Cellular immunity against cytomegalovirus and risk of infection after kidney transplantation.

Introduction: Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx.

Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management.

Background: Following kidney transplantation (KT), cytomegalovirus (CMV) infection remains an important challenge. Both prophylactic and preemptive antiviral protocols are used for CMV high-risk kidney recipients (donor seropositive/recipient seronegative; D+/R-). We performed a nationwide comparison of the 2 strategies in de novo D+/R- KT recipients accessing long-term outcomes.

Maternal cytomegalovirus infection and delayed language development in children at 3 years of age-a nested case-control study in a large population-based pregnancy cohort.

Introduction: Maternal cytomegalovirus (CMV) infection in pregnancy may result in vertical transmission of CMV to the child. Long-term effects of congenital CMV infection include visual, cognitive as well as neurological impairment. The aim of this study was to estimate the odds ratios for CMV seropositivity and seroconversion in mothers, with and without delayed language development in 3 year old children, nested within a large cohort.

Parvovirus B19 DNAemia in pregnant women in relation to perinatal death: A nested case-control study within a large population-based pregnancy cohort.

Introduction: Parvovirus B19 (B19V) is the infectious cause of exanthema infectiosum. In Europe around 40% of pregnant women are susceptible to infection. Having small children at home is the main risk factor for contracting an infection during pregnancy.

Breast cancer and cytomegalovirus.

Purpose: To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus.

Methods: We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus.

Results: Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus.

Maternal and congenital cytomegalovirus infections in a population-based pregnancy cohort study.

CMV is the most common cause of congenital infection. During the past few decades, there has been a change in behaviour that possibly has affected the CMV infection rate of mother and child. We investigated 1350 randomly selected pregnant women from the Norwegian Mother and Child Cohort Study using an algorithm for detection of maternal and congenital CMV (cCMV) infection including both serology and nucleic acid amplification assay.

High incidence of maternal parvovirus B19 infection in a large unselected population-based pregnancy cohort in Norway.

Background: Around 40% of pregnant women in Norway are parvovirus B19 (B19V) seronegative and thus at risk for B19 V infection. Studies on samples from women with symptomatic disease or known exposure have shown that nucleic acid amplification assays combined with serology increase the sensitivity and improves the diagnostic procedure.

Objectives: The aim was to investigate the seroprevalence of B19V infection, the occurrence of new infections and vertical transmission in a population-based pregnancy cohort, with special emphasis on the diagnostic methods.

Low level of MAp44, an inhibitor of the lectin complement pathway, and long-term graft and patient survival; a cohort study of 382 kidney recipients.

Background: Higher incidence of malignancy and infectious diseases in kidney transplant recipients is related to immunosuppressive treatment after transplantation and the recipient's native immune system. The complement system is an essential component of the innate immunity. The aim of the present study was to investigate the association of effector molecules of the lectin complement pathway with graft and patient survival after kidney transplantation.

Collectin Liver 1 and Collectin Kidney 1 of the Lectin Complement Pathway Are Associated With Mortality After Kidney Transplantation.

Kidney transplanted patients still have significantly higher mortality compared with the general population. The innate immune system may play an important role during periods, with suppression of the adaptive immune system. In the present study, two soluble pattern recognition molecules of the innate immune system were investigated, collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1).

Lessons Learned From a Randomized Study of Oral Valganciclovir Versus Parenteral Ganciclovir Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients: The VICTOR Trial.

The VICTOR study showed comparable efficacy of treatment with intravenous ganciclovir and oral valganciclovir for cytomegalovirus (CMV) disease in solid organ transplant recipients. Oral therapy is now recommended treatment in clinical practice and guidelines. The VICTOR biobank was used in a series of post hoc analyses that yielded unique and clinically valuable insights into CMV treatment and pathogenesis.

Polyclonal Expansion of NKG2C(+) NK Cells in TAP-Deficient Patients.

Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C(+) NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C(+) NK cell expansions. We demonstrate the expansion of NKG2C(+) NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels.

Hcmv-miR-UL22A-5p: A Biomarker in Transplantation With Broad Impact on Host Gene Expression and Potential Immunological Implications.

Cytomegalovirus (CMV) encodes multiple microRNAs. While these have been partially characterized in vitro, their relevance to clinical CMV infection has not been evaluated. We analyzed samples from a cohort of solid organ transplant patients with CMV disease (n = 245) for viral microRNA expression.

Viral infection in placenta relevant cells--a morphological and immunohistochemical cell culture study.

Viral infections in pregnancy are known to cause fetal malformation, growth restriction, and even fetal death. Macroscopic placental examination usually shows slight and unspecific changes. Histology may show secondary, non-specific tissue reaction, i.

High ficolin-3 level at the time of transplantation is an independent risk factor for graft loss in kidney transplant recipients.

Background: Recent studies have shown that activation of the complement system may be associated with long-term graft function. The aim of this retrospective study was to assess the impact of the pattern recognition molecules of the lectin pathway on long-term graft survival after kidney transplantation.

Methods: Patients transplanted in 2000 to 2001 were included.

[Allogeneic stem-cell transplantation in adults 1985-2012: results and development].

Background: Allogeneic stem cell transplantation (ASCT) has been a treatment option for patients with serious diseases of the blood and haematopoietic organs in Norway since 1985. Such treatment is potentially curative for selected patients who have a relatively short predicted survival with other treatment modalities. This article summarises the experience and results from ASCT at Oslo University Hospital Rikshospitalet.

Increased osteoprotegerin predicts poor virological outcome during anticytomegalovirus therapy in solid organ transplant recipients.

Background: Cytomegalovirus (CMV) infection involves interaction between endothelial cells and leukocyte subsets that may promote vascular inflammation and lead to treatment failure in infected individuals. Osteoprotegerin is a marker of vascular and systemic inflammation but has not been investigated in relation to treatment outcome during CMV infection.

Methods: We investigated whether circulating levels of osteoprotegerin are related to features of CMV disease and treatment outcomes during CMV infection in 291 solid organ transplant recipients receiving valganciclovir or ganciclovir in an international multicenter trial of CMV disease treatment (the VICTOR study).

The impact of early cytomegalovirus infection after kidney transplantation on long-term graft and patient survival.

This prospective observational cohort study is an extension of a previous study reporting effects of cytomegalovirus (CMV) on graft and patient survival in 471 patients who underwent kidney transplantation between 1994 and 1997. CMV pp65 antigen was measured every 7-14 d during the first three months after transplantation, given as number of CMV pp65-positive cells per 10(5) leukocytes. A positive test was defined as CMV infection.

Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9.

Patients with common variable immunodeficiency (CVID) have reduced numbers and frequencies of dendritic cells (DCs) in blood, and there is also evidence for defective activation through Toll-like receptors (TLRs). Collectively, these observations may point to a primary defect in the generation of functional DCs. Here, we measured frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in peripheral blood of 26 CVID patients and 16 healthy controls.

Secreted Wnt antagonists during eradication of cytomegalovirus infection in solid organ transplant recipients.

We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf-1 (DKK-1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK-1 and increased secreted frizzled related protein-3 levels were predictors of poor virological outcomes during follow-up.

Characterization of cytomegalovirus disease in solid organ transplant recipients by markers of inflammation in plasma.

Background: While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.

Patients And Methods: Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov NCT00431353).

Virologic suppression measured by a cytomegalovirus (CMV) DNA test calibrated to the World Health Organization international standard is predictive of CMV disease resolution in transplant recipients.

Background: Cytomegalovirus (CMV) load measurement is used to assess the efficacy of treatment of CMV disease, but lacks standardization. Using the World Health Organization (WHO) international standard for reporting, we correlated viral load with CMV disease resolution.

Methods: CMV load was quantified in plasma using a test calibrated to the WHO standard.

Treatment of cytomegalovirus disease in solid organ transplant recipients: markers of inflammation as predictors of outcome.

Background: Treatment failure or relapse is common in solid organ transplant recipients treated for cytomegalovirus (CMV) disease. Because CMV infections induce a vigorous inflammatory response, we investigated whether pretreatment levels of inflammatory markers were associated with virologic and clinical outcomes.

Methods: Solid organ transplant recipients enrolled in an international multicenter trial of CMV disease treatment (the VICTOR study) were studied (n=248).

Cytomegalovirus viremia in dried blood spots is associated with an increased risk of death in HIV-infected patients: a cohort study from rural Tanzania.

Objectives: The objectives of the study were to assess the utility of dried blood spots (DBS) for the detection of cytomegalovirus (CMV) antibody and viremia in a resource-poor setting, to study the prevalence of CMV antibody and viremia in HIV-infected patients with access to antiretroviral therapy (ART) in Tanzania, and to relate CMV viremia to outcome.

Methods: DBS were prepared from 168 ART-naïve patients at baseline. Demographic, clinical, and laboratory data were obtained from patient records.