Platelets release proinflammatory microparticles in anti-neutrophil cytoplasmic antibody-associated vasculitis

Rheumatology ◽  
2019 ◽  
Vol 58 (8) ◽  
pp. 1432-1442 ◽  
Author(s):  
Di Miao ◽  
Tian-Tian Ma ◽  
Min Chen ◽  
Ming-Hui Zhao
Keyword(s):  
Renal Damage ◽  
Potential Role ◽  
Biological Functions ◽  
Active Stage ◽  
Array Analysis ◽  
Antibody Microarrays ◽  
Bioactive Proteins ◽  
Anca Associated Vasculitis ◽  
Proinflammatory Molecules

Abstract Objective The biological functions of the platelets contributing to ANCA-associated vasculitis (AAV) are largely unclear. The current study aimed to investigate the potential role of platelet-derived microparticles (PMPs) in AAV. Methods In the current study, microparticles in AAV patients were analysed by flow cytometry, and PMPs were probed for relative levels of 640 bioactive proteins secreted from patients’ platelets using antibody microarrays. These data were then correlated with clinical and pathological parameters. Results PMPs were significantly increased in 69 AAV patients, predominantly MPO-ANCA positive patients in active stage compared with in remission [4406.8/μl (2135.4, 5485.0) vs 549.7/μl (350, 708.5), P < 0.0001], and 43% of microparticles in active AAV were PMPs. Compared with 15 patients in remission, highly expressed proinflammatory molecules in the microparticles from platelets in 15 AAV patients in active stage revealed that potential functions of PMPs were promotion of the effect of chemotaxis, adhesion, growth and apoptosis (all the patients for array analysis were MPO-ANCA positive). The level of PMPs had a significant association with disease activity, inflammation, and renal damage. Conclusion PMPs may serve as inflammatory propagators through their wide production of proinflammatory cytokines in AAV, potentially providing a novel therapeutic target.

scholarly journals P0276SERUM C3 LEVELS AND THE PROGNOSIS OF ANCA-ASSOCIATED VASCULITIS: A SINGLE-CENTER RETROSPECTIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Annalisa Carta ◽  
Elisa Russo ◽  
Leda Cipriani ◽  
Daniela Picciotto ◽  
Michela Saio ◽  
...  
Keyword(s):  
Renal Damage ◽  
Alternative Pathway ◽  
Rapidly Progressive Glomerulonephritis ◽  
Renal Outcome ◽  
Secondary Outcome ◽  
Rank Test ◽  
P Value ◽  
Risk Of Death ◽  
Anca Associated Vasculitis

Figure: Background and Aims Despite improved survival, patients affected by ANCA-associated vasculitis (AAV) presenting with rapidly progressive glomerulonephritis (RPGN) still remain at a higher risk of death relative to the general population. Recent findings suggest a role for the activation of the complement alternative pathway in the pathogenesis of the disease. We aimed to retrospectively evaluate the presentation and outcome of a cohort of patients with AAV and RPGN according to ANCA specificity, investigating the role of complement pathways. Method We retrospectively examined 1,547 biopsies performed between 1996 and 2019 in our center, which included 124 patients presenting with paucimmune RPGN. Patients without ANCA serology and/or with missing data (n=44), ANCA negative RPGN (n=15) and anti-GBM disease (n=2) were excluded from our analysis. Seventy-eight patients with AAV and RPGN (63 biopsy proven) were analysed and compared according to ANCA serotype (n=30 MPO, n=21 PR3). Furthermore, data were analysed on the basis of median levels of serum C3 (1.05 g/l). Statistical analysis Data are mean ± SD or median and interquartile range for variables not normally distributed. Groups were compared using ANOVA after logarithmic transformation of skewed variables. Primary endpoint was renal survival defined as need for renal replacement therapy (NRRT); secondary outcome was patient survival. Cumulative and renal survivals were calculated using Kaplan-Meier method and differences between groups were analysed with the log-rank test. Multivariate Cox proportional hazard analysis for time to NRRT was performed to determine the significance of different risk factors in renal outcome. A p value of &lt; 0.05 was considered statistically significant. Results Patients had a mean age of 64± yrs and eGFR ±15 ml/min at diagnosis. Patients with MPO-AAV were older (69±11 vs. 61±14 yrs, p=0.02) and showed lower levels of C3 (1.0±0.22 vs 1.25±0.2 g/l, p=0.009) as compared to PR3 patients. Moreover, those presenting with C3 levels lower than median value had more advanced renal damage at diagnosis (eGFR 7± ml/min vs 15.5± ml/min, p= 0.04). Serum C3, but not C4 levels, significantly correlated with eGFR, proteinuria and serum uric acid at diagnosis. Twenty-seven (39.7%) reached ESRD requiring RRT. The 1-, 5- and 10- yrs patients renal survivals were 81%, 62.9 % and 52.4%. Renal outcome was neither influenced by ANCA serotype nor gender but patients with C3 levels below median value exhibited a worse renal prognosis (Log rank p=0.02) and a 5 times higher risk of NRRT (HR 5.1, 95% CI 1.4-18.7, p=0.01) independently by potential confounding factors. Conclusion Referral to the nephrologist was late, at an advanced stage of disease, indicating the need to improve the awareness of AAV and RPGN in order to favour early treatment. In this cohort, low C3 indicated a more severe renal damage and predicted poorer renal outcome thus suggesting a role of complement activation in the pathogenesis and progression of these nephritides.

Dicarbonyls Generation, Toxicities, Detoxifications and Potential Roles in Diabetes Complications

2020 ◽  
Vol 21 (9) ◽  
pp. 890-898
Author(s):  
Sultan Alouffi ◽  
Mohd Wajid Ali Khan
Keyword(s):  
Diabetes Complications ◽  
Potential Role ◽  
Depth Information ◽  
Biological Functions ◽  
Advanced Glycation ◽  
Secondary Complications ◽  
Glycation End Products ◽  
Factor Α ◽  
Necrosis Factor

It has been well established that advanced glycation end-products (AGEs) have a strong correlation with diabetes and its secondary complications. Moreover, dicarbonyls, especially, methylglyoxal (MG) and glyoxal, accelerate AGEs formation and hence, have potential roles in the pathogenesis of diabetes. They can also induce oxidative stress and concomitantly decrease the efficiency of antioxidant enzymes. Increased proinflammatory cytokines (tumor necrosis factor-α and interleukin- 1β) are secreted by monocytes due to the dicarbonyl-modified proteins. High levels of blood dicarbonyls have been identified in diabetes and its associated complications (retinopathy, nephropathy and neuropathy). This review aims to provide a better understanding by including in-depth information about the formation of MG and glyoxal through multiple pathways with a focus on their biological functions and detoxifications. The potential role of these dicarbonyls in secondary diabetic complications is also discussed.

scholarly journals TOX as a potential target for immunotherapy in lymphocytic malignancies

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chaofeng Liang ◽  
Shuxin Huang ◽  
Yujie Zhao ◽  
Shaohua Chen ◽  
Yangqiu Li
Keyword(s):  
T Cell ◽  
Potential Role ◽  
Hematological Malignancies ◽  
High Mobility ◽  
High Mobility Group ◽  
Biological Functions ◽  
Hmg Box ◽  
Cell Exhaustion ◽  
Potential Target

AbstractTOX (thymocyte selection-associated HMG BOX) is a member of a family of transcriptional factors that contain the highly conserved high mobility group box (HMG-box) region. Increasing studies have shown that TOX is involved in maintaining tumors and promoting T cell exhaustion. In this review, we summarized the biological functions of TOX and its contribution as related to lymphocytic malignancies. We also discussed the potential role of TOX as an immune biomarker and target in immunotherapy for hematological malignancies.

The potential role of mast cells and fibroblast growth factor-2 in the development of hypertension-induced renal damage

2020 ◽  
Vol 122 (6) ◽  
pp. 151599
Author(s):  
Stancho Stanchev ◽  
Boycho Landzhov ◽  
Georgi Kotov ◽  
Nikola Stamenov ◽  
Tihomir Dikov ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mast Cells ◽  
Fibroblast Growth Factor ◽  
Renal Damage ◽  
Potential Role ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth

The role of the sphingolipid pathway in liver fibrosis: an emerging new potential target for novel therapies

2020 ◽  
Vol 318 (6) ◽  
pp. C1055-C1064 ◽  
Author(s):  
Yuval Ishay ◽  
Dean Nachman ◽  
Tawfik Khoury ◽  
Yaron Ilan
Keyword(s):  
Liver Disease ◽  
Potential Role ◽  
Cellular Membrane ◽  
Biological Functions ◽  
Bioactive Lipids ◽  
Potential Therapeutic Target ◽  
End Stage Liver Disease ◽  
Sphingosine 1 Phosphate ◽  
End Stage

Sphingolipids (SL) are a family of bioactive lipids and a major cellular membrane structural component. SLs include three main compounds: ceramide (Cer), sphingosine (Sp), and sphingosine-1-phosphate (S-1P), all of which have emerging roles in biological functions in cells, especially in the liver. They are under investigation in various liver diseases, including cirrhosis and end-stage liver disease. In this review, we provide an overview on the role of SLs in liver pathobiology and focus on their potential role in the development of hepatic fibrosis. We describe recent evidence and suggest SLs are a promising potential therapeutic target for the treatment of liver disease and fibrosis.

scholarly journals TAFRO Syndrome with Renal Thrombotic Microangiopathy: Insights into the Molecular Mechanism and Treatment Opportunities

2021 ◽  
Vol 22 (12) ◽  
pp. 6286
Author(s):  
Kun-Hua Tu ◽  
Pei-Yi Fan ◽  
Tai-Di Chen ◽  
Wen-Yu Chuang ◽  
Chao-Yi Wu ◽  
...  
Keyword(s):  
Thrombotic Microangiopathy ◽  
Renal Damage ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Renal Involvement ◽  
Vascular Endothelial ◽  
Tafro Syndrome ◽  
Endothelial Growth Factor ◽  
Histopathologic Findings

TAFRO syndrome is an extremely rare form of idiopathic MCD, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy, and organomegaly. Like idiopathic MCD, renal involvement is also a common presentation in patients with TAFRO syndrome. Furthermore, membranoproliferative glomerulonephritis (MPGN)-like injury and thrombotic microangiopathy (TMA) are the most reported histopathologic findings of renal biopsy. Several molecular mechanisms have been previously postulated in order to explain the TAFRO syndrome symptoms, including abnormal production of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. The role of these cytokines in renal injury, however, is not well understood. The aim of this review article is to summarize the latest knowledge of molecular mechanisms behind the TAFRO syndrome and their potential role in renal damage.

scholarly journals The Role of Vitamin D in Diabetic Nephropathy: A Translational Approach

2022 ◽  
Vol 23 (2) ◽  
pp. 807
Author(s):  
Charlotte Delrue ◽  
Reinhart Speeckaert ◽  
Joris R. Delanghe ◽  
Marijn M. Speeckaert
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Renal Damage ◽  
Diabetic Kidney Disease ◽  
Potential Role ◽  
Genetic Mechanisms ◽  
Translational Approach ◽  
Matrix Accumulation

According to several animal and human studies, vitamin D appears to play a significant role in the development of diabetic nephropathy. However, the possible renoprotective effect of vitamin D and its influence on the reversal of already existing renal damage remains doubtful. At this moment, there are a few hypotheses concerning the underlying molecular and genetic mechanisms including the link between vitamin D and inflammation, oxidative stress, and extracellular matrix accumulation. The present review aims to investigate the potential role of vitamin D in the development of diabetic kidney disease from a translational approach.

scholarly journals Renal Chemerin Expression is Induced in Models of Hypertensive Nephropathy and Glomerulonephritis and Correlates with Markers of Inflammation and Fibrosis

2019 ◽  
Vol 20 (24) ◽  
pp. 6240 ◽  
Author(s):  
Alexander Mocker ◽  
Karl F. Hilgers ◽  
Nada Cordasic ◽  
Rainer Wachtveitl ◽  
Carlos Menendez-Castro ◽  
...  
Keyword(s):  
Renal Damage ◽  
Potential Role ◽  
Inverse Relation ◽  
Rt Pcr ◽  
Hypertensive Nephropathy ◽  
Renal Inflammation ◽  
Markers Of Inflammation ◽  
Specific Induction ◽  
Renal Expression

Chemerin and its receptor, chemokine-like receptor 1 (CmklR1), are associated with chemotaxis, inflammation, and endothelial function, especially in metabolic syndrome, coronary heart disease, and hypertension. In humans, circulating chemerin levels and renal function show an inverse relation. So far, little is known about the potential role of chemerin in hypertensive nephropathy and renal inflammation. Therefore, we determined systemic and renal chemerin levels in 2-kidney-1-clip (2k1c) hypertensive and Thy1.1 nephritic rats, respectively, to explore the correlation between chemerin and markers of renal inflammation and fibrosis. Immunohistochemistry revealed a model-specific induction of chemerin expression at the corresponding site of renal damage (tubular vs. glomerular). In both models, renal expression of chemerin (RT-PCR, Western blot) was increased and correlated positively with markers of inflammation and fibrosis. In contrast, circulating chemerin levels remained unchanged. Taken together, these findings demonstrate that renal chemerin expression is associated with processes of inflammation and fibrosis-related to renal damage. However, its use as circulating biomarker of renal inflammation seems to be limited in our rat models.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

Sign in / Sign up

Export Citation Format

Share Document