[Multidisciplinary management of voluntary pink oleander poisoning: How to estimate the quantities ingested?] / Prise en charge multidisciplinaire d'une intoxication volontaire au laurier rose : comment estimer les quantités ingérées ?

This is a case of voluntary ingestion of Nerium oleander leaves in an adolescent requiring the use of atropine and emergency chartering of antidigoxin antibodies (Digifab®) due to the difficulty of assessing oleandrin level and associated toxicity. Upon hospital admission, a digoxinemia was performed (0.44µg/mL) and the presence of oleandrine was detected. Oleandrin levels at toxic levels may be suspected by a measure of blood digoxin and explain the patient's clinical signs, which could adapt the therapeutic management.

[Reevaluating the shelf life of sterilized packaged items via a risk-analysis study]. / Réévaluation de la durée de péremption des dispositifs médicaux restérilisables via une analyse de risques.

In the hospital, all the reprocessed reusable medical devices (RMD) are conditioned with a sterile barrier system and a protection package and they expire after three months. The objective of this study is to reevaluate this shelf life via a risk-analysis study focusing on the steps whose malfunction can fail RMD sterility. The first step is analysing current conditions of packaging, transportation and storage of RMD. The risk-analysis study has been built on French National Authority for Health template. Risks are prioritized in three categories: non critical risks, risks that need to be kept track of and risks to manage as a priority. Storage conditions have been evaluated in 52 wards in ten different structures. All of the wards respect the paper side of the pouches. They were stored in a dedicated storage unit in 85 % of the units. They were closed at the moment of the observation in 58 % of the cases. RMD were stacked in 81 % of the units and 36 % of them had at leat one expired RMD in their storage unit. The risk-analysis study identified two risks to manage as a priority. Some RMD were damaged during transportation to a subcontractor hospital. This step is barely manageable due to the human factor but the transport rules have been reminded in order to lower the risks on the materials. The operating rooms common storage include shelves that alter pouches and wraps, but a replacement of equipments is under discussion. Thanks to a better understanding of RMD circuit current conditions, allowing a better control of sensitive steps, their shelf life is reevaluated up to 6 months for containers and 4 months for other pouches.

Obesity phenotype and patient-reported outcomes in moderate and severe chronic kidney disease: a cross-sectional study from the CKD-REIN cohort study.

PURPOSE: To evaluate the association between obesity phenotypes and health-related quality of life (HRQoL) in non-dialysis-dependent CKD patients. METHODS: Data from the national CKD-REIN cohort which included 3033 patients with stage 3-4 CKD were used. Patients were divided into three groups: non-obese (NO) patients (BMI < 30 kg/m2), metabolically healthy obese (MHO) (BMI ≥ 30 kg/m2 and ≤ 1 criterion NCEP/ATP III), and metabolically unhealthy obese (MUO) (BMI ≥ 30 kg/m2 and ≥ 2 criteria NCEP/ATP III). HRQoL was measured by the KDQOL-36™ which comprised three disease-specific dimensions: symptoms, effects, and burden and two summaries scores: physical (PCS) and mental (MCS). We used a mixed effect model with adjustment on sociodemographic characteristics and comorbidities. RESULTS: A total of 2693 patients completed the self-administered questionnaires. MHO patients accounted for 3.4% of the cohort and for 12% of obese patients. In the NO group, average HRQoL scores were 77.2 ± 15.9 for symptoms, 83.5 ± 16.5 for effects, 76.8 ± 22.7 for burden, 43.5 ± 9.7 for PCS, and 47.9 ± 7.0 for MCS. In the multivariate analysis, scores were similar in MHO and NO patients, but significantly different with those in MUO patients: symptoms (- 0.7; p = 0.71 vs. - 3.0; p = 0.0025), effects (+ 1.2; p = 0.57 vs. - 4.3; p < 0.0001), burden (+ 2.7; p = 0.31 vs. - 3.6; p = 0.0031), and PCS (- 0.6; p = 0.58 vs. - 4.3; p < 0.0001). MCS was not associated with obesity phenotypes. CONCLUSIONS: This study demonstrated an association between obesity phenotypes and QoL in non-dialysis-dependent CKD patients. MUO patients had worse QoL than NO and MHO patients even after adjustment on comorbidities.

JAMI: a Java library for molecular interactions and data interoperability.

BACKGROUND: A number of different molecular interactions data download formats now exist, designed to allow access to these valuable data by diverse user groups. These formats include the PSI-XML and MITAB standard interchange formats developed by Molecular Interaction workgroup of the HUPO-PSI in addition to other, use-specific downloads produced by other resources. The onus is currently on the user to ensure that a piece of software is capable of read/writing all necessary versions of each format. This problem may increase, as data providers strive to meet ever more sophisticated user demands and data types. RESULTS: A collaboration between EMBL-EBI and the University of Cambridge has produced JAMI, a single library to unify standard molecular interaction data formats such as PSI-MI XML and PSI-MITAB. The JAMI free, open-source library enables the development of molecular interaction computational tools and pipelines without the need to produce different versions of software to read different versions of the data formats. CONCLUSION: Software and tools developed on top of the JAMI framework are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI avoids the requirement to chain conversions between formats in order to reach a desired output format and prevents code and unit test duplication as the code becomes more modular. JAMI's model interfaces are abstracted from the underlying format, hiding the complexity and requirements of each data format from developers using JAMI as a library.

Encompassing new use cases - level 3.0 of the HUPO-PSI format for molecular interactions.

BACKGROUND: Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes. RESULTS: The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal. CONCLUSIONS: PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and download.

[Berger's disease associated to an adalimumab-treated rheumatoid arthritis]. / Maladie de Berger au cours d'une Polyarthrite Rhumatoïde traitée par Adalimumab.

Berger's disease is characterized by deposits of immunoglobulin A in the glomerular mesangium. We report a case of a patient who was treated by adalimumab for a rheumatoid arthritis (RA). The patient is 45 years old and is treated for RA since 1996. Adalimumab was started after the failure of several treatments. Biological and clinical response to adalimumab were excellent. A nephrotic syndrome was diagnosed during the patient follow-up. Adalimumab was stopped since it was suspected to be responsible of these symptoms. Berger's disease was diagnosed thanks to a renal biopsy. The nephrotic syndrome was treated with corticosteroids, then tocilizumab was used to treat RA. TNF-alpha inhibitors are well known for inducing kidneys' adverse reactions (ADR). Usually, they appear shortly after the beginning of a treatment. Adalimumab has already been described in studies for inducing similar kidneys' adverse drug reactions. These ADR are often associated with systemic disease outbreak. It is difficult to assert that adalimumab or RA was responsible of the ADR that we noticed in our patient. It is usually admitted that these ADR are uncommon when the RA is controlled.

[Prospective evaluation of the direct costs of prostate enucleation by the HoLEP® laser during the learning curve period]. / Évaluation prospective des coûts directs de l'énucléation prostatique par le laser HoLEP® pendant la courbe d'apprentissage.

OBJECTIVE: Holmium laser enucleation of the prostate (HoLEP) has been shown to be effective in treating large prostates compared to prostate transurethral resection (TURP). There are no published data evaluating specifically the impact of the learning curve on the direct costs of HoLEP. The objective of this study was to evaluate the direct costs generated by the use of HoLEP laser during the learning curve period. METHOD: The costs of all medical devices (DM) and drugs used, pre- and post-operative parameters during surgery have been prospectively collected between March and October 2016. RESULTS: A total of 32 patients were included in the study with a mean age of 70.8 years and a mean prostate volume of 68.6 cm3. The mean cost of anesthesia was 39.0 € and that of drugs and DM used for surgery was 257.95 € but could reach 470.76 € in case of conversion to bipolar resection. The mean duration of enucleation and morcellation was 150minutes with a mean weight of enucleated specimens of 40.4g. The total mean duration of patient care was 197minutes at an estimated hourly cost of € 636. CONCLUSIONS: Despite some limitations, this study makes it possible to analyze the direct costs of the management of benign prostatic hypertrophy using HoLEP, an innovative surgical technique, and to specify that these costs are more related to bipolar conversion and voluminous adenomas especially during the learning curve. LEVEL OF EVIDENCE: 5.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients.

In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10 IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (-0.066 vs -0.027 PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log10 IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.

Homozygous 16p13.11 duplication associated with mild intellectual disability and urinary tract malformations in two siblings born from consanguineous parents.

The use of array-comparative genomic hybridization (array-CGH) in routine clinical work has allowed the identification of many new copy number variations (CNV). The 16p13.11 duplication has been implicated in various congenital anomalies and neurodevelopmental disorders, but it has also been identified in healthy individuals. We report a clinical observation of two brothers from related parents each carrying a homozygous 16p13.11 duplication. The propositus had mild intellectual disability and posterior urethral valves with chronic renal disease. His brother was considered a healthy child with only learning disabilities and poor academic performances. However, a routine medical examination at 25-years-old revealed a mild chronic renal disease and ureteropelvic junction obstruction. Furthermore, the father presented with a unilateral renal agenesis, thus it seemed that a "congenital anomalies of kidney and urinary tract" (CAKUT) phenotype segregated in this family. This may be related to the duplication, but we cannot exclude the involvement of additional genetic or non-genetic factors in the urological phenotype. Several cohort studies showed association between this chromosomal imbalance and different clinical manifestations, but rarely with CAKUT. The duplication reported here was similar to the larger one of 3.4 Mb previously described versus the more common of 1.6 Mb. It encompassed at least 11 known genes, including the five ohnologs previously identified. Our observation, in addition to expanding the clinical spectrum of the duplication provides further support to understanding the underlying pathogenic mechanism.

Embolization of renal arteries before transplantation in patients with polycystic kidney disease: a single institution long-term experience.

PURPOSE: We aimed to retrospectively assess the long-term safety and efficacy of embolization of renal arteries (ERA) in patients with polycystic kidney disease (PKD) before renal transplantation. MATERIAL AND METHODS: Between January 2008 and November 2013, 82 ERA procedures were performed on 76 kidneys in 73 patients (mean age 53 years, range: 34-72). All patients had terminal-stage PKD and were under dialysis and on the renal transplant waiting list with a temporary contraindication due to excessive renal volume. RESULTS: ERA was considered successful in 89.5% (68/76) of embolized kidneys, meaning that the temporary contraindication for transplantation could be withdrawn for 65 patients (on average 5.6 months, range: 2.8-24.3, after ERA). Mean volume reduction was 40 (range: 2-69) at 3 months and 59% (35-86) thereafter (both p < 0.001). Post-embolization syndrome occurred after 15 of 82 procedures (18.3%). The severe complication rate was 4.9%. Forty-three (67.7%) transplantations were successfully conducted after ERA, with a mean follow-up of 26.2 months (range: 1.8-59.5), and the estimated 5-year graft survival rate was 95.3% [95% CI: 82.7-98.8]. CONCLUSIONS: ERA is a safe and effective alternative to nephrectomy before renal transplantation in patients with PKD. KEY POINTS: • Embolization of non-functioning polycystic kidneys allowed transplantation in 89.5% of cases. • Technical failure rate was 7.9% after embolization, irrespective of the technique used. • Post-embolization syndrome occurred after 18.3% of the procedures. • A low rate of severe complications (4.9%) was observed after renal embolization.

[Comparison between implantation costs of peripherally inserted central catheter and implanted subcutaneous ports]. / Comparaison entre le coût d'une pose de cathéter veineux central d'insertion périphérique et d'une chambre implantable.

INTRODUCTION: Peripherally Inserted Central Catheter or PICC Line and implanted subcutaneous ports are two types of central catheters allowing drug administration and blood samplings. These two devices are very controversial (because of infectious and thrombotic complications), it seemed interesting to estimate their cost of implantation and to correlate them with the reimbursement by the Health Insurance. MATERIALS AND METHODS: Direct (material and drugs) and indirect (use of the room and staff) costs were prospectively evaluated for PICC Lines and implanted subcutaneous ports. RESULTS: The global costs of the implantation of a PICC Line and of an implanted subcutaneous port in the interventional radiology room and in the operating room were respectively evaluated at 220.2 €, 286.6 € and 666.3 €. DISCUSSION-CONCLUSION: Only a PICC Line in outpatients can be reimbursed by the health insurance; which amounts to 110.4 €. The establishment therefore loses money with every implantation. However, PICC Lines offer to the patients a fast access to a central venous way and thus an optimal therapeutic care, fulfilling one of the main missions of the public health institutions. Implanted subcutaneous ports are economically worth being implanted only in ambulatory inpatients. Its implantation in radiology seemed more profitable because the indirect costs were much more moderate.

Evaluation of the AltoStar AM16 system for the quantitation of AdV, CMV and HHV-6 DNA from clinical specimens.

The vulnerability of immunocompromised patients to common or opportunistic viral infections is particularly high. The quantitation of viral load in clinical specimens is important for the diagnosis and management of the infection and reactivation in this patient population, particularly transplant recipients. As the new regulation "IVDR" regarding in vitro diagnosis methods is about to come into effect in France, diagnostic laboratories have to implement methods and systems compatible with this new regulation. Technical performance of the AltoStar® Adenovirus (AdV), Cytomegalovirus (CMV) and human Herpesvirus-6 (HHV-6) DNA PCR Kits 1.5 was assessed on the AltoStar Automation system AM16 using reference kits in 146 clinical samples. Overall agreement in clinical specimens was 87.5 % (28/32), 96.8 % (62/64), 100 % (22/22), 100 % (28/28) and 92.8 % (26/28) for AdV, CMV (WB samples and other matrices), HHV-6 A&B respectively. Quantitative results were highly correlated and estimated to be equivalent within a 0.057-0.648 log-amount difference.We found that altona kits on The AltoStar AM16 system are suitable for clinical monitoring of AdV, CMV and HHV-6 in immunocompromised hosts.

ViralORFeome: an integrated database to generate a versatile collection of viral ORFs.

Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such 'ORFeome' resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway(R) system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins.

Household transmission of haemolytic uraemic syndrome associated with Escherichia coli O104:H4, south-western France, June 2011.

Following the outbreak of haemolytic uraemic syndrome (HUS) on June 2011 in south-western France, household transmission due to Escherichia coli O104:H4 was suspected for two cases who developed symptoms 9 and 10 days after onset of symptoms of the index case. The analysis of exposures and of the incubation period is in favour of a secondary transmission within the family. Recommendations should be reinforced to prevent person-to-person transmission within households.

[Proposal of a costing method for the provision of sterilization in a public hospital]. / Proposition d'une méthode de facturation de la prestation de stérilisation dans un centre hospitalier public.

INTRODUCTION: To refine the billing to institutions whose operations of sterilization are outsourced, a sterilization cost approach was developed. The aim of the study is to determine the value of a sterilization unit (one point "S") evolving according to investments, quantities processed, types of instrumentation or packaging. MATERIALS AND METHODS: The time of preparation has been selected from all sub-processes of sterilization to determine the value of one point S. The time of preparation of sterilized large and small containers and pouches were raised. The reference time corresponds to one bag (equal to one point S). Simultaneously, the annual operating cost of sterilization was defined and divided into several areas of expenditure: employees, equipments and building depreciation, supplies, and maintenance. RESULTS: A total of 136 crossing times of containers were measured. Time to prepare a pouch has been estimated at one minute (one S). A small container represents four S and a large container represents 10S. By dividing the operating cost of sterilization by the total number of points of sterilization over a given period, the cost of one S can be determined. DISCUSSION/CONCLUSION: This method differs from traditional costing method in sterilizing services, considering each item of expenditure. This point S will be the base for billing of subcontracts to other institutions.

[Tuberous sclerosis complex: A review]. / Sclérose tubéreuse de Bourneville : mise au point.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects different organs and caused by loss-of-function mutations in one of two genes: TSC1 or TSC2. TSC1 or TSC2 gene mutation lead to dysfunction of hamartin or tuberin, respectively. Hamartin and tuberin form a protein complex that helps regulate cellular proliferation. These proteins form a complex that constitutively inhibits the mammalian target of rapamycin (mTOR) signaling pathway, leading to permanent activation of mTOR signaling within all TSC-associated lesions. Major features of TSC include tumors of the brain, skin, heart, lungs and kidneys, seizures and TSC-associated neuropsychiatric disorders, which can include autism spectrum disorder and cognitive disability. These disorders are usually diagnosed in children and adults. Specific guidelines for diagnosis, surveillance, and management have been proposed by the International Tuberous Sclerosis Complex Consensus Group. Several randomized controlled trials led to regulatory approval of the use of mTOR inhibitors for the treatment of renal angiomyolipomas, brain subependymal giant cell astrocytomas, refractory epilepsy and pulmonary lymphangioleiomyomatosis.

System-level comparison of protein-protein interactions between viruses and the human type I interferon system network.

Innate immunity has evolved complex molecular pathways to protect organisms from viral infections. One pivotal line of cellular defense is the induction of the antiviral effect of interferon. To circumvent this primary response and achieve their own replication, viruses have developed complex molecular strategies. Here, we provide a systems-level study of the human type I interferon system subversion by the viral proteome, by reconstructing the underlying protein-protein interaction network. At this network level, viruses establish a massive and a gradual attack, from receptors to transcription factors, by interacting preferentially with highly connected and central proteins as well as interferon-induced proteins. We also demonstrate that viruses significantly target 22% of the proteins directly interacting with the type I interferon system network, suggesting the relevance of our network-based method to identify new candidates involved in the regulation of the antiviral response. Finally, based on the comparative analysis of interactome profiles across four viral families, we provide evidence of common and differential targeting strategies.

Serological and immunochemical analysis of the products of a single HLA DR-alpha and DR-beta chain gene expressed in a mouse cell line after DNA-mediated cotransformation reveals that the beta chain carries a known supertypic specificity.

Using a mouse cell line transformed with and expressing a single HLA DR-alpha and DR-beta chain gene, we present evidence that the product of the DR-beta chain gene carries a supertypic determinant, BR3, previously defined by serology. The amino acid sequence of this beta chain gene is determined from the DNA sequence. Another DR-associated supertypic specificity defined by monoclonal antibody MCS7 was not encoded by this DR-beta chain gene. This provides formal proof that a supertypic specificity can be associated with a product of a distinct DR-beta locus. We propose that haplotypes sharing such specificities are evolutionarily related.

Measles virus nucleocapsid protein binds to FcgammaRII and inhibits human B cell antibody production.

Despite the development of an efficient specific immune response during measles virus (MV) infection, an immunosuppression occurs contributing to secondary infections. To study the role of nucleocapsid protein (NP) in MV-induced immunosuppression, we produced recombinant MV NP. Purified recombinant NP exhibited biochemical, antigenic, and tridimensional structure similar to viral NP. By flow cytometry, we showed that viral or recombinant NP bound to human and murine B lymphocytes, but not to T lymphocytes. This binding was specific, independent of MHC class II expression, and dependent of the B lymphocyte activation state. The murine IIA1. 6 B cell line, deficient in the Fc receptor for IgG (FcgammaRII) expression, did not bind NP efficiently. Transfected IIA1.6 cells expressing either murine FcgammaRIIb1 or b2, or human FcgammaRIIa, b1*, or b2 isoforms efficiently bound NP. Furthermore, this binding was inhibited up to 90% by monoclonal antibodies 2.4G2 or KB61 specific for murine and human FcgammaRII, respectively. Finally, the in vitro Ig synthesis of CD40- or Ig-activated human B lymphocytes in the presence of interleukin (IL)-2 and IL-10 was reduced by 50% in the presence of recombinant NP. These data demonstrate that MV NP binds to human and murine FcgammaRII and inhibits in vitro antibody production, and therefore suggests a role for NP in MV-induced immunosuppression.