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The Expression and Clinical Significance of Toll-like Receptor 9 on Blood B Cell and Renal Tissue in Patients with Lupus Nephritis

Author: ShiXiaoFei
Tutor: LiuZhangSuo；LiuShengYun
School: Zhengzhou University
Course: Internal Medicine
Keywords: Toll-like receptor (TLR) Toll-like receptor 9 (TLR9) Lupus nephritis (LN) CpG-DNA Systemic lupus erythematosus (SLE)
CLC: R593.242
Type: Master's thesis
Year: 2007
Downloads: 238
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Abstract

Background and purpose of systemic lupus erythematosus (Systemic Lupus Erythematosus, SLE) based on autoreactive T and B cell activation abnormalities produce pathogenic autoantibodies and immune complexes is the main feature of a chronic inflammatory autoimmune disease , the body can affect multi-system, multi-organ, the kidney is one of the most common organ involved. So far unknown pathogenesis of lupus nephritis (Lupus Nephritis, LN), the severity of a direct impact on SLE prognosis, about 10% to 25% of patients develop end-stage renal failure, to become one of the major cause of death for SLE. Toll-like receptors (toll-like receptors, TLRs) are natural immune important pathogen recognition receptors to identify the pathogen associated molecular patterns (pathogen associated molecular pattern, PAMP)-induced immune effector molecule expression, activation of multiple proinflammatory factor involved in the anti-infective process. Recent study found TLRs corresponding to specific ligands (including endogenous and exogenous ligands) to promote cell surface expression of costimulatory molecules and MHC-II molecules, enhanced APC antigen-presenting; addition, the process of secreting Th1-type cytokines such as IFNs, IL-6, IL-12, and D of NF-a direct regulation of CTL, B cells and other immune cells mature and function, participate in, and regulation of the specific immune response in innate immunity and specificity immune to bridge the gap between. Thus, TLRs correlation with autoimmune diseases growing concern. TLR9 due to specifically recognize bacterial DNA and immune complexes of non-methylated CpG-DNA sequence, a member of the TLR family, to start the MyD88-dependent signal transduction pathway is activated by a cascade reaction the transcription factor NF-κB, AP-1, etc., produce large amounts of proinflammatory cytokines and activation of immune cells, participation and mediated B cell activation, proliferation and antibody production, play an important role in autoimmune and inflammatory process, it is the researchers speculate CpG-DNA/TLR9 signaling pathways may closely related to the pathogenesis of SLE and LN. Of TLR9 in-depth study will further elucidate the pathogenesis of lupus disease activity and organ damage, as well as the potential role of infection in the pathogenesis of, but also to provide new ideas for treatment. This study were to investigate the relationship between intracellular flow cytometry and immunohistochemistry method to detect peripheral blood B lymphocytes in patients with lupus nephritis and renal tissue expression of TLR9 and analysis with disease activity, organ function and other clinical indicators TLR9 potential mechanism and its clinical significance in LN. [Methods] (1) use of intracellular flow cytometry detected 39 cases of confirmed LN patients and 18 healthy peripheral blood CD19-B lymphocytes TLR9 expression, and in patients with LN SLE disease activity index (SLEDAI) Grading is divided into the active phase and inactive groups, respectively, compared TLR9 expression differences between groups B cells. In addition, expression of TLR9 SLEDAI, complement C3 level correlation analysis. (2) using immunohistochemistry confirmed 57 cases of LN patients with renal biopsy tissue, and 11 patients with normal renal tissue TLR9 detection analysis, according to the ISN / RPS pathological type and differences in the level of expression of TLR9 also comparison. In addition, expression of TLR9 kidney histopathological indicators, clinical laboratory parameters correlation analysis. Results (1) active LN patients (SLEDAI score ≥ 10) peripheral blood CD19 ~ B cells TLR9 expression than in non-active LN patients and normal control group (P <0.01), but not in patients with active LN B cell TLR9 expression rate was higher than the normal control group, but not statistically significant (P> 0.05); active LN patients applied to small and medium-dose hormone and (/ or) immunosuppressants TLR9 no expression of CD19 ~ B cells significant effect (P> 0.05). (2) LN peripheral blood of patients with the CD19 ~ B cell the TLR9 expression rate SLEDAI score was positively correlated (P <0.01); no significant correlation (P> 0.05) and serum C3 levels. (3) normal renal tissue glomerular or a very small amount of TLR9 expression in renal interstitial cells express only a small amount of infiltration. Compared with normal kidney tissue, kidney tissue of patients with various types of LN glomerular and renal interstitial TLR9 expression than those of normal kidney tissue increased (P <0.05), mainly expressed in the cells of the renal involvement and TLR9 expression and type of renal pathology the severity of Ⅳ LN renal tissue ISN / RPS TLR9 expression levels than Ⅱ, Ⅲ, Ⅴ was significantly higher (P <0.01). (4) organization LN patients with renal glomerular TLR9 expression levels of glomerular cell proliferation degree LN renal pathological activity index (AI) was positively correlated (P <0.01); renal interstitial TLR9 expression levels of AI in renal The quality of the extent of damage are positively correlated (P <0.01). (1) LN patients with renal tissue glomerular TLR9 expression level of estimated glomerular filtration rate (eGFR) was negatively correlated (P <0.01), and 24-hour urinary protein excretion exists a positive correlation (P <0.05), related (P> 0.05) and serum complement C3 level; while renal qualitative TLR9 expression level and eGFR were negative related (P <0.01), and 24-hour urinary protein excretion complement body C3 levels had no correlation (P> 0.05) . [Conclusion] (1) TLR9 in LN patients with peripheral blood B cells upregulated, suggesting that TLR9 involved in the abnormal activation of B cells in patients with LN and LN abnormal immune process. (2) TLR9 expression in renal tissue of patients with LN higher expression level LN renal pathology in patients with damage severity. (3) TLR9 expression levels in peripheral blood B cells in the renal tissue as a judgment LN disease activity, the degree of renal dysfunction and clinical prognosis indicator.

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CLC: > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Lupus erythematosus > Lupus nephritis
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