Iskanje po repozitoriju

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Povzetek: Background: Since the discovery of successful direct-acting antiviral (DAA) treatment, kidneys from hepatitis C virus (HCV) RNA-positive donors represent a new opportunity to expand the organ donor pool for HCV-negative recipients. Case presentation: In this paper, we describe a unique case of transplantation of an HCV genotype 3a-infected kidney into an HCV-negative recipient who was highly sensitized, with a virtual panel-reactive antibody level of 99.96%. Prior to the kidney transplantation, the recipient received DAA treatment with glecaprevir/pibrentasvir as a viable prophylactic strategy. Post-transplant, the recipient received a triple-combination DAA regimen with glecaprevir/pibrentasvir/sofosbuvir, which continued for 12 weeks. Subsequently, viral load was undetectable at 12 and 24 weeks after treatment, with no significant adverse events associated with DAA therapy. A 12-month post-transplantation biopsy revealed mixed rejection requiring treatment. The 19-month follow-up showed a favorable outcome regarding the function of the kidney allograft and the recipient’s quality of life. HCV-positive transplantation allowed our recipient to receive a kidney from an immunologically compatible donor without donor-specific antibodies and the need for desensitization strategies. Conclusions: Each transplant center should decide on the selection of candidates for kidney transplantation from HCV RNA-positive donors to HCV-negative recipients, the availability and choice of DAA treatment, and post-transplant follow-up. Our case emphasizes the need for early DAA treatment based on viral load and HCV genotyping, as well as for careful post-transplant surveillance including protocol biopsies.
Ključne besede: kidney transplantation, HCV RNA, direct-acting antiviral (DAA), glecaprevir/pibrentasvir, sensitization, case report
Objavljeno v DiRROS: 12.11.2025; Ogledov: 166; Prenosov: 69
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Povzetek: Introduction. IgA vasculitis nephritis (IgAVN) manifests in up to 84% of adult patients with IgA vasculitis (IgAV) and is associated with an elevated risk of progression to chronic kidney failure. The underlying pathogenic mechanism of adult IgAVN in leukocytes remain largely uncharacterised. Although natural killer (NK) cells were investigated in paediatric IgAV, their specific role in the pathogenesis of adult IgAV has yet to be elucidated. Methods. RNA sequencing of leukocytes from adult IgAV patients and healthy controls (HC) was performed. NK cells’ cytotoxicity was assessed using calcein-AM stained K562 cells, and exocytosis was measured by LAMP-1/CD107a expression. Intracellular perforin and granzyme B were analyzed via flow cytometry, and cytokine secretion was measured by Luminex xMAP. Interferon-induced genes were validated with qPCR. Results. Principal component analysis (PCA) of leukocyte gene expression profiles distinguished IgAV patients from HC. Pathway enrichment analysis showed differences in patients’ subsets - Interferon signalling Reactome pathway was observed only in sample from patients with skin-limited IgAV (sl-IgAV) and was confirmed by increased expression of interferon-induced genes using qPCR. Only in samples from IgAVN patients enrichment of NK cell-mediated cytotoxicity KEGG pathway was found. NK cells from IgAVN patients showed significantly decreased cytotoxicity compared to samples from sl-IgAV patients (p = 2.53 × 10− 2). The % of CD107a+-NK cells significantly increased after stimulation in HC (p = 9.7 × 10− 3) and in sl-IgAV patient samples (p = 2.21 × 10− 2) while only a minor increase was observed in samples of IgAVN patients. IgAVN patients exhibited a decreased % of perforin+ NK cells compared to HC. Following phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation, a significant reduction in intracellular perforin level was observed in HC (p = 2.53 × 10− 2), but not in IgAVN patients NK cells. Interferon (IFN)-ϒ and macrophage inflammatory protein (MIP)-1β were significantly decreased in NK cell culture supernatants from IgAVN patients (p = 2.64 × 10− 2 and p = 2.65 × 10− 2 respectively). Conclusion. Patients with IgAVN exhibited impaired cytotoxic and immunomodulatory functions of NK cells, along with a marked absence of interferon signaling in PBMCs. Further studies are needed to confirm if discrimination of patient subsets based on leukocyte samples might be of clinical use and if deregulated NK function might contribute to the pathogenesis of nephritis in adult IgAV.
Ključne besede: immunoglobulin A, IgAVN, IgA vasculitis, RNA sequencing, kidney diseases, immunoglobulins, killer cells, adults
Objavljeno v DiRROS: 12.11.2025; Ogledov: 192; Prenosov: 77
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Povzetek: We report the case of a female patient with spinal muscular atrophy type 3c, low bone mineral density and multiple fragility fractures, successfully treated with teriparatide. She sustained a vertebral fracture at age 35 years while treatment naïve, and additionally, one vertebral fracture as well as an intertrochanteric right hip fracture during the 5-year treatment with oral bisphosphonates. A sequential 2-year treatment with teriparatide followed by a one-year treatment with oral bisphosphonate risedronate resulted in an overall 11-year fracture-free period and stable bone mineral density. Teriparatide is an osteoanabolic medication that effectively reduces vertebral and nonvertebral fractures in postmenopausal, male and glucocorticoid-induced osteoporosis, particularly in individuals at very high risk of fracture. In the context of neuromuscular disease, teriparatide proved effective in the treatment of osteoporosis in Duchenne muscular dystrophy. In contrast, the data for patients with spinal muscular atrophy are lacking. Further studies are needed to assess its role in this population.
Ključne besede: spinal muscular atrophy, osteoporosis, fracture
Objavljeno v DiRROS: 12.11.2025; Ogledov: 169; Prenosov: 72
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Ključne besede: gluten-free foods, nutritional composition, food labelling, food supply
Objavljeno v DiRROS: 12.11.2025; Ogledov: 442; Prenosov: 82
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Povzetek: Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease affecting the central nervous system with many known genetic risk factors. Although genome-wide association studies (GWAS) have identified common genetic variants with small effects associated with MS, the role of rare variants with large effects in MS aetiology remains underexplored. We hypothesized that rare variants in MS-associated genes from GWAS studies (GWAS-associated genes) are more likely to contribute to familial MS (FMS) risk than to sporadic MS (SMS). Therefore, we aimed to assess the burden of rare, predicted pathogenic (RPP) variants in GWAS-associated genes in FMS and SMS patients compared to controls. Rare genetic variants in 111 GWAS-associated genes were assessed in 87 FMS, 89 SMS and 3866 control cases. We demonstrate that RPP variants were significantly overrepresented in the FMS cohort whereas their frequency was not increased in the SMS cohort compared to controls (p-values 5.27 × 10− 74 and 1.00, respectively). Six genes (ALPK2, ANKRD55, INTS8, IQCB1, JADE2, and MALT1) significantly contributed to the burden of RPP in the FMS group. We conclude that rare variants in genes identified by GWAS might contribute to the genetic predisposition of familial MS patients.
Ključne besede: multiple sclerosis, burden analysis, whole exome sequencing (WES), rare variants, rare pathological changes, candidate genes
Objavljeno v DiRROS: 12.11.2025; Ogledov: 162; Prenosov: 68
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