Clinical utility of immune function based on IFN-γ monitoring of lymphocyte subsets for parvovirus B19 infection in renal recipients.

BACKGROUND: There should be a heightened index of suspicion for Parvovirus B19 (PVB19)-related anemia in organ transplant recipients. Thus far, there is no consensus or recommendation for clinical routine monitoring methods of PVB19 recipients to allow tailoring of immunosuppression. METHODS: We conducted a retrospective study to evaluate the utility of the function (represented by the abilities to secrete IFN-γ) and numbers of lymphocyte subsets in monitoring PVB19 infections in renal recipients posttransplant. The enrolled 109 patients were split into 2 groups according to whether the recipients had an occurrence of PVB19 infection: 37 (33.94%) recipients developed PVB19 infection and 72 (66.06%) immune-stable recipients. RESULTS: The PVB19 infected group had significantly lower absolute counts and functions of different lymphocyte subsets compared with immune-stable recipients. We showed that the frequencies of IFN-γ + CD4 + T cells, IFN-γ + CD8 + T cells, and IFN-γ + NK cells increased markedly after treatment when compared to the occurrence in patients with timepoint before therapy, especially the percentages of IFN-γ + CD4 + T cells were significantly higher. Receiver operating characteristic (ROC) analysis showed that the optimal infection indicator was IFN-γ + NK cells frequency, with an auROC curve of 0.925. Concomitantly, Cox regression analysis indicated that the post-therapy increasing level of IFN-γ secreting function was significantly predictive of recurrent infections (P < 0.001). CONCLUSIONS: We recommend prospective risk stratification for the high-risk population at risk of early-onset PVB19 infection and its recurrence involves screening strategies of immune-based surveillance with the sensitive IFN-γ + secreting monitoring for antiviral prophylaxis and preemptive therapy goal. Clinical Trial Notation: clinical trial registration number: chiCTR-ROC-17010756.

Comparison of 4 commercial enzyme immunoassays for serology testing of human parvovirus B19 infection.

BACKGROUND: Parvovirus B19 is a pathogenic virus often diagnosed by serology, yet little is known about analytical performance of commercial enzyme immunoassays (EIAs). OBJECTIVE: To investigate performance of 4 EIAs for parvovirus B19 IgM and IgG: Liaison, Euroimmun, Mikrogen and Virion/Serion. STUDY DESIGN: To compare 4 EIAs to Biotrin's ELISA on 168 samples and determine consensus score for discordant samples using Mikrogen's confirmatory line assay. RESULTS: Two thirds of results for IgM/IgG were identical for all 4 EIAs and Biotrin. Liaison shows the highest IgM sensitivity, but has low specificity. Euroimmun lacks IgM sensitivity. Mikrogen had a good overall performance, but had the lowest IgG specificity. Virion/Serion had variable performance with a low IgM specificity and the most borderline and cross-reactive results. CONCLUSIONS: Liaison and Mikrogen have similar performance to Biotrin's ELISA. Euroimmun lacks sensitivity and Virion/Serion produced many borderline and cross-reactive results.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

Flame Figures in Linear Immunoglobulin A Bullous Dermatosis Secondary to Parvovirus B19 Infection.

ABSTRACT: Flame figures represent a characteristic but nondiagnostic histological finding in eosinophilic dermatoses. Some bullous autoimmune diseases with a predominant eosinophilic infiltrate, such as bullous pemphigoid, pemphigoid gestationis, and pemphigus vegetans, may show them. However, it is rare to find them in predominant neutrophilic bullous dermatoses such as linear immunoglobulin A. We present a 60-year-old man with a history of chronic urticaria, which presented a bullous disease after an acute parvovirus B19 infection. The histological findings showed an exceptional linear immunoglobulin A bullous dermatosis with an eosinophilic infiltrate in the dermis forming "flame figures." The clinical and histopathological findings for this entity may be identical to those of other dermatoses. For this reason, combining these findings with direct immunofluorescence analysis is essential for correct diagnosis of this bullous disease.

Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.

BACKGROUND: The seroprevalence of human Parvovirus B19 (PVB19) is 70-85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. METHODS: Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017-2018. RESULTS: The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. CONCLUSION: PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.

Pure Red Cell Aplasia and Antibody-Mediated Rejection: Double Trouble in 1 Kidney Transplant Recipient Solved by Intravenous Immunoglobulin Infusion: A Case Report.

Acquired pure red cell aplasia (PRCA) is characterized by severe normocytic (rarely macrocytic) and normochromic anemia, a low reticulocytes count in peripheral blood, and near absence of erythroid precursors in the bone marrow, with a normal level of erythropoietin. We describe a case of the kidney transplant recipient, diagnosed with PRCA induced with parvovirus B19 infection. Our case demonstrates that although this complication is rare, it should be considered in a differential diagnosis of anemia diagnostics in immunocompromised patients. In our case reduced immune response resulted from post-transplant immunosuppressive therapy. In our patient, apart from infection by parvovirus B19, graft dysfunction due to polyomavirus BK virus infection was also detected together with histologic and serologic features of antibody-mediated renal graft rejection. Considering the entire clinical picture, intravenous immunoglobulin therapy (IVIg) was successfully introduced.

The seroprevalence of parvovirus B19 antibody in blood donors at the National Blood Transfusion Center in Kinshasa.

BACKGROUND: Human parvovirus B19 (PVB19) is a cosmopolitan DNA virus transmissible parenterally by blood transfusion. Therefore, the risk of transmission through asymptomatic blood donors should be considered and appropriately managed worldwide. PVB19 screening of blood and blood products for transfusion is not done routinely in the Democratic Republic of Congo (DRC). The main objective of this study was to determine the seroprevalence of PVB19 infection in healthy eligible blood donors in Kinshasa, capital of the DRC, located in the western part of the DRC, and the association of infection with the sociodemographic characteristics of blood donors. MATERIALS AND METHODS: A total of 360 whole blood donors who attended the National Center of Blood Transfusion were examined for anti-PVB19 IgG and IgM antibodies by using enzyme-linked immunosorbent assay kits. Sociodemographic information was collected on the blood donors. All statistical analyses were performed with SPSS 21. RESULTS: Among the study group, 289 men and 52 women were infected with PVB19. The mean age was 32.7 ± 9.8 years, 48.6% of donors were positive only for PVB19 IgG antibodies while 40.8% were positive for both IgG and IgM antibodies. In addition, 5.3% were positive only for PVB19 IgM antibodies and so were considered as a potential group of PVB19 transfusion-transmission. PVB19 seropositivity was significantly associated with sex, with a higher prevalence in men. In multivariate analysis, male sex and Tshangu district have emerged as major factors associated to PVB19 seropositivity. CONCLUSIONS: This research showed that recipients of blood and blood products in Kinshasa are at a high risk (5.3%) of transfusion-transmitted PVB19 infection. Therefore, the implementation of PVB19 nucleic acid testing assays capable of detecting all PVB19 genotypes and discard donations with high titer PVB19 DNA for blood products seems to be necessary.

A Meta-Analysis on the Seroprevalence of Parvovirus B19 among Patients with Sickle Cell Disease.

BACKGROUND: Parvovirus B19 (B19 V) infection had been reported to be more frequent with serious clinical outcomes in patients with sickle cell disease (SCD) than in the general population. There is a wide variation in data among the existing literature regarding the seroprevalence of B19 V in patients with SCD. These data require further summary and analyses for better accuracy. This systematic review and meta-analysis was done to estimate the seroprevalence of B19 V in patients with SCD. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, Virtual Health Library (VHL), ScienceDirect, Google Scholar, and OpenGrey were used for the systematic search. The random-effects model was used to estimate the pooled prevalence with the corresponding 95% confidence interval (CI) using OpenMeta Analyst software. Publication bias was estimated based on Begg's test, Egger's test, and examination of the funnel plot. Subgroup analyses and metaregression were used to explore the moderators of heterogeneity between studies. RESULTS: A total of 18 studies including 2890 patients were analyzed. The overall IgG seroprevalence of B19 V infection among patients with SCD was found to be 48.8% (95% CI 39.5%-58.0%). Evidence of publication bias was not detected. Evidence of acute viral infection detected by positive IgM antibodies among the screened SCD patients was found in 8.30% (95% CI 5.20%-11.4%) of them. There was a statistically significant association between seroprevalence of B19 V and geographical areas. CONCLUSION: There was a high prevalence of B19 V in patients with SCD. Healthcare providers need to be aware of the magnitude of B19 V infection in patients with SCD to ensure effective management. This review could provide a comprehensive view of B19 V prevalence in this susceptible population.

Successful re-transplantation in patient with recurrent parvovirus B19 pure red cell aplasia.

Impaired cell-mediated, as well as antibody-mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re-transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re-transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re-consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.

Oral fluid: Non-invasive alternative for parvovirus B19 diagnosis?

BACKGROUND: Infections with parvovirus B19 (B19V) have been associated with a wide range of disease manifestations of which erythema infectiosum (fifth disease) in children is most common. Clinical signs following infection of children with B19V can be similar to measles and rubella. Laboratory detection of B19V infections is based on detection of B19V-specific IgM antibodies by enzyme immunoassay (IgM-EIA) and/or B19V DNA by quantitative PCR (qPCR) on blood samples. The need for invasive sampling can be a barrier for public health diagnostics. OBJECTIVES: To evaluate the use of a dual target B19V-qPCR directed against the NS1 and VP2 of B19V on oral fluid samples as a non-invasive alternative for laboratory diagnosis of B19V infections in children below 12 years of age with exanthema. STUDY DESIGN: Oral fluid and serum samples were collected from 116 children with exanthema. All serum samples were tested by IgM-EIA/IgG-EIA, while all oral fluid and 56 serum samples were tested by B19V-qPCR. RESULTS: B19V-specific IgM antibodies were detected in 25 of 116 children in the study. B19V DNA was detected in oral fluid in 17 of the 25 children who were IgM positive, as well as two children who were IgM-equivocal or negative. The child with the equivocal IgM had a high quantity of B19V DNA in oral fluid (7 log IU/ml), compatible with an acute B19V infection. The IgM-negative child was IgG-positive and 4 log IU/ml B19V DNA was detected in the oral fluid sample, suggesting an acute infection and a falsely negative IgM. Sample size calculations indicated that oral fluid samples for qPCR should be collected from 2 to 3 children during outbreaks of exanthema to achieve similar sensitivity as IgM-EIA for one child (≥0.9) to confirm or exclude B19V. CONCLUSIONS: Results indicate that oral fluid samples are a suitable public health alternative for detection of B19V infections, potentially lowering the barriers for sampling.

Febrile Neutropenia following Parvovirus B19 Infection and Cross Anti-Kell Reaction to E. Coli in Pregnancy.

Parvovirus B19 has tropism for red line blood cells, causing immune hydrops during pregnancy. A positive anti-Kell Coombs reaction usually happens during pregnancy when there is production of antibodies that target Kell antigens, but cross reactions to other antigens may occur. A 24-year-old Gypsy primigravida, 0 Rhesus positive, presented with persistent isolated hyperthermia for 2 weeks and a positive indirect Coombs test result with anti-Kell antibodies at routine tests. She had a 19-week live fetus. The blood tests revealed bicytopenia with iron deficiency anemia, leucopoenia with neutropenia, and elevated C-reactive protein. She was medicated with imipenem, and had a slow clinical recovery. Blood, urine and sputum samples were taken to perform cultures and to exclude other systemic infections. Escherichia coli was isolated in the urine, which most probably caused a transient cross anti-Kell reaction. Haemophilus influenza in the sputum and seroconversion to parvovirus B19 was confirmed, causing unusual deficits in the white cells, culminating in febrile neutropenia. Despite the patient's lack of compliance to the medical care, both maternal and fetal/neonatal outcomes were good. This a rare case report of 2 rare phenomena, a cross anti-Kell reaction to E. coli and parvovirus B19 infection with tropism for white cells causing febrile neutropenia, both events occurring simultaneously during pregnancy.

O parvovírus B19 tem tropismo para as células sanguíneas da linha vermelha, causando hidropsia imune durante a gravidez. O teste Coombs anti-Kell positivo ocorre durante a gravidez quando há produção de anticorpos contra os antígenos de Kell, mas pode haver reações cruzadas para outros antígenos. Uma grávida primigesta de etnia cigana, de 24 anos, 0 Rhesus positivo, recorreu ao hospital às 19 semanas de gestação por hipertermia isolada persistente por 2 semanas e um teste Coombs indireto positivo por anticorpos anti-Kell em testes de rotina da gravidez. O estudo analítico revelou bicitopenia com anemia ferropênica, leucopenia com neutropenia, e elevação da proteína C-reativa. A paciente foi medicada com imipenem, e teve uma recuperação clínica lenta. Foram colhidas amostras de sangue, urina e expectoração para culturas bacterianas. Na urina, foi isolada Escherichia coli, o que provavelmente causou a reação anti-Kell cruzada transitória. Na expectoração, foi isolada Haemophilus influenza, e foi confirmada seroconversão para o parvovírus B19, que causou um déficit incomum na linhagem sanguínea branca, culminando com neutropenia febril. Apesar da má adesão aos cuidados médicos, os desfechos materno e fetal/neonatal foram bons. Este é um caso de 2 fenômenos raros, uma reação cruzada anti-Kell à infecção por E. coli, e parvovírus B19 com tropismo para células brancas causando neutropenia febril, ambos ocorrendo simultaneamente durante a gravidez.

Febrile neutropenia following parvovirus B19 infection and cross anti-kell reaction to E. coli in pregnancy / Infeção por parvovírus B19 causando neutropenia febril e reação cruzada anti-Kell com E. coli na gravidez

Abstract Parvovirus B19 has tropism for red line blood cells, causing immune hydrops during pregnancy. A positive anti-Kell Coombs reaction usually happens during pregnancy when there is production of antibodies that target Kell antigens, but cross reactions to other antigens may occur. A 24-year-old Gypsy primigravida, 0 Rhesus positive, presented with persistent isolated hyperthermia for 2 weeks and a positive indirect Coombs test result with anti-Kell antibodies at routine tests. She had a 19-week live fetus. The blood tests revealed bicytopenia with iron deficiency anemia, leucopoenia with neutropenia, and elevated C-reactive protein. She was medicated with imipenem, and had a slow clinical recovery. Blood, urine and sputum samples were taken to perform cultures and to exclude other systemic infections. Escherichia coli was isolated in the urine, which most probably caused a transient cross anti-Kell reaction. Haemophilus influenza in the sputum and seroconversion to parvovirus B19 was confirmed, causing unusual deficits in the white cells, culminating in febrile neutropenia. Despite the patient's lack of compliance to the medical care, both maternal and fetal/neonatal outcomes were good. This a rare case report of 2 rare phenomena, a cross anti-Kell reaction to E. coli and parvovirus B19 infection with tropism for white cells causing febrile neutropenia, both events occurring simultaneously during pregnancy.

Resumo O parvovírus B19 tem tropismo para as células sanguíneas da linha vermelha, causando hidropsia imune durante a gravidez. O teste Coombs anti-Kell positivo ocorre durante a gravidez quando há produção de anticorpos contra os antígenos de Kell, mas pode haver reações cruzadas para outros antígenos. Uma grávida primigesta de etnia cigana, de 24 anos, 0 Rhesus positivo, recorreu ao hospital às 19 semanas de gestação por hipertermia isolada persistente por 2 semanas e umteste Coombs indireto positivo por anticorpos anti-Kell em testes de rotina da gravidez. O estudo analítico revelou bicitopenia com anemia ferropênica, leucopenia com neutropenia, e elevação da proteína C-reativa. A paciente foi medicada com imipenem, e teve uma recuperação clínica lenta. Foram colhidas amostras de sangue, urina e expectoração para culturas bacterianas. Na urina, foi isolada Escherichia coli, o que provavelmente causou a reação anti-Kell cruzada transitória. Na expectoração, foi isolada Haemophilus influenza, e foi confirmada seroconversão para o parvovírus B19, que causou um déficit incomum na linhagem sanguínea branca, culminando com neutropenia febril. Apesar da má adesão aos cuidados médicos, os desfechos materno e fetal/neonatal foram bons. Este é um caso de 2 fenômenos raros, uma reação cruzada anti-Kell à infecção por E. coli, e parvovírus B19 comtropismo para células brancas causando neutropenia febril, ambos ocorrendo simultaneamente durante a gravidez.

Immunohistochemical Demonstration of Parvovirus B19 Viral Protein 2 in Periflexural Exanthema in an Adult, Supporting Antibody-Dependent Enhancement as Means of Endothelial Uptake of the Virus.

Human parvovirus B19 (B19V) causes a number of skin exanthemas and has been related to both cutaneous and systemic diseases. Tropism of the virus for the rapidly proliferating erythroid progenitor cells in the bone marrow and fetal liver explains the pathogenesis of anemia and fetal hydrops. The cutaneous lesions of erythema infectiosum and other B19V-related exanthemas have been attributed to the deposition of immune complexes in the skin. We report on the immunohistochemical detection of B19V protein in the cytoplasm of dermal endothelial cells in a case of periflexural exanthema in a 28-year-old woman. An antibody-dependent enhancement mechanism of entry has been suggested for B19V in myocardial endothelial cells and could also be involved in B19V-related exanthemas.

[Virus-associated arthritis]. / Virusassoziierte Arthritiden.

Epidemiological studies suggest a viral etiology in approximately 1% of patients presenting with acute arthritis. The arthritogenic effect of viral infections may be related to viral invasion of synovial cells, the cellular and humoral immune response to viral antigens or by induction of autoimmunity. Viral arthritis can mimic rheumatoid arthritis by presenting as a symmetrical polyarticular disease often accompanied by a rash and influenza-like symptoms. Serological testing for pathogen-specific IgM and IgG antibodies is frequently performed for establishing a viral etiology of arthritis. Virus isolation from the joints or detection of viral nucleic acids in the synovium or synovial fluid is only rarely successful and does not always provide proof of a viral origin of arthritis. While viral arthritis in most cases is self-limiting, protracted disease can occur.

Parvovirus B19 infection associated with hemolytic anemia and cranial polyneuropathy.

Parvovirus B19 (PB19) is a common, widespread, small, single-stranded DNA virus which has been linked with a broad spectrum of clinical illnesses, including a variety of neurological complications such as encephalitis, meningitis, myelitis, stroke, cerebellar ataxia, and neuropathy. The authors describe a case of PB19 infection associated with hemolytic anemia and cranial polyneuropathy involving the second and third cranial nerves in a 23-year-old immunocompetent woman. The diagnosis of acute PB19 infection was established with detection of positive DNA and anti-PB19 IgM antibodies in blood samples. Antiganglioside antibody studies were performed and serum anti-GD1b IgG was strongly positive. Further investigation was normal or negative, excluding other infectious or autoimmune disorders. The patient was initially treated with a 5-day course of intravenous immunoglobulin (IGIV). Because of incomplete neurological recovery, methylprednisolone was also administered 7 days after IGIV therapy initiation. Complete resolution of clinical symptoms was observed 3 months after disease onset at follow-up visit, despite the persistence of PB19 DNA and anti-PB19 IgM antibodies in serum 5 months after the initial presentation. Our report provides evidence that PB19 could affect both the central and peripheral nervous system, possibly by triggering an autoimmune mechanism that leads to autoantibody production.