Publications by authors named "Dejan Dobi"

Background: In late 2019, the World Health Organization declared Coronavirus disease 2019 a global emergency. Since then, many vaccines have been developed to combat the pandemic. Millions of people have received one of the approved COVID-19 vaccines; unfortunately, some adverse events also have been recorded.

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Background: Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV- recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV- recipients.

Methods: An analysis of 68 (34 HIV+, 34 HIV-) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings.

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Article Synopsis
  • End-stage renal disease (ESRD) increases the risk of developing renal cell carcinoma (RCC), and this study analyzed the characteristics of RCC found in ESRD patients.
  • A total of 34 tumors from 31 ESRD patients were examined, revealing a median age of 56 years, with clear cell RCC being the most common subtype.
  • The findings suggest a favorable prognosis for RCC in ESRD patients, with no tumor-specific deaths reported during the study period.
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The most severe alterations in Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection are seen in the lung. However, other organs also are affected. Here, we report histopathologic findings in the liver and detection of viral proteins and RNA in COVID-19 autopsies performed at the Semmelweis University (Budapest, Hungary).

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Background: Concomitant occurrence of anti-GBM disease and anti-PLA2R positive membranous nephropathy have been previously described. However, to the best of our knowledge, this is the first case report that documents the co-occurrence of the diseases proven by both serologic and histologic methods.

Case Presentation: A 51-year-old woman presented to hospital with nausea, bilateral lower extremity edema, dyspnea, dark urine, and then anuria.

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Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells.

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Systematic registration and examination of biopsy-related data in Central and Eastern Europe are scarce, while the health condition of the population is worse compared to other more developed countries. We aim to create a database and analyze the distribution and temporal variation of the renal biopsy diagnoses in Hungary, including the effect of the recent coronavirus pandemic. The diagnoses were standardized according to the recommendation of the European Renal Association.

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From March through December 2020, 100 autopsies were performed (Semmelweis University, Budapest, Hungary), with chart review, of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrated by real-time reverse-transcription polymerase chain reaction testing (mean age, 74.73 years, range 40-102 years; 50 males, mean age 71.96 years, and 50 females, mean age 77.

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Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and personalized therapies for diseases. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate three-dimensional (3-D) molecular atlases of healthy and diseased kidney biopsies by using multiple state-of-the-art omics and imaging technologies across several institutions. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single-cell level or in 3-D space is a significant challenge that can be a futile exercise if not well controlled.

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Article Synopsis
  • Belatacept shows better long-term outcomes compared to traditional calcineurin inhibitors (CNI) for organ transplant immunosuppression, but has higher rates of early T cell-mediated rejection (TCMR), affecting its overall adoption.
  • A study analyzed kidney biopsies from 92 patients, focusing on gene expression and inflammation to understand how belatacept affects immune responses compared to CNI treatment.
  • The findings revealed a strong correlation between TCMR gene expression and inflammatory levels, highlighting a unique impact of belatacept on myeloid cells and B-cell activity during early rejections.
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  • - The study introduces a new method called multiplex in situ hybridization (ISH) combined with immunofluorescence (IF), referred to as mIFISH, for better detection of cytokines in kidney transplant biopsies.
  • - mIFISH can pinpoint the cellular sources of key cytokines and chemokines and allows for the quantitative measurement of their expression at the single-cell level.
  • - This technique enhances understanding of immune responses and damage in transplanted kidneys, potentially leading to better diagnostics and treatment for transplant recipients.
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  • There is a pressing need for affordable and efficient methods to routinely assess transplant biopsies, utilizing existing collections of FFPE tissue from transplant centers to improve graft outcome predictions.* -
  • Researchers developed assays to evaluate 19 specific target genes in renal allograft biopsies to distinguish between stable graft function and acute rejection, using gene expression analysis from 163 biopsies and further validation with 40 additional samples.* -
  • The study compared two gene expression platforms (QPCR and NanoString), finding that increased expression levels from the target genes correlated with acute rejection and inflammation, providing a valuable tool for clinical assessment of kidney transplants.*
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Background: The role of the soluble urokinase plasminogen activator receptor (suPAR) in focal segmental glomerulosclerosis (FSGS) as the circulating factor or as a predictor of recurrence after transplantation remains controversial. Previously published studies in mice and isolated podocytes produced conflicting results on the effect of suPAR on podocyte injury, effacement of foot processes, and proteinuria. These discordant results were in part due to diverse experimental designs and different strains of mice.

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Introduction: Studies are needed to assess the quality of transcriptome analysis in paired human tissue samples preserved by different methods and different gene amplification platforms to enable data comparisons across experimenters.

Methods: RNA was extracted from kidney biopsies, either submerged in RNA-stabilizing solution (RSS) or stored in formalin-fixed, paraffin-embedded (FFPE) blocks. RNA quality and integrity were compared.

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Article Synopsis
  • Persistent HIV tissue reservoirs hinder efforts to find a cure, making it crucial to identify infected cell types in tissues.
  • The study introduces a new method combining multiplexed in situ hybridization (ISH) and immunofluorescence (IF) for detecting HIV DNA and RNA in human tissues, enabling precise assessment of infection.
  • The authors also explore how different tissue fixatives affect the detection of HIV signals and provide ways to quantify the results using digital imaging, aiming to enhance understanding of HIV reservoirs for future cure strategies.
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Quantitative metrics on the tissue distribution of different cell phenotypes, extracellular matrix components, and signaling/cell cycle markers hold the promise for the advent of new-generation tissue-based predictive/prognostic biomarkers in clinical diagnostics. The workflow of this approach is composed of three major phases: (1) detection of multiple molecular targets on a single histologic section, (2) image acquisition, and (3) digital image processing and analysis. Here, we present the most prevalent current alternatives for step (1) and describe a three-plex staining and image acquisition platform that captures the spatial distribution of macromolecules from two different species.

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The ultrastructural quantitative aspects of peritubular capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTC). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3).

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Little is known about the morphology and clinical relevance of arteritis in renal allograft biopsies with transplant glomerulopathy. We retrospectively reviewed the morphologic findings and clinical course of 59 patients with cg, 16 of which featured concurrent arteritis (fibrosing intimal arteritis with luminal narrowing in 15, and acute intimal arteritis in 1 case). Fifteen out of the 16 cases with arteritis fulfilled the morphological diagnostic criteria for chronic active antibody-mediated rejection, and 11 cases with arteritis showed morphological evidence of concurrent, ongoing T-cell-mediated alloimmune response (acute T-cell-mediated rejection in 5, borderline changes in 6 cases).

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