IgM antibody and altering native IgG. The IgG/Anti IgG and the antigen/IgM complexes then become fixed in synovial tissue, and are linked with complement. Neutrophils are chemotactically attracted to the site, engulf the complexes, die in the joint and release enzymes, resulting in inflammation. Inflammatory mediators, such as cytokines and prostaglandins, cause pain, as well as upregulating epithelial expression of adhesion molecules, and causing chondrocytes to produce more degradative enzymes. Over time, the affected joints begin to erode, causing instability, deformity and laxity upon physical exam. Clinical signs typically appear in small and toy breeds during early adulthood.