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.
This study directly examines a potential susceptibility gene for a number of human autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis. The protein molecule encoded by this gene may represent an important target for the therapy of these human diseases.
|Della Torre, E; Mattoo, H; Mahajan, V S et al. (2014) Prevalence of atopy, eosinophilia, and IgE elevation in IgG4-related disease. Allergy 69:269-72|
|Della-Torre, Emanuel; Mattoo, Hamid; Mahajan, Vinay S et al. (2014) IgG4-related midline destructive lesion. Ann Rheum Dis 73:1434-6|
|Mattoo, Hamid; Mahajan, Vinay S; Della-Torre, Emanuel et al. (2014) De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol 134:679-87|
|Ahmad, Maimuna; Mahajan, Vinay S; Mattoo, Hamid et al. (2014) Individuals with IgG4-related disease do not have an increased frequency of the K409 variant of IgG4 that compromises Fab-arm exchange. J Rheumatol 41:185-7|
|Mattoo, H; Della-Torre, E; Mahajan, V S et al. (2014) Circulating Th2 memory cells in IgG4-related disease are restricted to a defined subset of subjects with atopy. Allergy 69:399-402|
|Kai, Xin; Chellappa, Vasant; Donado, Carlos et al. (2014) I?B kinase ? (IKBKB) mutations in lymphomas that constitutively activate canonical nuclear factor ?B (NF?B) signaling. J Biol Chem 289:26960-72|
|Chellappa, Vasant; Taylor, Kendra N; Pedrick, Kathryn et al. (2013) M89V Sialic acid Acetyl Esterase (SIAE) and all other non-synonymous common variants of this gene are catalytically normal. PLoS One 8:e53453|
|Kalay, Ersan; Sezgin, Orhan; Chellappa, Vasant et al. (2012) Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome. Am J Hum Genet 90:76-85|
|Hirschfield, G M; Xie, G; Lu, E et al. (2012) Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes. Genes Immun 13:328-35|
|Pillai, Shiv; Netravali, Ilka Arun; Cariappa, Annaiah et al. (2012) Siglecs and immune regulation. Annu Rev Immunol 30:357-92|
Showing the most recent 10 out of 13 publications