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2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Weiwei Kong ◽  
Yaomin Wang ◽  
Huiping Wang ◽  
Qin Zhou ◽  
Jianghua Chen ◽  
...  

Abstract Background Systemic sclerosis (SSc) may overlap with other connective tissue diseases, which is named overlap syndrome. Scleroderma renal crisis (SRC) is a rare but severe complication of SSc. SSc related thrombotic microangiopathy (SSc-TMA) is an infrequent pathology type of SRC, while SSc-TMA accompanied by overlap syndrome is very rare. Case presentation This study reported a case of acute kidney injury (AKI) accompanied with overlap syndrome of SSc, systemic lupus erythematosus (SLE) and polymyositis (PM). The renal pathology supported the diagnosis of SSc-TMA but not SLE or PM-related renal injury, characterized by renal arteriolar thrombosis, endothelial cells edema, little cast in tubules and mild immune complex deposition. The primary TMA related factors (ADAMTS13 and complement H factor) were normal. Thus, this case was diagnosed as secondary TMA associated with SSc. The patient was treated with renin angiotensin system inhibitors, sildenafil, supportive plasma exchange/dialysis, and rituximab combined with glucocorticoids. After 2 months of peritoneal dialysis treatment, her renal function recovered and dialysis was stopped. Conclusion This study presented a case of SSc-TMA with overlap syndrome. Rituximab can be used as a treatment option in patients with high SRC risk or already manifesting SRC.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Giancarlo R. Valiente ◽  
Armin Munir ◽  
Marcia L. Hart ◽  
Perry Blough ◽  
Takuma T. Wada ◽  
...  

AbstractThe gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. To explore the role of the GM in lupus nephritis, we colonized NZM2410 mice with Segmented Filamentous Bacteria (SFB). Gut colonization with SFB was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition and interstitial inflammation compared to NZM2410 mice free of SFB. With SFB colonization mice experienced an increase in small intestinal lamina propria Th17 cells and group 3 innate lymphoid cells (ILC3s). However, although serum IL-17A expression was elevated in these mice, Th17 cells and ILC3s were not detected in the inflammatory infiltrate in the kidney. In contrast, serum and kidney tissue expression of the macrophage chemoattractants MCP-1 and CXCL1 were significantly elevated in SFB colonized mice. Furthermore, kidney infiltrating F4/80+CD206+M2-like macrophages were significantly increased in these mice. Evidence of increased gut permeability or “leakiness” was also detected in SFB colonized mice. Finally, the intestinal microbiome of SFB colonized mice at 15 and 30 weeks of age exhibited dysbiosis when compared to uncolonized mice at the same time points. Both microbial relative abundance as well as biodiversity of colonized mice was found to be altered. Collectively, SFB gut colonization in the NZM2410 mouse exacerbates kidney disease, promotes kidney M2-like macrophage infiltration and overall intestinal microbiota dysbiosis.


2022 ◽  
Vol 12 ◽  
Author(s):  
Rajkumar Venkatadri ◽  
Vikram Sabapathy ◽  
Murat Dogan ◽  
Rahul Sharma

Lupus glomerulonephritis (LN) is a complex autoimmune disease characterized by circulating autoantibodies, immune-complex deposition, immune dysregulation and defects in regulatory T cell (Tregs). Treatment options rely on general immunosuppressants and steroids that have serious side effects. Approaches to target immune cells, such as B cells in particular, has had limited success and new approaches are being investigated. Defects in Tregs in the setting of autoimmunity is well known and Treg-replacement strategies are currently being explored. The aim of this minireview is to rekindle interest on Treg-targeting strategies. We discuss the existing evidences for Treg-enhancement strategies using key cytokines interleukin (IL)-2, IL-33 and IL-6 that have shown to provide remission in LN. We also discuss strategies for indirect Treg-modulation for protection from LN.


Author(s):  
Tala Pourlak ◽  
Sonya Sharifi ◽  
Sepideh Zununi Vahed ◽  
Elham Ahmadian ◽  
Magali Cucchiarini

Abstract Membranous glomerulonephritis (MGN) is the most common cause of adulthood nephrotic syndrome. Diagnosis of membranous nephritis is based on light electron immunofluorescence microscopy and clinical signs. Immune complex deposition against podocyte antigens such as phospholipase A2 receptor (PLA2R) activates the complement system. Of this, complement Component C4d (C4d) is involved in the classical and lectin pathways. This marker may be used by immunohistochemistry to diagnose MGN when other methods are not available. In this work, C4d expression was monitored by immunohistochemical analysis in the glomerular capillaries of patients with primary MGN (study group, N=33) versus patients with minimal change disease (MCD, control group, N=20) in a cross-sectional evaluation performed based on the diagnosis confirmed by light microscopy and immunofluorescence. There was no significant demographic difference between the two groups except for age (P=0.002). C4d immune-expression was positive in glomerular capillary (2+ to 4+) in most of the MGN patients, while it was negative in the MCD group. The sensitivity and specificity of C4d immunostaining were 95% and 100%, respectively. The Pearson correlation coefficient was 0.74 between C4d (immunohistochemistry) and immunoglobulins (IgG; immunofluorescence) and 0.65 between C4d (immunohistochemistry) and the C3 complement product (immunofluorescence). Immunohistochemical evaluation of C4d is, therefore, a sensitive and specific method that has a high correlation with IgG immunofluorescence.


Lupus ◽  
2021 ◽  
pp. 096120332110625
Author(s):  
Valentina Papa ◽  
James Brainer ◽  
Kammi J Henriksen ◽  
Giovanna Cenacchi ◽  
Anthony Chang

Background Lupus nephritis (LN) is a common manifestation and a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. It is characterized by glomerular and often extraglomerular immune complex deposition. Purpose Given the emerging importance of the tubulointerstitial compartment, we conducted a retrospective study of 78 LN biopsies to enumerate the spectrum of extraglomerular immune complex deposition that can be observed in lupus nephritis by electron microscopy and to identify possible clinical or pathologic correlates. Results The presence of tubulointerstitial immune complex deposition often accompanied interstitial inflammation, but some discrepancies were also seen. Conclusions As target antigens are identified, correlation with glomerular, tubulointerstitial, and vascular immune complex deposition will be of increasing interest.


2021 ◽  
Vol 32 (11) ◽  
pp. 2777-2794
Author(s):  
Janina Müller-Deile ◽  
Nina Sopel ◽  
Alexandra Ohs ◽  
Victoria Rose ◽  
Marwin Gröner ◽  
...  

BackgroundAutoantibodies binding to podocyte antigens cause idiopathic membranous glomerulonephritis (iMGN). However, it remains elusive how autoantibodies reach the subepithelial space because the glomerular filtration barrier (GFB) is size selective and almost impermeable for antibodies.MethodsKidney biopsies from patients with iMGN, cell culture, zebrafish, and mouse models were used to investigate the role of nephronectin (NPNT) regulating microRNAs (miRs) for the GFB.ResultsGlomerular endothelial cell (GEC)-derived miR-192-5p and podocyte-derived miR-378a-3p are upregulated in urine and glomeruli of patients with iMGN, whereas glomerular NPNT is reduced. Overexpression of miR-192-5p and morpholino-mediated npnt knockdown induced edema, proteinuria, and podocyte effacement similar to podocyte-derived miR-378a-3p in zebrafish. Structural changes of the glomerular basement membrane (GBM) with increased lucidity, splitting, and lamellation, especially of the lamina rara interna, similar to ultrastructural findings seen in advanced stages of iMGN, were found. IgG-size nanoparticles accumulated in lucidity areas of the lamina rara interna and lamina densa of the GBM in npnt-knockdown zebrafish models. Loss of slit diaphragm proteins and severe structural impairment of the GBM were further confirmed in podocyte-specific Npnt knockout mice. GECs downregulate podocyte NPNT by transfer of miR-192-5p–containing exosomes in a paracrine manner.ConclusionsPodocyte NPNT is important for proper glomerular filter function and GBM structure and is regulated by GEC-derived miR-192-5p and podocyte-derived miR-378a-3p. We hypothesize that loss of NPNT in the GBM is an important part of the initial pathophysiology of iMGN and enables autoantigenicity of podocyte antigens and subepithelial immune complex deposition in iMGN.


2021 ◽  
pp. 088506662110465
Author(s):  
Andrew Greenway ◽  
Nicole Leahy ◽  
Lisa Torrieri ◽  
Anjile An ◽  
Sarah A. Fink ◽  
...  

Objective: To characterize skin integrity among coronavirus disease 2019 (COVID-19) patients treated in the intensive care unit (ICU), and identify risk factors for skin failure (SF) in these patients. Design: The characteristic, profound pro-inflammatory, hypercoagulable state of COVID-19 is manifested by the high severity of illness and extensive organ dysfunction observed in these patients. SF in critically ill patients, although described previously, exhibits a uniquely complex pathogenesis in this population. Patients: Retrospective review of all COVID-19 patients (confirmed positive for severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) admitted to a single surgical ICU for at least 48 hours between March-June 2020. Interventions: Data were extracted from a COVID-19 institutional data repository that harvested data from electronic health records and other clinical data sources. Demographics; coagulation/inflammation biomarkers; number, location, and stage of SF lesions; resource utilization; and outcomes were captured. Measurements and Main Results: 64 patients met inclusion criteria; 51 (80%) developed SF (SF+ ). Forty-three (85%) developed stage 3 or higher SF (χ2  =  22.66, P < .0001). Thirty-nine of 51 (76%) SF+ patients developed more than one SF lesion (χ2  =  13.26, P  =  .0003). SF+ patients manifested a profound pro-inflammatory, hypercoagulable phenotype (lower serum albumin and higher ferritin, interleukin [IL]-6 and D-dimer concentrations [all, P < .001]). Durations of mechanical ventilation, vasopressor therapy, and ICU length of stay were significantly longer (all, P < .05) in the SF + patients. Conclusions: The unique characteristics of COVID-19 dermatopathology and the strong correlation between markers of inflammation and development of SF reflect COVID-19-related organ dysfunction and its deleterious effects on the microcirculation. Considering that skin is invaded directly by SARS-CoV-2 and affected by COVID-19-related immune complex deposition and microthrombosis, SF may reflect disease as opposed to pressure injuries related to processes of care. In the context of COVID-19 critical illness, SF should not be considered a “never event.”


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin-hui Wang ◽  
Rui Lang ◽  
Qin Zeng ◽  
Ying Liang ◽  
Nan Chen ◽  
...  

AbstractJianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.


2021 ◽  
pp. 004947552110412
Author(s):  
Minu P Sunny ◽  
C Krishnan ◽  
PR Sabeel Abdulla ◽  
MG Geeta

Congenital syphilis occurs due to trans-placental transmission of Treponema pallidum or rarely, intrapartum contact with infectious lesions. Even though preventable, congenital syphilis occurs sporadically in India, owing to lack of antenatal screening as well as the lack of awareness among clinicians about the burden of syphilis in the community. Since a significant overlap of clinical manifestations exists with many systemic diseases, awareness among clinicians is crucial for an early diagnosis. Renomegaly, nephrotic syndrome and nephritis can all be the signs of renal involvement in congenital syphilis, which can provide clues of the diagnosis. Direct invasion by spirochetes, hypersensitivity reactions and immune complex deposition in glomeruli contribute to the pathogenesis. We report a case of congenital syphilis characterised by delayed diagnosis with renal as well as cutaneous manifestations from missed maternal syphilis during the antenatal period and owing to the lack of antenatal screening.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tianqi Tu ◽  
Xueling Wei ◽  
Yue Yang ◽  
Nianrong Zhang ◽  
Wei Li ◽  
...  

Abstract Background Common subtypes seen in Chinese patients with membranous nephropathy (MN) include idiopathic membranous nephropathy (IMN) and hepatitis B virus-related membranous nephropathy (HBV-MN). However, the morphologic differences are not visible under the light microscope in certain renal biopsy tissues. Methods We propose here a deep learning-based framework for processing hyperspectral images of renal biopsy tissue to define the difference between IMN and HBV-MN based on the component of their immune complex deposition. Results The proposed framework can achieve an overall accuracy of 95.04% in classification, which also leads to better performance than support vector machine (SVM)-based algorithms. Conclusion IMN and HBV-MN can be correctly separated via the deep learning framework using hyperspectral imagery. Our results suggest the potential of the deep learning algorithm as a new method to aid in the diagnosis of MN.


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