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.
Highlights
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variety of clinical manifestations that differ from patient to patient
We propose altered expression of TLR7/9 as a biomarker for identification of a subset of SLE patients that might benefit from a targeted therapeutic approach
Overall, accumulating data suggest that persistently higher levels of TLR7 may lead to an acquired responsiveness in cells which are normally unresponsive to TLR7 ligands
Summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variety of clinical manifestations that differ from patient to patient. While the diagnostic criteria for SLE have evolved over the past decades (reviewed in Yu et al, 2014), the treatment has remained largely symptomatic using non-specific conventional therapies which include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, hydroxychloroquine (HCQ), and immunosuppressants (Murphy et al, 2013). In addition to their modest therapeutic effect, these drugs have severe side effects leading to substantial morbidity and mortality, resulting in a substantial economic burden to many societies (Lau and Mak, 2009). The B cells have a critical role in autoantibody production due to initial loss of www.frontiersin.org
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