Mutations in the SIAE Gene and Susceptibility to Autoimmune Diseases

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Program Director/Principal Investigator (Last, First, Middle): 1R01AI076505 - 01A2 PI Name: PILLAI, SHIV S ABSTRACT An enzyme that modifies sialic acid moieties known as Sialic acid acetyl esterase regulates the strength of signaling from the antigen receptor on B lymphocytes. Mutation of this gene in mice leads to enhanced B cell receptor signaling and autoimmunity - the mice develop a lupus like syndrome. Mutations in this esterase have been found at a high frequency in patients with autoimmunity. These loss of function variants are relatively common in patients with systemic lupus erythematosus and rheumatoid arthritis among other conditions, but are infrequent in controls. We seek to assess the frequency of these mutations in large numbers of patients and controls, examine families to determine how penetrant these mutations are and examine the mechanisms by which these mutations cause disease. The actual oligomeric structure of the enzyme will be determined and the possibility that mutations function in a dominant negative manner will be examined in cell line based studies.