Evaluate the Relationship between Toll-Like Receptor Activities and Development, Disease Activity and Risk of Major Infections in Patients with Systemic Lupus Erythematosus

  • Huang, Jing-Long (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Systemic lupus erythematosus (SLE) is one of major autoimmune diseases in human which often lead to serious morbidity and mortality. SLE is characterized by autoantibodies directed against self-antigens and resulted in intense inflammation and multiple organ damage. There is evidence that environmental as well as genetic factors may be implicated in the disease pathogenesis of SLE. The short-term and long-term outcome of patients with SLE depend on the severity of SLE disease activity (major organs involved) and possible major infectious complications, such as CNS infection, bacteremia, septic arthritis and osteomyelitis. The optimal treatment of SLE is crutial and usually according to the activity and severity of SLE. Serum complement levels (C3, C4, and CH50), autoantibodies and function test of organs have been used to monitor the severity and activity of SLE, although many reports doubt the acuity. Other possible parameter for SLE activity is necessary. Pattern recognition receptors (PRR) are the key to innate immune system recognition of microbes. The receptors which respond to molecular motifs common to pathogens may also prove to be the weakness that results in autoimmunity, such as SLE. The most important PRR family of receptors involved in lupus, namely the Toll-like receptors (TLRs), can recognize microbial components, including DNA and RNA. Some studies showed that innate immune recognition plays a key role in the initial development and amplification of the immune response to both nucleic acid nucleic binding autoantigens. The nucleic acid binging TLRs appear to play pivotal roles in SLE. The effects of TLR activation in various immune cells (autoantibodies) and IFN, TNF-α, IL-6 production) are clearly implicated in SLE pathogenesis. The aims of this study are designed to evaluate the difference of innate immunity including Toll-like receptor (TLR) signaling (1) between the SLE patients and normal control; (2) between SLE patients with severe infection and without severe infection; and (3) between SLE patients with active disease activity and inactive phase. The specific aims of this project are summarized as below: First year (1) To analyze the major infectious complications of patients with SLE. (2) To evaluate the disease activity and severity of SLE after different treatment regimens. (3) To evaluate the neutrophil function in SLE patients with or without severe infections and controls. (4) To compare Toll-like receptors activity after stimulation between SLE patients and normal controls Second year (1) To correlate the relationships between disease activity of SLE and TLR activity. (2) To monitor the relationship between disease-onset severity (SLEDAI) of SLE and TLR activity. (3) To study the differences of TLR genomics between SLE patients and normal controls. (4) To study the influence of TLR genomics in the disease severity of SLE. (5) To evaluate the relationship among TLR genomics, TLR activity and major infections of SLE patients. (6) To differentiate the TLR activity in SLE patients during disease-flare and infections. Third year (1) To study the possible signaling and transcriptional factors of TLR in SLE activity. (2) To compare IL-12/23-IFN-γ mediated immunity and Toll-like receptor signaling in SLE patients with or without major infections complications and normal control. (3) To correlate the relationship between Toll-like receptor activity and genomics in SLE patients with or without major infections complications. (4) To evaluate the Toll-like receptor activity of dendritic cells.

Project IDs

Project ID:PC9902-1700 
External Project ID:NSC98-2314-B182-002-MY3
StatusFinished
Effective start/end date01/08/1031/07/11

Keywords

  • Systemic lupus erythematosus (SLE)
  • Toll-like receptors (TLRs)
  • innate_x000d_ immunity
  • neutrophil function
  • severity
  • infection
  • gemonics 

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