title: Toll-like receptors in systemic lupus erythematosus: potential for personalized treatment.
abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens. The symptoms of SLE, progression of pathology and the array of autoantibodies present in the serum differ significantly from patient to patient, which calls for a personalized approach to treatment. SLE is polygenic and strongly influenced by gender, ethnicity, and environmental factors. Data from genome-wide association studies suggests that polymorphisms in as many as 100 genes contribute to SLE susceptibility. Recent research has focused on genes associated with Toll-like receptors (TLRs), type I interferons, immune regulation pathways, and immune-complex clearance. TLR7 and TLR9 have been extensively studied using lupus-prone mouse models. In multiple systems overexpression of TLR7 drives disease progression but interestingly, a loss of TLR9 results in an almost identical phenotype. While TLR7 overexpression has been linked to human SLE, the possible role of TLR9 in human disease remains elusive. In the present review, we focus on TLR polymorphisms and TLR expression in SLE patients and discuss their potential as biomarkers for individualized treatment.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (ASTAR) , Singapore, Singapore.
authors.forename: Teja
authors.initials: T
authors.lastname: Celhar
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (ASTAR) , Singapore, Singapore.
authors.forename: Anna-Marie
authors.initials: AM
authors.lastname: Fairhurst
keywords: TLR7; TLR9; pharmacogenomics; systemic lupus erythematosus; type I interferons