Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hoc analysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hoc study of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2 or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2 in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

• MeSH
• ANCA-asociované vaskulitidy * patofyziologie   terapie   farmakoterapie   komplikace   imunologie   diagnóza   MeSH
• dospělí MeSH
• glomerulonefritida * patofyziologie   imunologie   terapie   krev   MeSH
• glukokortikoidy * terapeutické užití   aplikace a dávkování   MeSH
• hodnoty glomerulární filtrace * MeSH
• ledviny * patofyziologie   účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obnova funkce MeSH
• senioři MeSH
• výměna plazmy * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• MeSH
• ANCA-asociované vaskulitidy komplikace   terapie   MeSH
• glomerulonefritida * etiologie   terapie   MeSH
• IgA nefropatie farmakoterapie   MeSH
• lidé MeSH
• nefritida při lupus erythematodes farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

A20/Tnfaip3, an early NF-κB response gene and key negative regulator of NF-κB signaling, suppresses proinflammatory responses. Its ubiquitinase and deubiquitinase activities mediate proteasomal degradation within the NF-κB pathway. This study investigated the involvement of A20 signaling alterations in podocytes in the development of kidney injury. The phenotypes of A20Δpodocyte (podocyte-specific knockout of A20) mice were compared with those of control mice at 6 months of age to identify spontaneous changes in kidney function. A20Δpodocyte mice presented elevated serum urea nitrogen and creatinine levels, along with increased accumulation of inflammatory cells-neutrophils and macrophages-within the glomeruli. Additionally, A20Δpodocyte mice displayed significant podocyte loss. Ultrastructural analysis of A20 podocyte-knockout mouse glomeruli revealed hypocellularity of the glomerular tuft, expansion of the extracellular matrix, podocytopenia associated with foot process effacement, karyopyknosis, micronuclei, and podocyte detachment. In addition to podocyte death, we also observed damage to intracapillary endothelial cells with vacuolation of the cytoplasm and condensation of nuclear chromatin. A20 expression downregulation and CRISPR-Cas9 genome editing targeting A20 in a podocyte cell line confirmed these findings in vitro, highlighting the significant contribution of A20 activity in podocytes to glomerular injury pathogenesis. Finally, we analyzed TNFAIP3 transcription levels alongside genes involved in apoptosis, anoikis, NF-κB regulation, and cell attachment in glomerular and tubular compartments of kidney biopsies of patients with various renal diseases.

• MeSH
• cytoskelet * metabolismus   MeSH
• glomerulonefritida * patologie   metabolismus   genetika   MeSH
• glomerulus patologie   metabolismus   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované * MeSH
• myši MeSH
• NF-kappa B metabolismus   MeSH
• podocyty * metabolismus   patologie   MeSH
• signální transdukce MeSH
• TNFAIP3 * metabolismus   genetika   MeSH
• zánět * patologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: To determine differences in the blood innate gene expression signatures of systemic lupus erythematosus (SLE) patients across various organ manifestations and disease activity, with a focus on lupus nephritis (LN) and central nervous system (CNS) involvement. METHODS: Toll-like receptor family (TLR 1-10) mRNA expression was investigated in peripheral blood mononuclear cells from patients with SLE (n = 74) and healthy controls (n = 34). We compared patients with histologically confirmed active LN or neuropsychiatric systemic lupus erythematosus (NPSLE) with patients without these symptoms. The expression of TLR mRNA was determined by RT‒qPCR using a high-throughput SmartChip Real-Time-qPCR system (WaferGen). Multivariate analysis and nonparametric statistics were used for data analysis to assess the associations between TLRs and disease activity and severity. RESULTS: TLR4 (0.044 vs. 0.081, p = 0.012) was upregulated and TLR10 (0.009 vs. 0.006, p = 0.0007) was downregulated in the whole cohort of SLE patients compared to healthy controls. A comparison of the active LN group with participants without kidney involvement revealed increased expression of TLR2 (0.078 vs. 0.03, p = 0.009), and TLR5 (0.035 vs. 0.017, p = 0.03). Moreover, a significant difference was observed in TLR9 expression between inactive LN and the control group (0.014 vs. 0.009, p = 0.01), together with borderline correlation in TLR2 expression (0.04 vs. 0.03, p = 0.06). Receiver operating characteristic (ROC) curve analysis revealed that TLR1 and TLR2 expression were the best potential diagnostic markers for active LN. The NPSLE group showed upregulation of TLR1 (0.088 vs. 0.048, p = 0.01), TLR4 (0.173 vs. 0.066, p = 0.0003) and TLR6 (0.087 vs. 0.036, 0.007). Our correlation analysis supported the close relationships among the expression of individual TLRs in the whole lupus cohort and its subgroups. CONCLUSION: Our study revealed differences in TLR expression between a lupus cohort and healthy controls. Additionally, our analysis provides insight into specific TLR expression in cases with severe organ manifestations, such as LN and NPSLE. The multiple mutual relationships of TLRs demonstrate the activation of innate immunity in SLE and suggest promising targets for future therapies or diagnostics.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nefritida při lupus erythematodes * genetika   krev   MeSH
• systémový lupus erythematodes krev   genetika   MeSH
• toll-like receptory * genetika   biosyntéza   MeSH
• vaskulitida centrálního nervového systému při lupus erythematodes * krev   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biologické markery MeSH
• budesonid škodlivé účinky   MeSH
• glomerulus patologie   MeSH
• IgA nefropatie * diagnóza   farmakoterapie   patologie   MeSH
• imunoglobulin A MeSH
• lidé MeSH
• proteinurie patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• cystická onemocnění ledvin diagnóza   farmakoterapie   klasifikace   MeSH
• diabetické nefropatie diagnóza   farmakoterapie   MeSH
• glomerulonefritida diagnóza   etiologie   farmakoterapie   klasifikace   patologie   MeSH
• infekce močového ústrojí diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• intersticiální nefritida diagnóza   farmakoterapie   klasifikace   MeSH
• nádory ledvin diagnóza   klasifikace   MeSH
• náhrada funkce ledvin klasifikace   metody   MeSH
• nemoci ledvin * diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• urolitiáza diagnóza   etiologie   farmakoterapie   MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• IgA nefropatie * farmakoterapie   MeSH
• imunoglobulin A MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

A proliferation-inducing ligand (APRIL) is a key member of the tumor necrosis factor superfamily of cytokines and plays a central role in B-cell survival, proliferation, and Ig class switching. Recently, there has been increasing interest in the role of APRIL and the related cytokine B-cell activating factor in several glomerular diseases, because of their importance in the above processes. The therapeutic inhibition of APRIL represents a potentially attractive immunomodulatory approach that may abrogate deleterious host immune responses in autoimmune diseases while leaving other important functions of humoral immunity intact, such as memory B-cell function and responses to vaccination, in contrast to B-cell-depleting strategies. In this review, we describe the physiological roles of APRIL in B-cell development and their relevance to glomerular diseases, and outline emerging clinical trial data studying APRIL inhibition, with a focus on IgA nephropathy where the clinical development of APRIL inhibitors is in its most advanced stage.

• MeSH
• B-lymfocyty * imunologie   účinky léků   MeSH
• glomerulus imunologie   patologie   účinky léků   MeSH
• IgA nefropatie * imunologie   farmakoterapie   MeSH
• lidé MeSH
• protein TALL-2 * antagonisté a inhibitory   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

IgA nefropatie je nejčastější primární glomerulonefritida. V patogenezi onemocnění hrají zásadní roli imunitní komplexy, složené z galaktózy-deficitního IgA1 a autoprotilátek, které aktivují komplement a vyvolávají imunitní zánět glomerulů, progredující renální insuficienci až selhání ledvin. V současné době jsou léčebné možnosti u tohoto onemocnění limitované. Nepochybně potřebujeme cílenou léčbu, která ovlivní tvorbu patogenních protilátek obsahujících Gd-IgA1 a imunokomplexů. Tento článek shrnuje nové léčebné možnosti, které zasahují na úrovni vlastní patogeneze IgAN, ovlivňují komplementem zprostředkovaný zánět, tvorbu galaktóza-deficitního IgA1 i patogenních protilátek deplecí B a CD38 pozitivních plazmatických buněk.

IgA nephropathy is the most common primary glomerulonephritis worldwide. Immune complexes, composed of galactose-deficient IgA1 and Gd-IgA1 autoantibodies, are deposited in the mesangial area of the glomeruli where they induce complement-mediated inflammation. This may result in the reduced kidney function which can progress to end stage kidney disease. Treatment options are very limited. Treatments which directly affect the formation of pathogenic Gd-IgA1 antibodies and anti-Gd-IgA1 antibody-containing immune complexes are needed. This article reviews potential therapies that may affect the main axis of pathogenesis of IgA nephropathy. New treatment options are aimed at the immunopathogenesis of IgAN including depletion or modulation of Gd-IgA1 producing B cells, plasma cells, alternate and/or lectin pathway of complement.

• MeSH
• glifloziny farmakologie   terapeutické užití   MeSH
• hormony kůry nadledvin farmakologie   terapeutické užití   MeSH
• IgA nefropatie * diagnóza   farmakoterapie   imunologie   MeSH
• inhibitory ACE farmakologie   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• komplement - faktor B antagonisté a inhibitory   MeSH
• lidé MeSH
• monoklonální protilátky MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

There is no specific treatment for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a disease that is very rare in the pediatric population. We report the case of a 15-year-old boy who presented with mildly reduced kidney function and nephrotic syndrome. Kidney biopsy revealed PGNMID with monoclonal deposits of IgG3 with kappa light chain restriction. Flow cytometry showed a significant CD38 plasma cell population in the peripheral blood in the absence of other signs of hematological malignancy. The patient was treated with a 6-month course of daratumumab, a monoclonal antibody targeting CD38. There was a significant reduction in proteinuria and normalization of kidney function. Based on positive experience with adults, daratumumab should also be studied in children with PGNMID.

• MeSH
• antigeny CD38 imunologie   analýza   MeSH
• biopsie MeSH
• imunoglobulin G * krev   MeSH
• ledviny patologie   imunologie   účinky léků   MeSH
• lidé MeSH
• membranoproliferativní glomerulonefritida * farmakoterapie   imunologie   patologie   MeSH
• mladiství MeSH
• monoklonální protilátky * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH