Prevalence of Polyomavirus BK and JC Infection and Replication in 400 Healthy Blood Donors

BackgroundThe replication of BK virus (BKV) and JC virus (JCV) is linked to polyomavirus-associated nephropathy, hemorrhagic cystitis, and multifocal leukoencephalopathy in immunodeficient patients, but the behavior of these viruses in immunocompetent individuals has hardly been characterized MethodsWe used EIA to study samples obtained from 400 healthy blood donors aged 20-59 years for BKV- and JCV-specific antibodies against virus-like particles. We also studied BKV and JCV loads in plasma and urine among these individuals by use of real-time polymerase chain reaction ResultsIgG seroprevalence was 82% (328 of 400 donors) for BKV and 58% (231 of 400) for JCV. As age increased (age groups were divided by decade), the seroprevalence of BKV decreased from 87% (87 of 100) in the youngest group (aged 20-29 years) to 71% (71 of 100) in the oldest group (aged 50-59 years) (P=.006), whereas the seroprevalence of JCV increased from 50% (50 of 100) in the youngest group to 68% (68 of 100) in the oldest group (P=.06). Asymptomatic urinary shedding of BKV and JCV was observed in 28 (7%) and 75 (19%) of 400 subjects, respectively, with median viral loads of 3.51 and 4.64 log copies/mL, respectively (P<.001). Unlike urinary BKV loads, urinary JCV loads were positively correlated with IgG levels. The shedding of JCV was more commonly observed among individuals who were seropositive only for JCV, compared with individuals who were seropositive for both BKV and JCV, suggesting limited cross-protection from BKV immunity. Noncoding control regions were of archetype architecture in all cases, except for 1 rearranged JCV variant. Neither BKV nor JCV DNA was detected in plasma ConclusionsOur study provides important data about polyomavirus infection and replication in healthy, immunocompetent individuals. These data indicate significant differences between BKV and JCV with respect to virus-host interaction and epidemiolog

Quantity of HLA-C surface expression and licensing of KIR2DL+ natural killer cells

Natural killer (NK) cells require interaction of inhibitory surface receptors with human leukocyte antigen (HLA) ligands during development to acquire functional competence in a process termed "licensing.” The quantity of HLA required for this process is unknown. Two polymorphisms affecting HLA-C surface expression (rs9264942 and rs67384697) have recently been identified, and shown to influence progression of HIV infection. We typed a cohort of healthy donors for the two HLA-C-related polymorphisms, KIR2DL1 and KIR2DL3, and their respective HLA-C ligands and analyzed how HLA ligands influenced licensing status of killer cell immunoglobulin-like receptor (KIR)+ NK cells in terms of degranulation and cytokine production in response to HLA-deficient target cells. The presence of respective HLA class I ligands increased the function of KIR2DL1+ and KIR2DL3+ NK cells in a dose-dependent manner. In contrast, neither of the HLA-C-related polymorphisms nor the quantity of cell surface HLA-C had any significant effect on NK cell function. Interestingly, HLA-Cw7—an HLA-C allele with low surface expression—licensed KIR2DL3+ NK cells more strongly than any other KIR2DL3 ligand. The quantity of cell surface HLA-C does not appear to influence licensing of NK cells, and the HLA-C-related polymorphisms presumably influence HIV progression through factors unrelated to NK cell educatio

ABO blood group-incompatible living donor kidney transplantation: a prospective, single-centre analysis including serial protocol biopsies

Background. ABO incompatible kidney transplantation using antigen-specific immunoadsorption is increasingly performed but data on outcome, complications and protocol biopsies are still scarce. The present prospective single-centre study was aimed at these issues. Methods. This was a prospective single-centre cohort study of 10 successive ABO incompatible living donor kidney transplantations at the University Hospital Basel from September 2005 to October 2007. The following parameters were closely monitored during the whole follow-up: graft function, albuminuria, blood group antibody titres, CD19+ cell count, total IgG and IgG subclasses, CMV antigenaemia, decoy cells in the urine, EBV and polyoma BK virus PCR in the blood. Protocol biopsies were performed on Days 0 and 7 after 3, 6, 12 and 18 months. Results. Patient and graft survival is 100% after a median follow-up of 489 days (range 183-916 days). Median serum creatinine is 137 μmol/l (range 70-215 μmol/l), and median urine albumin-creatinine ratio (UACR) is 3.1 mg/ mmol (range 0.6-7.8 mg/mmol) at the time of the last follow-up. All patients had sustained diminished CD19+ cell count and/or total IgG concentrations. Neither CMV antigenaemia nor EBV replication in the blood was observed. Seven patients had positive polyoma BK virus replication in the blood but none developed polyoma virus-associated nephropathy (PVAN). Protocol biopsies revealed rejection Banff IIa in three patients on Day 7, and in one patient after 3 and 6 months. Banff Ia rejection was found in five patients. All rejection episodes resolved. Mild signs of chronic antibody-mediated rejection were observed in five patients. Conclusions. ABO-incompatible kidney transplantation seems to be successful and safe. Modifications of the current protocol may be possible and may further reduce potential side effects and cost

Long-term course of haemoglobin and ferritin values in high-frequency donors of whole blood and double erythrocyte apheresis

Background: High-intensity donation is a risk factor for iron deficiency in blood donors. Interdonation intervals for whole blood (WB) donation and double unit red blood cell apheresis (2RBC) vary among countries. We retrospectively evaluated the course of haemoglobin (Hb) and ferritin values in men regularly donating WB 4 times a year or 2RBC twice a year (i.e., maximal frequency) over a period of 48 months. Methods: Data of male donors with 16 WB or 8 2RBC consecutive donations were analysed. The minimum Hb levels for WB donation and 2RBC apheresis (collection of 360 mL RBC) were 135 and 140 g/L, respectively. There was no lower limit set for ferritin, and no iron was substituted. Results: We identified 294 WB (mean age 53 years, SD 11) and 151 2RBC donors (mean age 48 years, SD 9) who donated at a mean interval of 97 (SD 18) and 201 days (SD 32), respectively, between January 1, 2008, and December 31, 2013. At baseline, Hb and ferritin values were lower in WB donors compared to 2RBC donors, with a mean Hb of 153 g/L (SD 13) versus 159 g/L (SD 8) and a mean ferritin of 44 μg/L (SD 52) versus 73 μg/L (SD 56; p < 0.001 for both parameters), respectively. Ferritin was below 15 μg/L in 40 WB (14%) and in 4 (3%) 2RBC donors. In WB donors, the mean Hb levels at baseline versus last donation showed no significant difference (153 vs. 152g/L, p = 0.068), whereas the mean ferritin levels decreased significantly (44 vs. 35 μg/L, p < 0.001). The 2RBC donor group displayed a statistically different decrease in both the mean Hb levels (158 vs. 157 g/L; p < 0.05) and the mean ferritin levels (73 vs. 66 μg/L; p = 0.052). The lowest Hb was measured at the 11th WB donation (152 g/L; p < 0.05) and at the 4th 2RBC apheresis (157 g/L; p < 0.05). There was no deferral due to low Hb at any time. The lowest ferritin was shown at the 4th WB (37 μg/L) and at the 3rd 2RBC donation (60 μg/L), respectively. At the last visit, ferritin was below 15 μg/L in 23 WB donors (8%) and in 2 2RBC donors (1%). Conclusions: High-intensity male donors with an interdonation interval of 12 weeks for WB donation and 24 weeks for 2RBC apheresis maintain acceptable Hb levels and, after an initial decline,stable ferritin levels despite ongoing blood donation

Potent neutralization by monoclonal human IgM against SARS-CoV-2 is impaired by class switch.

To investigate the class-dependent properties of anti-viral IgM antibodies, we use membrane antigen capture activated cell sorting to isolate spike-protein-specific B cells from donors recently infected with SARS-CoV-2, allowing production of recombinant antibodies. We isolate 20, spike-protein-specific antibodies of classes IgM, IgG, and IgA, none of which shows any antigen-independent binding to human cells. Two antibodies of class IgM mediate virus neutralization at picomolar concentrations, but this potency is lost following artificial switch to IgG. Although, as expected, the IgG versions of the antibodies appear to have lower avidity than their IgM parents, this is not sufficient to explain the loss of potency

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility

Current hepatitis E virus seroprevalence in Swiss blood donors and apparent decline from 1997 to 2016

Background and aimHepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1-21.8) of the 3,609 blood samples collected in 2014-16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8-33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018

Current and emerging developments in subseasonal to decadal prediction

Weather and climate variations of subseasonal to decadal timescales can have enormous social, economic and environmental impacts, making skillful predictions on these timescales a valuable tool for decision makers. As such, there is a growing interest in the scientific, operational and applications communities in developing forecasts to improve our foreknowledge of extreme events. On subseasonal to seasonal (S2S) timescales, these include high-impact meteorological events such as tropical cyclones, extratropical storms, floods, droughts, and heat and cold waves. On seasonal to decadal (S2D) timescales, while the focus remains broadly similar (e.g., on precipitation, surface and upper ocean temperatures and their effects on the probabilities of high-impact meteorological events), understanding the roles of internal and externally-forced variability such as anthropogenic warming in forecasts also becomes important. The S2S and S2D communities share common scientific and technical challenges. These include forecast initialization and ensemble generation; initialization shock and drift; understanding the onset of model systematic errors; bias correct, calibration and forecast quality assessment; model resolution; atmosphere-ocean coupling; sources and expectations for predictability; and linking research, operational forecasting, and end user needs. In September 2018 a coordinated pair of international conferences, framed by the above challenges, was organized jointly by the World Climate Research Programme (WCRP) and the World Weather Research Prograame (WWRP). These conferences surveyed the state of S2S and S2D prediction, ongoing research, and future needs, providing an ideal basis for synthesizing current and emerging developments in these areas that promise to enhance future operational services. This article provides such a synthesis

The Remarkable Journey of a Low-Frequency Alloantibody

Herein we describe a case of febrile non-hemolytic reaction (FNHTR) in a 64-year-old male 20 min after the transfusion of one red blood cell unit. 20 days prior the patient had undergone an allogeneic hematopoietic stem cell transplantation (HCT) from an unrelated donor with minor ABO disparity. The patient had been treated for plasma cell myeloma with multiple transfusions in the past, but no transfusion reactions or alloimmunization had been reported