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Background/Aims: Acute liver injury is a common manifestation of parvovirus B19 (PVB19) infection in immunocompromised patients. However, literature in immunocompetent children is scarce. We aimed to study the clinicolaboratory features and outcome of hepatic involvement by PVB19 infection in hospitalized children. Methods: We retrospectively analyzed our prospectively kept database of all children (<18 years old) admitted with acute viral hepatitis (AVH), acute liver failure (ALF) or acute-on-chronic liver failure (ACLF), and PVB19 infection between January 2010 and December 2023. Clinical features, laboratory parameters, and complications were evaluated. Poor outcome was defined as death or liver transplantation. Results: A total of 35 children (19 boys [54%], median age: 7.25 [interquartile range: 4-10.8] years) with PVB19-related hepatitis were studied (28 [80%] isolated PVB19 infection and 7 [20%] coinfections [3 with Epstein-Barr virus, 2 with hepatitis A, and 1 each with hepatitis-E and cytomegalovirus]). AVH (17, 49%) was the most common presentation, followed by ALF (13, 37%) and acute insult in ACLF (5, 14%). Patients with coinfection had significantly higher bilirubin (14.6 [9.4-21.5] vs 6.8 [4.3-10.9] mg/dl; P=0.004) and transaminases (ALT: 697 [428-1296] vs. 277 [157-478] U/L; P=0.02) but similar mortality (1/7 vs 6/23; P=1.0) than PVB19 alone. Nine cases (25.7%) had extrahepatic complications (hemophagocytic lymphohistiocytosis [HLH]: 3, acute kidney injury: 3, aplastic anemia: 2, and myocarditis: 1). Poor outcome occurred in 38% (5/13) ALF, 11.7% (2/17) AVH (HLH: 1, myocarditis: 1), and none (0/5) of the ACLF cases. Conclusion: PVB19 should be considered in children presenting with indeterminate acute liver injury, especially in younger children or those with complications such as aplastic anemia, HLH, or myocarditis.
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There has been a surge in the interest to utilize plants as hosts for producing vaccine antigens. In this study, we demonstrated the successful expression of the human parvovirus B19 (B19V) capsid protein (VP2) in Nicotiana benthamiana cells. The B19V VP1 and VP2 genes were cloned under the control of estrogen-inducible promoters and transiently expressed in N. benthamiana leaves using the agroinfiltration method. The addition of estrogen significantly boosted the expression of VP2. Furthermore, codon optimization of the VP2 sequence resulted in over a 30-fold increase in its expression compared with that of the wild-type. Analysis of negatively stained samples by sucrose density gradient ultracentrifugation and electron microscopy revealed that the expressed VP2 proteins formed spherical particles with diameters of approximately 20 nm. Immunostaining analysis of protoplasts derived from VP2-expressing N. benthamiana leaves indicated that VP2 signals were predominantly localized in the cytoplasm. These findings strongly suggested that B19V VP2 assembles and formed virus-like particles (VLPs) within the cytoplasm of N. benthamiana cells, presenting a promising method for producing B19V VLPs in plant systems.
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BACKGROUND: Parvovirus B19 (B19 V) infection during pregnancy can cause adverse fetal outcomes. Our aim was to characterize both clinical and asymptomatic maternal and neonatal cases by studying virological and serological markers of B19 V infection, and to sequence the complete genome of the circulating virus in Argentina. METHODS: Symptomatic patients were included based on maternal and/or fetal-neonatal signs attributable to B19 V infection during gestation. Pregnant patients were analyzed in either the timely diagnosis group (TD, samples obtained when symptoms were present and infection was suspected) or the retrospective diagnosis group (RD, samples collected immediately postpartum), and newborns were analyzed at birth. A sample of asymptomatic individuals was also analyzed. Diagnostic tests (PCR/qPCR/serology) and sequencing were performed on archived serum samples from 2018 to 2023, and clinical data were obtained from medical records. RESULTS: We studied 328 symptomatic patients, including 185 pregnant patients (73 TD and 112 RD) and 143 newborns. Among them, we identified 27/328 (8.2 %) positive cases (B19V+): 12/73 (16.4 %) in the TD group, 6/112 (5.4 %) in the RD group, and 9/143 (6.3 %) newborns. Within the 77 mother-newborn pairs included, there were 8 (10.4 %) B19 V infections and 6 cases of vertical transmission. Additionally, B19 V infection was detected in 26/310 (8.4 %) asymptomatic patients. Phylogenetic analysis identified genotype 1a as a circulating strain in Argentina. CONCLUSIONS: Our findings highlight the need to raise awareness and enhance diagnostic approaches in Argentina to more effectively identify and manage B19 V infections during pregnancy in our region.
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BACKGROUND: Since the beginning of 2024, several European countries reported unusually high numbers of Human parvovirus B19 (B19V) infections. An increase in B19V incidence rate might have implications for blood products for direct transfusion, however, large data sets for analysis of this outbreak are missing. STUDY DESIGN AND METHODS: B19V nucleic acid testing (NAT) of plasma donations collected between June 2018 and May 2024 from mainly Central European countries (n = 9.6 million) and the United States (n = 70.7 million) was done to the individual donation level. RESULTS: In Central Europe, there was a marked increase in B19V incidence from November 2023 onwards, which peaked in April 2024 with a 33-fold higher than average B19V incidence versus before the COVID-19 pandemic. In the United States, a similar trend was seen, with a yet still 6-fold lower increase than in Europe at the same time. The largest increase in B19V positivity was seen in the youngest plasma donor cohort. DISCUSSION: A B19V infection gap during the COVID-19 pandemic is likely the basis for the rebound outbreak in 2023/2024, particularly in Europe. B19V NAT of millions of plasma donations provides for large scale numbers to solidify available epidemiology insight, and to support adequate risk assessments. Based on the situation it may be prudent to consider B19V NAT for blood components specifically directed towards transfusion to higher risk recipients, or alternatively, preselecting B19V seropositive individuals or advanced age donors at higher likelihood of seropositivity and thus lower risk of virus transmission.
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Angioimmunoblastic T-cell lymphoma (AITL) is a rare and challenging subtype of T-cell lymphoma often presenting with skin rashes and difficult diagnostic features. Its presentation can mimic other conditions, complicating accurate diagnosis. This case shows AITL in a 74-year-old man initially presenting with anemia that mimicked pure red cell anemia caused by parvovirus B19. The patient exhibited direct Coombs-positive anemia and recurrent urticarial-like rashes, which were initially misleading. This case emphasizes the critical need for considering lymphoma in patients presenting with direct Coombs-positive anemia and recurrent urticarial-like rashes It underscores the importance of revisiting and thoroughly assessing medical histories to enable accurate diagnosis, even when initial presentations suggest alternative diagnoses. Early recognition and appropriate management of AITL are crucial for improving patient outcomes.
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Parvovirus B19, commonly associated with erythema infectiosum in children, can also present with various clinical manifestations in adults, including arthropathy, myocarditis, vasculitis, and neurological complications. This case report describes a 39-year-old male who presented with fever, rash, and polyarthralgia, followed by the sudden onset of left-sided facial weakness and slurred speech. Clinical examination revealed lower motor neuron facial nerve palsy and signs consistent with cutaneous small-vessel vasculitis. Extensive laboratory investigations confirmed the presence of parvovirus B19 DNA, while tests for other common viral infections and autoimmune markers were negative. The patient was treated with oral prednisolone, resulting in significant improvement in his symptoms over the course of one month. This case highlights the rare but important association between parvovirus B19 infection and both neurological and dermatological manifestations. It underscores the need for healthcare providers to consider viral etiologies in the differential diagnosis of facial nerve palsy and vasculitis, particularly when presented with concurrent symptoms of systemic infection. Early diagnosis and appropriate management are crucial for improving patient outcomes in such atypical presentations. This report adds to the growing body of literature on the diverse clinical manifestations of parvovirus B19, emphasizing the importance of recognizing and treating these rare complications promptly.
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Non-immune hydrops fetalis represents a diagnostic challenge in high-risk pregnant women. Vertical infection with human parvovirus B19 (B19V) is a possible cause. National guidelines propose maternal serologic screening (IgG/IgM), which may be insufficient in some situations. We report a case of vertical B19V infection with difficulties in prenatal diagnosis. Preterm newborn, normal weight (2950 g), born to a 30-year-old mother with anemia and hydrops fetalis (week 17). Cardiac, chromosomal, isoimmunization-Rh, and usual infectious causes (TORCH) were ruled out. Maternal serology for B19V showed IgG+ and IgM-, and the diagnosis was dismissed. The newborn presented abdominal distension (ascites), anemia, and jaundice. Postnatal results confirmed the diagnosis with DNA+ for B19V. Discharge at 17 days with good evolution. The protocol for B19V screening in vertical infection needs to be revised by incorporating early molecular studies (PCR) from the early stages of gestation to optimize the diagnosis and treatment of patients with this congenital infection.
La hidropesía fetal no inmune representa un desafío diagnóstico en embarazadas de alto riesgo. La infección vertical por parvovirus humano B19 (B19V) es una causa posible. Las guías nacionales proponen pesquisas serológicas maternas (IgG/IgM) que pueden ser insuficientes en algunas situaciones. Se reporta un caso de infección vertical por B19V con dificultades en el diagnóstico prenatal. Recién nacido prematuro, peso adecuado (2950 g). Hijo de madre de 30 años, con anemia e hidropesía fetal (semana 17). Se descartaron causas cardíacas, cromosómicas, isoinmunización-Rh e infecciosas habituales (TORCH). Serología materna para B19V mostró IgG+ e IgM- desestimando el diagnóstico. El neonato presentó distensión abdominal (ascitis), anemia e ictericia. Resultados posnatales confirmaron diagnóstico con ADN+ para B19V. Alta a los 17 días con buena evolución. El protocolo de pesquisa de B19V en infección vertical requiere ser revisado incorporando precozmente estudios moleculares (PCR) desde etapas tempranas de la gestación, y así optimizar el diagnóstico y tratamiento de los pacientes con esta infección congénita.
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Ensuring the safety of blood and blood products is a vital aspect of healthcare. The potential for transmission of pathogens through blood and blood products makes transfusion safety a significant concern. Despite advancements in testing methodologies, donated blood products still pose a risk for infection transmission. Human parvovirus B19 (B19V) is a small, single-stranded, non-enveloped DNA virus transmissible parenterally by blood transfusion. B19V causes a wide range of clinical manifestations, which is generally harmless in healthy individuals. B19V infection may cause severe complications, such as aplastic crises, as it affects erythrocyte progenitor cells in individuals with increased erythrocyte turnover. Additionally, B19V can be transmitted from pregnant women to their foetus, potentially causing hydrops fetalis and foetal death. The potential for transmission through blood and blood products makes B19V a significant concern for transfusion safety. In response to the growing recognition of B19V's impact on transfusion safety, various international health organisations have introduced guidelines to minimise its transmission through blood and plasma products. However, the implementation of these guidelines varies globally, with some regions, such as India, still lacking formal protocols for B19V monitoring. This review article explores the existing methodologies for screening blood donors for B19V, assesses the associated transfusion risks, and considers the implications for public health and clinical practice. By emphasising advancements in diagnostic techniques and the challenges of their implementation, this article provides a comprehensive overview of efforts to reduce the transmission of B19V through blood transfusions, thereby ensuring safer blood supplies and improved patient outcomes.
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Despite scarcity of data, in recent years, human parvovirus B19 (PVB19) has been emerging as an important pathogen in acute encephalitis syndrome (AES). But, PVB19 virus is mostly looked for only after the exclusion of other common pathogens implicated in AES. Hence, this study was conducted to correlate clinical, radiological, and sequencing data to establish the crucial role of PVB19 in AES. Cerebrospinal fluid and/or serum samples were collected from AES patients as per WHO criteria and tested by ELISA, real-time PCR and bacterial culture sensitivity for various pathogens. PVB19 positive samples were subjected to sequencing. PVB19 attributed to 5% of total AES cases in the present study with fatalities in two of eight cases. Two isolates of PVB19 belonged to Genotype 1 A whereas one belonged to Genotype 3B. On multivariate analysis of predictive symptoms of PVB19 AES cases, blurring of vision (odds ratio [OR] 20.67; p = 0.001) was found to be significant independent predictor of PVB19 AES. Six of eight patients (two encephalitis specific and four nonspecific) had abnormal radiological findings. Hence, being an emerging viral pathogen, PVB19 should be included in the diagnostic algorithm of AES for prompt diagnosis and definitive management to prevent undesired neurological sequelae.
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Infecções por Parvoviridae , Parvovirus B19 Humano , Humanos , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/isolamento & purificação , Masculino , Feminino , Infecções por Parvoviridae/virologia , Infecções por Parvoviridae/complicações , Criança , Adolescente , Adulto Jovem , Pré-Escolar , Genótipo , Adulto , Encefalopatia Aguda Febril/virologia , Análise de Sequência de DNA , DNA Viral/líquido cefalorraquidiano , DNA Viral/genética , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática , Encefalite Viral/virologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Background: Rabies in Turkey is maintained by dogs, but following a sustained spill-over, red fox mediated rabies had spread from the Aegean region to the central part of Türkiye. During the past four years from 2019 to 2023 large scale efforts used oral rabies vaccination (ORV) to control rabies in red foxes. Here, we present the results of the largest ORV campaign on the Asian continent. Methods: ORV campaigns were carried out twice a year in spring and autumn with a targeted bait density of 20-23 baits/km2. Monitoring of ORV campaigns included the GIS-based analyses of bait distribution, the assessment of bait uptake through biomarker detection and the determination of seroconversion (sero-positivity in ELISA) in the target species collected within the vaccination area. For determination of fox rabies incidence in vaccination areas as the main indicator of the performance of the ORV campaigns, epidemiological data was obtained from the national passive surveillance program. Results: Aerial bait distribution was highly accurate, with >99 % of baits being recorded from targeted zones, thus meeting the desired bait densities. Although the overall bait uptake (28.1 %; 95 %CI: 23.2-32.8) and seroprevalance (36.3 %; 95 %CI: 30.0-43.2) were low, rabies incidence drastically decreased in ORV areas and rabies was eliminated from western and central parts of Turkey, with no reported cases in foxes from ORV areas in 2022 and 2023. Conclusions: A large-scale ORV campaign against fox rabies using high quality vaccine baits and the GIS-aided and monitored bait distribution was able to control fox mediated rabies in the western and central parts of Türkiye. Rabies control both in dogs and foxes should be expanded to cover also the eastern parts of Türkiye, to become eventually rabies free.
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A core component of every blood program is the supply of safe blood and blood products. The elevated risk of transmission through these products is due to parvovirus B19 (B19V) resistance to the virus inactivation procedures. Our study aimed to screen asymptomatic blood donors for B19V at a tertiary care hospital in Chennai, Tamil Nadu, between September 2020 and June 2021. Sera from 106 healthy blood donors who tested negative for Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV), syphilis, and malaria were tested for anti-B19V IgM and IgG using a qualitative indirect enzyme-linked immunosorbent assay (ELISA). In the study population, 23.5% (n = 25) of donors tested IgM positive, 38.6% (n = 41) tested IgG positive, and 7.5% (n = 8) tested positive for both IgM and IgG. A proportion of 61.3% (n = 65) of the blood donors tested IgG negative, suggesting they had no past B19V infection. B19V DNA was not detected in any of the subjects. The high seroprevalence of IgM indicates that blood donors may have been recently exposed to B19V, potentially posing a risk to immunocompromised individuals and those with hematological stress. Further longitudinal studies with a larger sample size are recommended to better understand the risk of B19V transfusion transmission.
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Anticorpos Antivirais , Doadores de Sangue , Imunoglobulina G , Imunoglobulina M , Parvovirus B19 Humano , Humanos , Índia/epidemiologia , Parvovirus B19 Humano/imunologia , Masculino , Adulto , Feminino , Anticorpos Antivirais/sangue , Imunoglobulina M/sangue , Imunoglobulina G/sangue , Estudos Soroepidemiológicos , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/imunologia , Pessoa de Meia-Idade , Adulto Jovem , AdolescenteRESUMO
Aortitis and mycotic aneurysm are vascular conditions characterized by inflammation of the aortic wall or the presence of an aneurysm resulting from microbial infection. This is a rare case of aortic aneurysm caused by atherosclerosis, with Streptococcus constellatus and Parvovirus B19 infection, in a 60-year-old male. The patient presented with rigors and pleuritic chest pain, and was found to have a saccular aneurysm of the ascending aorta and pericardial effusion. The patient underwent urgent replacement of the ascending aorta and completed 6 weeks of antibiotics with good recovery. This case emphasizes the importance of considering rare organisms in patients with aortitis and mycotic aneurysm, particularly in cases with blood cultures without microbial growth. Early diagnosis and treatment may be essential for the prevention of life-threatening complications.
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Despite Parvovirus B19 (B19V) generally causing mild or asymptomatic infections, and only certain high-risk groups such as hematological or immunocompromised patients and pregnant women tending to develop complications, several factors challenge the assumption of a "benign" clinical course in immunocompetent adults and adolescents. A significant proportion of the population may harbor undiagnosed health conditions or genetic predispositions that could render them more susceptible to severe B19V complications. These could include mild hematological disorders, immune dysregulation not resulting in overt immunodeficiency, or underlying cardiac conditions. Concurrent infections with other pathogens, even seemingly minor ones, could synergistically increase the severity of B19V infection, leading to more pronounced clinical manifestations. While not definitively proven, the possibility of emerging B19V strains with increased virulence or altered tissue tropism cannot be entirely discounted. Additionally, the period of pandemic-related restrictions likely led to reduced B19V circulation, potentially resulting in a cohort of young adults with limited natural immunity, making them more vulnerable to infection. Potential clinical consequences include atypical and severe presentations, even in individuals without known risk factors. The traditional focus on B19V primarily as a pediatric concern might lead to underdiagnosis or delayed diagnosis in adults, potentially hindering timely intervention and management. A surge in B19V-related complications, even if individually mild, could collectively strain healthcare resources, particularly in settings with limited capacity or pre-existing pressures. Possible recommendations are to heighten clinical awareness with a high index of suspicion for B19V infection in adults and adolescents presenting with compatible symptoms, even in the absence of classic risk factors. Additionally, expanding testing criteria and enhancing public health surveillance efforts would be prudent.
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Infecções por Parvoviridae , Parvovirus B19 Humano , Humanos , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/imunologia , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/virologia , Fatores de Risco , Imunocompetência , Feminino , Adulto , Gravidez , Adolescente , Hospedeiro ImunocomprometidoRESUMO
Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.
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Parvovirus B19 is a virus that causes a common and usually harmless infection in both children and adults. If the virus is transmitted transplacentally during pregnancy, it can have serious consequences for both the pregnant woman and the fetus. Potential complications include severe fetal anemia, which can lead to intrauterine fetal death. A common ultrasound finding in fetuses affected by parvovirus B19 is fetal edema, which is associated with a poor prognosis. Additionally, a rare but serious complication in pregnant women with parvovirus B19 infection is mirror syndrome. The diagnosis of parvovirus B19 infection during pregnancy necessitates close monitoring of the fetal condition. If fetal anemia is suspected, intrauterine transfusion is indicated to increase fetal survival. This study presents eight cases of parvovirus B19 infection in pregnant women, highlighting the various maternal-fetal complications encountered, along with diagnostic and treatment strategies.
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OBJECTIVE: Our objective was to correlate parvovirus-B19 and Epstein-Barr virus (EBV) infections with apoptotic biomarker levels in tissues from placentas from spontaneous abortions and cases of elective termination of pregnancy. We also explored if viral presence could cause spontaneous abortions by trying to associate the levels of pro-apoptotic markers with adverse pregnancy outcomes. MATERIALS AND METHODS: We used 194 placental samples, of which 152 came from spontaneous abortions and were the study group and 42 controls came from cases of elective pregnancy termination. Hematoxylin and eosin (H&E) staining was performed to investigate morphological changes in the tissues, and then indirect immunohistochemistry to evaluate the expression of B19, EBV, M30, terminal deoxynucleotidyl transferase assay (TUNEL), and nuclear factor kappa B (NF-kB). Statistical analysis was performed using SPSS v. 19.0 (IBM). RESULTS: Higher levels of apoptosis were observed in the spontaneous abortion group (p<0.001) with statistical significance and their presence was also correlated with statistical significance with viral infection (p<0.001). Also, viral infections were observed only in cases of spontaneous abortion. When simple and multivariate logistic regression was performed we confirmed that viral presence remained an independent prognostic factor for high expression of all apoptotic biomarkers with statistical significance (p<0.001). CONCLUSIONS: Our results indicate that viral presence can lead to deregulation of apoptotic pathways within the maternal-fetal environment and thus work as a trigger event for spontaneous abortions.
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One of the issues during the post-transplant phase is anemia. The increased risk of graft rejection makes evaluating transplant recipients difficult. Parvovirus-B19 (PV-B19) should be considered one of the differential diagnosis of post-transplant anemia (PTA) in renal transplantation recipients. In this article, we report a 32 year old man who was admitted to the hospital with anemia. During the assessment, infection with PV-B19 was confirmed as the cause of the anemia. He received intravenous immunoglobin (IVIG) as the treatment.
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Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.
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Armadilhas Extracelulares , Neutrófilos , Parvovirus B19 Humano , Trombose , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Humanos , Animais , Camundongos , Parvovirus B19 Humano/imunologia , Trombose/virologia , Trombose/patologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/metabolismo , Células HL-60 , Espécies Reativas de Oxigênio/metabolismo , Modelos Animais de Doenças , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/virologia , Imunoglobulina G/imunologia , MasculinoRESUMO
BACKGROUND: This study aims to explore the molecular mechanism of lncRNA RP3-340B19.3 on breast cancer cell proliferation and metastasis and clinical significance of lncRNA RP3-340B19.3 for breast cancer. METHODS: The subcellular localization of lncRNA RP3-340B19.3 was identified using RNA fluorescence in situ hybridization (FISH). The expression of lncRNA RP3-340B19.3 in breast cancer cells, breast cancer tissues, as well as the serum and serum exosomes of breast cancer patients, was measured through quantitative RT-PCR. In the in vitro setting, we conducted experiments to observe the effects of RP3-340B19.3 on both cell migration and proliferation. This was achieved through the utilization of transwell migration assays as well as clone formation assays. Meanwhile, transwell migration assays and clone formation assays were used to observe the effects of MDA-MB-231-exosomes enriched in RP3-340B19.3 on breast cancer microenvironment cells MCF7 and BMMSCs. Additionally, western blotting techniques were used to assess the expression levels of proteins associated with essential cellular processes such as proliferation, apoptosis, and metastasis. In vivo, the impact of RP3-340B19.3 knockdown on tumour weight and volume was observed within a nude mice model. We aimed to delve into the intricate molecular mechanisms involving RP3-340B19.3 by using bioinformatics analysis, dual luciferase reporter gene experiments and western blotting. Moreover, the potential correlations between RP3-340B19.3 expression and various clinical pathological characteristics were analyzed. RESULTS: Our investigation revealed that RP3-340B19.3 was expressed in both the cytoplasm and nucleus, with a noteworthy increase in breast cancer cells. Notably, we found that RP3-340B19.3 exerted a promoting influence on the proliferation and migration of breast cancer cells, both in vitro and in vivo. MDA-MB-231-exosomes enriched in RP3-340B19.3 promoted the proliferation and migration of MCF7 and BMMSCs in vitro. Mechanistically, RP3-340B19.3 demonstrated the capability to modulate the expression of MORC4 by forming a complex with miR-4510. This interaction subsequently triggered the activation of the NF-κB and Wnt-ß-catenin signaling pathways. Furthermore, our study highlighted the potential diagnostic utility of RP3-340B19.3. We discovered its presence in the serum and exosomes of breast cancer patients, showing promising efficacy as a diagnostic marker. Notably, the diagnostic potential of RP3-340B19.3 was particularly significant in relation to distinguishing between different pathological types of breast cancer and correlating with tumour diameter. CONCLUSION: Our findings establish that RP3-340B19.3 plays a pivotal role in driving the proliferation and metastasis of breast cancer. Additionally, exosomes enriched in RP3-340B19.3 could influence MCF7 and BMMSCs in tumour microenvironment, promoting the progression of breast cancer. This discovery positions RP3-340B19.3 as a prospective novel candidate for a tumour marker, offering substantial potential in the realms of breast cancer diagnosis and treatment strategies.
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Background: Parvoviruses, characterized by their tropism for blood cells, can manifest as asymptomatic infections. With their ability to persist in blood, assessing the prevalence of Parvovirus B19 (B19V) and Parvovirus 4 (PARV4) among healthy blood donors is essential for evaluating the potential transmission risks through blood transfusions, emphasizing the need for comprehensive screening protocols. Methods: Four hundred blood donors participated in the study, with their blood specimens subjected to Real-Time PCR analysis for B19V and PARV4 nucleic acids after obtaining informed consent. Additionally, Complete Blood Count (CBC) assessments and determination of anti-B19 V-IgM and anti-B19 V-IgG antibody titers were performed using Enzyme-Linked Immunosorbent Assay (ELISA) for all collected samples. Results: The results reveal that 12 out of 400 individuals (3 %) exhibited positive results for B19V DNA, while 6 out of 400 individuals (1.5 %) tested positive for PARV4 DNA. Additionally, 8 out of 400 individuals (2 %) displayed positive results for anti-B19V IgM, and 306 out of 400 individuals (76.5 %) exhibited positive results for anti-B19 IgG. Notably, one donation from a donor presenting anti-IgM antibodies was subsequently confirmed as B19V DNA-positive through Real-Time PCR. In the analysis of CBC, a significant disparity in platelet levels was observed between B19V-positive donors, PARV4-positive donors, and B19V-negative donors. Conclusions: The study suggests that individuals at high risk, lacking detectable B19V antibodies, should undergo systematic screening and exclusion. This precaution is intended to minimize potential contamination risks within the studied cohort, despite the undefined pathogenesis and clinical implications of PARV4.