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It appears that a tick introduces an agent–presumably a spirochete–into the skin (see Fig. 1). Immune complexes form and become systemic during the rash. Some patients (identified by the presence of cryoglobulins containing IgM, Clq-reactive material, and depressed IgG and IgA levels) then alter their immune response and may develop neurologic, cardiovascular, or joint involvement. Despite systemic clearing in some patients, the immune complexes localize to the joints where a chronic synovitis develops, similar to rheumatoid arthritis. Why the immune complexes localize to the joints is an enigma. It is tempting to postulate that this localization occurs because of an altered immune response in a genetically predisposed group. However, three of 10 patients with chronic arthritis did not have the B-cell alloantigen DRw2.