scholarly journals RNA sensing by conventional dendritic cells is central to the development of lupus nephritis

2015 ◽  
Vol 112 (45) ◽  
pp. E6195-E6204 ◽  
Author(s):  
Teja Celhar ◽  
Richard Hopkins ◽  
Susannah I. Thornhill ◽  
Raquel De Magalhaes ◽  
Sun-Hee Hwang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Moderate Increase ◽  
Rna Recognition ◽  
Toll Like Receptor ◽  
Systemic Lupus ◽  
Slow Progression ◽  
Inflammatory Milieu

Glomerulonephritis is a common and debilitating feature of systemic lupus erythematosus (SLE). The precise immune mechanisms that drive the progression from benign autoimmunity to glomerulonephritis are largely unknown. Previous investigations have shown that a moderate increase of the innate Toll-like receptor 7 (TLR7) is sufficient for the development of nephritis. In these systems normalization of B-cell TLR7 expression or temporal depletion of plasmacytoid dendritic cells (pDCs) slow progression; however, the critical cell that is responsible for driving full immunopathology remains unidentified. In this investigation we have shown that conventional DC expression of TLR7 is essential for severe autoimmunity in the Sle1Tg7 model of SLE. We show that a novel expanding CD11b+ conventional DC subpopulation dominates the infiltrating renal inflammatory milieu, localizing to the glomeruli. Moreover, exposure of human myeloid DCs to IFN-α or Flu increases TLR7 expression, suggesting they may have a role in self-RNA recognition pathways in clinical disease. To our knowledge, this study is the first to highlight the importance of conventional DC-TLR7 expression for kidney pathogenesis in a murine model of SLE.

The patient with systemic lupus erythematosus

2015 ◽  
Author(s):  
Johan van der Vlag ◽  
Jo H. M. Berden
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
B Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Heparan Sulphate ◽  
Systemic Lupus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations. The hallmark of SLE is the presence of antibodies against nuclear constituents, such as double-stranded (ds)DNA, histones, and nucleosomes. Local deposition of antinuclear antibodies in complex with nuclear autoantigens induces serious inflammatory conditions that can affect several tissues and organs, including the kidney.The levels of antinucleosome and anti-dsDNA antibodies seem to correlate with glomerulonephritis and these autoantibodies can often be detected years before the patient is diagnosed with SLE. Apoptotic debris is present in the extracellular matrix and circulation of patients with SLE due to an aberrant process of apoptosis and/or insufficient clearance of apoptotic cells and apoptotic debris. The non-cleared apoptotic debris in patients with SLE may lead to activation of both the innate (myeloid and plasmacytoid dendritic cells) and adaptive (T and B cells) immune system. In addition to the activation by apoptotic debris and immune complexes, the immune system in SLE may be deregulated at the level of (a) presentation of self-peptides by antigen-presenting cells, (b) selection processes for both B and T cells, and (c) regulatory processes of B- and T-cell responses. Lupus nephritis may be classified in different classes based on histological findings in renal biopsies. The chromatin-containing immune complexes deposit in the capillary filter, most likely due to the interaction of chromatin with the polysaccharide heparan sulphate. A decreased renal expression of the endonuclease DNaseI further contributes to the glomerular persistence of chromatin and the development of glomerulonephritis.Current treatment of lupus nephritis is not specific and aims to reduce the inflammatory response with general immunosuppressive therapies. However, research has revealed novel potential therapeutic candidates at the level of dendritic cells, B cells, and T cells.

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

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