- Primary membranous nephropathy presenting with crescentic glomerulonephritis 25 years after initial presentation: A case report . [Journal Article]
- CNClin Nephrol 2018 Jun 22
- Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Rarely, it can present with rapidly-progressive renal failure and hematuria. While this may be due to lupus nephritis, superimpose...
Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Rarely, it can present with rapidly-progressive renal failure and hematuria. While this may be due to lupus nephritis, superimposed anti-glomerular basement membrane (GBM) disease, or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, there have been rare reports of anti-GBM - and ANCA-negative crescentic glomerulonephritis presenting in primary membranous nephropathy (pMN). We present the case of a patient with long-standing pMN who developed acute deterioration of renal function and was found to have a flare of MN along with crescentic glomerulonephritis (GN) despite a negative serum ANCA, anti-GBM, and antinuclear antibody (ANA) work-up. He was started on dialysis and immunosuppressive therapy, and eventually recovered enough renal function to become dialysis-independent. A brief review of available literature suggests that crescentic GN presenting with pMN is a rare but established entity. Much more rarely has it been reported to occur in patients with previously-diagnosed pMN. In these contexts, crescentic GN may be occurring as the most severe manifestation of pMN rather than as a separate entity. Immunosuppressive therapy is often given, however, prognosis is guarded as half of patients will have worsening renal function and a quarter will develop end-stage renal disease. .
- Anti-neutrophil extracellular trap antibody in a patient with relapse of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report. [Journal Article]
- BNBMC Nephrol 2018 Jun 22; 19(1):145
- CONCLUSIONS: The collective findings suggest NET induction potential of ANETA in the present patient and that the ANETA could contribute to the enhancement of NETs resulting in amplification of the ANCA-NETs vicious cycle.
- Microscopic polyangiitis presented with biopsy-confirmed pleuritis. [Journal Article]
- MAMonaldi Arch Chest Dis 2018 Jun 21; 88(2):897
- We describe a case of microscopic polyangiitis manifested as pleuritis confirmed by thoracoscopic biopsy. An 80-year-old man presented with a three-day history of shortness of breath and cough. Chest...
We describe a case of microscopic polyangiitis manifested as pleuritis confirmed by thoracoscopic biopsy. An 80-year-old man presented with a three-day history of shortness of breath and cough. Chest radiography revealed patchy opacities in the lower fields of the bilateral lung and right-sided pleural effusion. Thoracentesis revealed lymphocytic pleural exudates. Thoracoscopic biopsy specimens were compatible with fibrotic pleuritis. He developed rapidly progressive glomerulonephritis with elevated myeloperoxidase anti-neutrophil cytoplasmic antibody titer in blood and pleural effusion. Although the patient was resistant to two weekly courses of pulse steroid therapy, he was successfully treated with a five-day course of intravenous immunoglobulin.
- C-terminal truncation of IFN-γ inhibits proinflammatory macrophage responses and is deficient in autoimmune disease. [Journal Article]
- NCNat Commun 2018 Jun 20; 9(1):2416
- Controlled macrophage differentiation and activation in the initiation and resolution of inflammation is crucial for averting progression to chronic inflammatory and autoimmune diseases. Here we show...
Controlled macrophage differentiation and activation in the initiation and resolution of inflammation is crucial for averting progression to chronic inflammatory and autoimmune diseases. Here we show a negative feedback mechanism for proinflammatory IFN-γ activation of macrophages driven by macrophage-associated matrix metalloproteinase 12 (MMP12). Through C-terminal truncation of IFN-γ at 135Glu↓Leu136 the IFN-γ receptor-binding site was efficiently removed thereby reducing JAK-STAT1 signaling and IFN-γ activation of proinflammatory macrophages. In acute peritonitis this signature was absent in Mmp12 -/- mice and recapitulated in Mmp12 +/+ mice treated with a MMP12-specific inhibitor. Similarly, loss-of-MMP12 increases IFN-γ-dependent proinflammatory markers and iNOS+/MHC class II+ macrophage accumulation with worse lymphadenopathy, arthritic synovitis and lupus glomerulonephritis. In active human systemic lupus erythematosus, MMP12 levels were lower and IFN-γ higher compared to treated patients or healthy individuals. Hence, macrophage proteolytic truncation of IFN-γ attenuates classical activation of macrophages as a prelude for resolving inflammation.
- Krüppel-like factor 4 is a negative regulator of STAT3-induced glomerular epithelial cell proliferation. [Journal Article]
- JIJCI Insight 2018 Jun 21; 3(12)
- Pathologic glomerular epithelial cell (GEC) hyperplasia is characteristic of both rapidly progressive glomerulonephritis (RPGN) and subtypes of focal segmental glomerulosclerosis (FSGS). Although ini...
Pathologic glomerular epithelial cell (GEC) hyperplasia is characteristic of both rapidly progressive glomerulonephritis (RPGN) and subtypes of focal segmental glomerulosclerosis (FSGS). Although initial podocyte injury resulting in activation of STAT3 signals GEC proliferation in both diseases, mechanisms regulating this are unknown. Here, we show that the loss of Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, enhances GEC proliferation in both RPGN and FSGS due to dysregulated STAT3 signaling. We observed that podocyte-specific knockdown of Klf4 (C57BL/6J) increased STAT3 signaling and exacerbated crescent formation after nephrotoxic serum treatment. Interestingly, podocyte-specific knockdown of Klf4 in the FVB/N background alone was sufficient to activate STAT3 signaling, resulting in FSGS with extracapillary proliferation, as well as renal failure and reduced survival. In cultured podocytes, loss of KLF4 resulted in STAT3 activation and cell-cycle reentry, leading to mitotic catastrophe. This triggered IL-6 release into the supernatant, which activated STAT3 signaling in parietal epithelial cells. Conversely, either restoration of KLF4 expression or inhibition of STAT3 signaling improved survival in KLF4-knockdown podocytes. Finally, human kidney biopsy specimens with RPGN exhibited reduced KLF4 expression with a concomitant increase in phospho-STAT3 expression as compared with controls. Collectively, these results suggest the essential role of KLF4/STAT3 signaling in podocyte injury and its regulation of aberrant GEC proliferation.
- TLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus. [Journal Article]
- ARAnn Rheum Dis 2018 Jun 20
- CONCLUSIONS: These findings demonstrate a pathogenic role of TLR4+CXCR4+ PCs in the development of lupus nephritis and may provide new therapeutic strategies for the treatment of SLE.
- A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis. [Journal Article]
- BIBMC Immunol 2018 Jun 20; 19(1):18
- CONCLUSIONS: Our research cross contrasts several immunoprotein IF intensities and relevant serum levels in three kinds of primary glomerular nephritis, and finally acquired helpful results for understanding the relationships between pathological presentation and serological presentation of immunoproteins in kidney diseases. Furthermore, this pilot study is offering a possible method for the analysis of combination of pathology and serology.Different pathological types of nephritis presented different expression patterns of immunoglobulin and complement, especially IgA and IgG, which suggested different pathogenesis involved in the development of IgAN and MN. Furthermore, either in tissue or in serum, increased IgA level was closely related with renal function in all of the patients.
- Intrarenal Toll-like receptor 4 and Toll-like receptor 2 expression correlates with injury in anti-neutrophil cytoplasmic antibody associated vasculitis. [Journal Article]
- AJAm J Physiol Renal Physiol 2018 Jun 20
- In anti-neutrophil cytoplasmic antibody associated vasculitis (AAV), toll like receptors (TLRs) may be engaged by infection associated patterns and by endogenous danger signals, linking infection and...
In anti-neutrophil cytoplasmic antibody associated vasculitis (AAV), toll like receptors (TLRs) may be engaged by infection associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4 and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4 and TLR9, with TLR4 being the most prominent in both compartments. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression, and the intensity of glomerular TLR2 expression inversely correlated with the presenting eGFR. While myeloid cells within the kidney expressed TLR2, TLR4 and TLR9, TLR2 and TLR4 co-localized with endothelial cells and podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional relevance of intrarenal TLR expression was further supported by the co-localization of TLRs with their endogenous ligands high mobility group box 1 and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 expression and their correlation with renal injury indicates that TLR4, and to a lesser degree TLR2, may be potential therapeutic targets in this disease.
- An inhibitor of spleen tyrosine kinase suppresses experimental crescentic glomerulonephritis. [Journal Article]
- IJInt J Immunopathol Pharmacol 2018 Jan-Dec; 32:2058738418783404
- Non-selective inhibitors of spleen tyrosine kinase (SYK) efficiently suppress disease in T cell-dependent models of crescentic glomerulonephritis. However, the therapeutic potential of selective SYK ...
Non-selective inhibitors of spleen tyrosine kinase (SYK) efficiently suppress disease in T cell-dependent models of crescentic glomerulonephritis. However, the therapeutic potential of selective SYK inhibitors in this disease has not been established. In addition, we lack knowledge regarding SYK expression in non-myeloid cells in glomerulonephritis. We addressed these two issues in a rat model of nephrotoxic serum nephritis (NTN) using a SYK inhibitor, GS-492429. Disease was induced in Sprague-Dawley rats (Study 1) or Wistar-Kyoto (WKY) rats (Study 2) by immunization with sheep IgG and administration of sheep anti-rat nephrotoxic serum. Animals were untreated or received GS-492429 (30 mg/kg/bid) or vehicle treatment from 2 h before nephrotoxic serum injection until being killed 3 or 24 h later (Study 1) or 14 days later (Study 2). Two-colour confocal microscopy found that SYK expression in NTN kidney was restricted to myeloid cells and platelets, with no evidence of SYK expression by T cells, mesangial cells, podocytes or tubular epithelial cells. In Study 1, GS-492429 treatment significantly reduced glomerular neutrophil and macrophage infiltration, with protection from glomerular thrombosis and proteinuria. In Study 2, GS-492429 treatment reduced glomerular crescent formation by 70% on day 14 NTN in conjunction with reduced glomerular thrombosis, glomerulosclerosis and tubular damage. This was accompanied by a marked reduction in markers of inflammation (CCL2, TNF-α, NOS2, MMP-12). Importantly, the protective effects of GS-492429 were independent of T cell infiltration and activation and independent of JAK/STAT3 signalling. In conclusion, this study demonstrates that a SYK inhibitor can suppress the development of crescentic glomerulonephritis through effects upon myeloid cells and platelets.
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- Fibrillary Glomerulonephritis in a Patient with Sjogren's Syndrome. [Journal Article]
- CCureus 2018 Apr 15; 10(4):e2483
- Fibrillary glomerulonephritis (FGN) is an uncommon cause of primary glomerular disease. FGN is usually idiopathic; however, it has been associated with underlying malignancy or autoimmune diseases in...
Fibrillary glomerulonephritis (FGN) is an uncommon cause of primary glomerular disease. FGN is usually idiopathic; however, it has been associated with underlying malignancy or autoimmune diseases in some patients as well. The most commonly found autoimmune diseases in FGN patients include Graves' disease, systemic lupus nephritis, Chron's disease, and idiopathic thrombocytopenia purpura. FGN in a patient with underlying asymptomatic Sjogren's syndrome is very rare in the literature, with only two previously reported cases of this association. We present the case of a 75-year-old female with a past medical history of asymptomatic primary Sjogren's syndrome and fibromyalgia, who presented to emergency department with a new episode of hypertension. The electron microscopy (EM) showed randomly arranged nonamyloid fibrillar deposits in the mesangium and glomerular capillary walls, confirming FGN. In this case-based review, we describe in detail the diagnostic work-up, clinical course, and complications in management. We also discuss some of the other nonamyloid fibrillary glomerular diseases.