Locating a genetic marker for rheumatic fever using a pedigree analysis

Includes bibliographical references (pages [58]-61)Rheumatic Fever is caused by an autoimmune response to an untreated Group A P-haemolytic Streptococcus pyogenes infection. A rheumatagenic streptococcus contains fimbriae composed of lipoteichoic acid surrounding an M protein. The formation of antibodies to specific streptococcal cell wall components, which have epitopes in common with host tissue, causes a reaction with the host tissues that induces the inflammatory response characteristic of rheumatic fever. Undiagnosed and untreated rheumatic fever can progress to rheumatic heart disease. It is commonly believed that rheumatic fever is a secondary response caused by epitope mimicry in the immune system. The epitopes created during the processing of the M proteins of Streptococcus pyogenes are similar to the exposed surface proteins of cardiac cytoskeletal tropomyosin and the hyaluronic acid in human synovial fluid. Since the late 1800s it has been observed that rheumatic fever runs in families, and more recently it has been suggested that genetic factors contribute to a family’s susceptibility to rheumatic fever. This thesis tested the hypothesis that rheumatic fever is linked with one of the immunoglobulin genes, using a large family in which rheumatic fever is prevalent. The light chain kappa (k ) and lambda (k) isotypes are coded for on the 2nd and 22nd chromosomes respectively, and the nine isotypes of the heavy chain are all coded for on the 14th chromosome. Several microsatellites near the end of these coding regions were tested to see if any were associated with susceptibility to the autoimmune response of rheumatic fever.M.S. (Master of Science