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1.
The new occurrence of antiphospholipid syndrome in severe COVID-19 cases with pneumonia and vascular thrombosis could explain the post-COVID syndrome
Mirjana Zlatković Švenda, Melanija Rašić, Milica Ovuka, Slavica Pavlov Dolijanović, Marija Atanasković Popović, Manca Ogrič, Polona Žigon, Snežna Sodin-Šemrl, Marija Zdravković, Goran Radunović, 2025, izvirni znanstveni članek

Povzetek: Introduction: The classification of antiphospholipid syndrome (APS) comprises clinical criteria (vascular thrombosis or obstetric complications throughout life) and laboratory criteria (antiphospholipid antibodies (aPLs) positivity, confirmed at least twice at 12-week interval). Methods: In 100 patients admitted to the hospital with COVID-19 pneumonia, thrombosis and pregnancy complications were recorded during the hospital stay and in personal medical history. They were tested for nine types of aPLs at four time points (admission, deterioration, discharge, and 3-month follow-up): anticardiolipin (aCL), anti-β2-glycoproteinI (anti-β2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) isotypes IgM/IgG/IgA. Results: During hospitalization, aPLs were detected at least once in 51% of patients. All 7% of deceased patients tested negative for aPLs upon admission, and only one patient became aCL IgG positive as his condition worsened. In 83.3% of patients, intrahospital thrombosis was not related to aPLs. One patient with pulmonary artery and cerebral artery thrombosis was given an APS diagnosis (triple aPLs positivity on admission, double on follow-up). Personal anamnesis (PA) for thromboembolism was verified in 10 patients, all of whom tested negative for aPLs at admission; however, transition to aPLs positivity at discharge (as the disease subsided) was seen in 60% of patients: three of six with arterial thrombosis (at follow-up, two did not appear, and one was negativized) and three of four with deep vein thrombosis (one was confirmed at follow-up and diagnosed with APS, one was negativized, and one did not appear). At admission, the majority of the aPLs were of the aCL IgG class (58.8%). Unexpectedly, as the COVID-19 disease decreased, anti-β2GPI IgG antibodies (linked with thromboses) became newly positive at discharge (14.9%), as confirmed at follow-up (20.8%). Conclusion: The incidence of APS in our cohort was 2.0%, whereas in the general population, it ranges from 0.001% to 0.002%. The incidence might have increased even more if the four aPLs-positive patients with intrahospital thrombosis/history of thrombosis had attended follow-up. Recommendation: All patients with severe COVID-19 or post-COVID syndrome should be evaluated for current/previous thrombosis and tested for aPLs at least twice: at admission to the hospital and at discharge, then retested 3 months later in positive cases in order to be given the appropriate therapy.
Ključne besede: COVID-19, SARS-CoV2, anti-phosphatidylserine-prothrombin (aPS/PT) antibodies, anti-β2-glycoprotein I (anti-β2GPI) antibodies, anticardiolipin (aCL) antibodies, antiphospholipid antibodies (aPLs), antiphospholipid syndrome, immunology, post-COVID syndrome, vascular thrombosis
Objavljeno v DiRROS: 01.12.2025; Ogledov: 332; Prenosov: 127
.pdf Celotno besedilo (1,28 MB)
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2.
Exhausted natural killer cells in adult IgA vasculitis
Matija Bajželj, Emanuela Senjor, Nika Boštic, Matjaž Hladnik, Snežna Sodin-Šemrl, Milica Perišić, Janko Kos, Alojz Ihan, Alojzija Hočevar, Andreja Nataša Kopitar, Katja Lakota, 2025, izvirni znanstveni članek

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: 326; Prenosov: 146
.pdf Celotno besedilo (1,65 MB)
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3.
Improved protective effect of umbilical cord stem cell transplantation on cisplatin-induced kidney injury in mice pretreated with antithymocyte globulin
Željka Večerić-Haler, Andreja Erman, Anton Cerar, Helena Motaln, Katja Kološa, Tamara Lah Turnšek, Snežna Sodin-Šemrl, Katja Lakota, Katjuša Mrak Poljšak, Špela Škrajnar, Simona Kranjc Brezar, Miha Arnol, Martina Perše, 2016, izvirni znanstveni članek

Povzetek: Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone.
Ključne besede: mesenchymal stem cells, nephrotoxicity
Objavljeno v DiRROS: 25.07.2024; Ogledov: 969; Prenosov: 744
.pdf Celotno besedilo (9,54 MB)
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