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We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although varicelliform Kaposi eruption is a well-known complication of dermatoses, it has not been widely investigated., Aim: To investigate features of dermatoses and herpes superinfection in patients hospitalized in a dermatology department., Patients and Methods: We performed a single-centre, retrospective study between 2008 and 2014 that included cases of Kaposi varicelliform eruptions defined by positive PCR of an unconventional site of herpetic recurrence in a setting of active dermatitis. A record was compiled of each case giving details of the history, clinical and laboratory findings, therapeutic data and outcome., Results: Thirty-four cases of Kaposi varicelliform eruptions in 30 subjects were studied. Mean age at diagnosis was 63.3±24.2 years. The underlying dermatoses were as follows: 7 pemphigus, 6 bullous pemphigoid, 3 cicatricial pemphigoid, 3 atopic dermatitis, 1 Darier disease, and 14 other dermatoses. Patients presented with skin (94.1 %) or mucous membrane lesions (62 %), mostly erosive (79 %), vesicular (27 %) or bullous (41 %), often painful (56 %) or pruritic (29 %). At diagnosis, 41.2 % were undergoing systemic immunotherapy and 24 % were on topical corticosteroids. PCR was positive for HSV1 in 20 cases and for HSV2 in 4 cases, and indeterminate in 10 cases. Lymphocytopenia was seen in 59 % of cases. The majority of patients received treatment. Nine patients experienced at least one relapse., Conclusion: Our study confirms the over-representation not only of the expected dermatoses (pemphigus and atopic dermatitis), but also of others such as pemphigoid and acute dermatoses; these results should be investigated in a more systematic prospective study., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Antisynthetase syndrome (aSS) is characterized by the association of interstitial lung disease and myositis with anti-tRNA synthetase autoantibodies. Immune mechanisms leading to aSS could be initiated in the lungs, but the role of NK cells has not yet been studied. Both extensive NK cell phenotype and functions were compared between 33 patients and 26 controls. Direct and redirected polyfunctionality assays (degranulation and intracellular production of TNF-α and IFN-γ) were performed spontaneously or after IL-12 plus IL-18 stimulation in the presence of K562 or P815 target cells, respectively. NK cells from inactive patients showed normal phenotype, whereas active aSS revealed a differentiated NK cell profile, as indicated by increased CD57 and Ig-like transcript 2 and an inability to produce IFN-γ (p = 0.002) compared with controls. Importantly, active aSS was more specifically associated with a significant NKp30 decrease (p = 0.009), although levels of mRNA and intracellular protein were similar in aSS and healthy controls. This NKp30 decrease was strongly correlated with reduced NK cell polyfunctionality in both direct and redirected killing assays with anti-NKp30 Abs (p = 0.009 and p = 0.03, respectively), confirming its important impact in aSS. Histological studies revealed massive infiltrations of NK cells inside the lungs of aSS patients (148 versus 11/mm(2)). Taken together, these data suggest that NK cells and NKp30 could play a role in aSS pathogenesis., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Background: PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription factor autoimmune regulator (AIRE) to promote central T-cell tolerance., Objective: We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity associated with decreasing T- and B-cell counts over time that had been diagnosed in 2 unrelated patients., Methods: Genetic, molecular, and functional analyses were performed to characterize an inflammatory disease evocative of a combined immunodeficiency., Results: We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA double-strand break repair and V(D)J recombination. Whole-blood mRNA analysis revealed a strong interferon signature. On activation, memory T cells displayed a skewed cytokine response typical of TH2 and TH1 but not TH17. Moreover, mutated DNA-PKcs did not promote AIRE-dependent transcription of peripheral tissue antigens in vitro. The latter defect correlated in vivo with production of anti-calcium-sensing receptor autoantibodies, which are typically found in AIRE-deficient patients. In addition, 9 months after bone marrow transplantation, patient 1 had Hashimoto thyroiditis, suggesting that organ-specific autoimmunity might be linked to nonhematopoietic cells, such as AIRE-expressing thymic epithelial cells., Conclusion: Deficiency of DNA-PKcs, a key AIRE partner, can present as an inflammatory disease with organ-specific autoimmunity, suggesting a role for DNA-PKcs in regulating autoimmune responses and maintaining AIRE-dependent tolerance in human subjects., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: CXCR4 is a chemokine receptor with multiple effects on the immune system, upregulated in patients with SLE, and correlated with disease severity., Objective: This study has investigated whether the levels of CXCR4 expressed on leucocyte subsets in lupus patients are correlated with the efficacy and the safety of the influenza vaccine., Methods: Twenty-seven patients were vaccinated and vaccine immunogenicity and tolerance were evaluated. CXCR4 was assayed on leucocyte subsets and correlated with clinical and immunological signs of diseases activity., Results: A significant increase in the titres of antibodies to the three viral strains was observed along with trends towards an increased vaccine efficacy in patients with quiescent disease vs patients with active disease. Recent flu vaccine history and, to a lesser extent, immunosuppressive treatment may influence vaccine immunogenicity. Influenza immunization was not associated with clinical side-effects or clinical lupus flare but with an increase in rheumatoid factor levels. Our study also confirms the correlation of CXCR4 expression with biological autoimmunity as shown by the correlation between the percentage of CXCR4-positive T cells and the ANA titres at D0, and the reverse correlation between CXCR4 expression and vaccine immunogenicity as demonstrated by the higher percentage of CXCR4-positive T cells at D0 and D30 in non-responders vs responders., Conclusion: Altogether, our study confirms the efficacy and the safety of flu vaccine in SLE patients, highlights the role of CXCR4 as a surrogate marker for autoimmunity in lupus and shows that CXCR4 expression on T cells is predictive of vaccine efficacy in SLE patients., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

During the 2009-2010 influenza pandemic, pregnant women were identified at high risk for severe infection. In case of influenza-like illness they were systematically treated with oseltamivir. When performed, virological diagnosis showed that some of these women were not influenza-infected. The objectives of the study were to identify viruses which could induce an influenza-like illness in pregnant women during the 2009-2010 pandemic, then to establish possible links between detected viruses and symptoms, and then characterize human rhinoviruses (HRV) strains detected in some samples. Nasal swabs from 78 pregnant women presenting with influenza-like illness and previously tested for influenza virus by RT-PCR in 2009-2010 were further assayed by multiplex RespiFinder assay and bocavirus PCR to search for 13 other viruses. Genotyping of HRV strains was carried out using partial genomic sequencing in the VP4/VP2 region. Influenza A virus infection was confirmed in 33 women (42%). Non-influenza viruses were detected in 18 additional cases (23%). Rhinoviruses were the most numerous (13%) and belonged to 9 different genotypes distributed between the 3 genogroups. When comparing symptoms observed in influenza-infected women and women infected by other viruses, shivers were more frequent in the former group (P=0.02), and expectorations in the latter (P=0.03). During the influenza pandemic 2009-2010, non-influenza viruses and mostly rhinoviruses were an underestimated cause of influenza-like illness in pregnant women. Viral diagnosis should help to stop empiric oseltamivir therapy in influenza-negative patients and antibiotic treatment in patients infected with a non-influenza virus., (Copyright © 2013 Wiley Periodicals, Inc.)

Background & Aims: Hepatitis B virus (HBV) infection is more frequent in kidney recipients than in the general population with a higher rate of liver-related morbidity and mortality. We evaluated the benefit associated with HBV viral suppression by nucleos(t)ide analogues treatment in HBV-infected kidney recipients., Methods: This retrospective study included 42 HBsAg-positive kidney recipients, 33 males, 9 females, median age 54 years, followed up during a mean of 15.4±11.8 years after kidney transplantation. Mean treatment duration by single or combined nucleos(t)ide analogues was 6.8±4.3 years. Fibrosis, before treatment, according to Metavir score was: F4 for 6 patients, F3 for 10, F2 for 6, and F0-F1 for 20 patients. The primary end point, the patient survival, was defined as patient death or liver transplantation, the secondary end point was graft survival., Results: HBV DNA at the last evaluation was undetectable (<12 IU/ml) in 92.8% of patients. During the follow-up, 8 patients died (17.7%), death being related to hepatocellular carcinoma in 4 (9.5%), including 1 patient with baseline mild fibrosis, and to extrahepatic causes in 4. This mortality rate is strikingly lower than that previously reported in HBV-infected kidney recipients before oral antiviral therapies. Graft survival seems to be improved when compared to the former series., Conclusions: Suppression of HBV replication associated with nucleo(s)tide analogues treatment improves the survival of HBV-infected kidney recipients. Viral suppression does not exclude regular follow-up given the risk of occurrence of hepatocellular carcinoma even in non-cirrhotic patients., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Although adherence is of major importance in long-term treatments, few studies have been published regarding the use of anti-HBV analogues in clinical practice. The aim of this study was to evaluate adherence to anti-HBV analogues and associated virological suppression., Methods: A cross-sectional study was performed between 1 January 2009 and 15 July 2009 in Cochin Hospital, Paris, France. It included all patients being treated with anti-HBV analogues for at least three months, who were without coinfection (HIV, HCV or HDV) and who had not received organ transplants. At the time of enrolment, HBV viral load, analogue regimen and self-reported adherence were collected prospectively. Patients were classified as non-adherent, or moderately or totally adherent using a score based on analysis of self-reports. Other data were obtained retrospectively., Results: Among the 190 patients meeting the inclusion criteria, 33% were initially hepatitis B e antigen-positive and 50% had extensive fibrosis or cirrhosis. Pretreatment viral load was 6.0 log IU/ml (median). The median duration of treatment was 52 months. At enrolment, 61%, 32% and 7% of patients were classified as totally adherent, moderately adherent and non-adherent, respectively. Complete virological suppression (HBV DNA<12 IU/ml) was observed in 83% of patients at enrolment. In the multivariate analysis, lack of virological suppression was associated with an increased pretreatment viral load, with no change in analogue regimen and is classified as non-adherent., Conclusions: Adherence seems to be an independent factor associated with virological suppression during anti-HBV analogue treatment. Therapeutic education and a systematic evaluation of adherence using self-reports should be promoted to assure long-term anti-HBV analogue efficacy in clinical practice.

It remains unclear how the detection of hepatitis B core antibody (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) should be interpreted and whether all patients with this pattern need to be tested for hepatitis B virus (HBV)-DNA. This study aimed at reassessing the significance of 'anti-HBc alone' in unselected sera referred to the clinical laboratory and determining whether significant HBV viraemia can be found in this setting. Of the 6431 patients tested for HBsAg, total anti-HBc and anti-HBs in a Paris hospital over a 1-year period, 362 (5.6%) had 'anti-HBc alone' (24.8% of anti-HBc-positive patients). Only 11 of the 362 sera (3.0%) were found to be false positive. One patient was in the resolving phase of acute hepatitis B. HBV-DNA was detected in 10 of 362 (2.8%) patients, using a commercial standardized assay (threshold: 350 IU/mL). Viral loads exceeded 10(4) copies/mL in 6 of 10 patients. Mutations in the HBsAg immunodominant region were identified in seven of the viraemic patients. HBsAg was detected in only two cases when retested by one of the latest, multivalent assays. Neither human immunodeficiency virus nor hepatitis C virus serostatus distinguished between patients with and without HBV-DNA. In conclusion, 'anti-HBc alone' should be considered a risk marker for a so-called 'false occult' HBV infection with significant viraemia. Indeed, results in this hospital population indicate that a small proportion of patients with 'anti-HBc alone' have high viral loads, revealing the occurrence of infection with HBV mutants that escape detection even by multivalent HBsAg assays., (© 2011 Blackwell Publishing Ltd.)

Background & Aims: Although hepatitis C virus (HCV) can be grown in the hepatocarcinoma-derived cell line Huh-7, a cell-culture model is needed that supports its complete, productive infection cycle in normal, quiescent, highly differentiated human hepatocytes. We sought to develop such a system., Methods: Primary cultures of human adult hepatocytes were inoculated with HCV derived from Huh-7 cell culture (HCVcc) and monitored for expression of hepatocyte differentiation markers and replication of HCV. Culture supernatants were assayed for HCV RNA, core antigen, and infectivity titer. The buoyant densities of input and progeny virus were compared in iodixanol gradients., Results: While retaining expression of differentiation markers, primary hepatocytes supported the complete infectious cycle of HCV, including production of significant titers of new infectious progeny virus, which was called primary-culture-derived virus (HCVpc). Compared with HCVcc, HCVpc had lower average buoyant density and higher specific infectivity; this was similar to the characteristics of virus particles associated with the very-low-density lipoproteins that are produced during in vivo infection. These properties were lost after re-culture of HCVpc in poorly differentiated Huh-7 cells, suggesting that authentic virions can be produced only by normal hepatocytes that secrete authentic very-low-density lipoproteins., Conclusions: We have established a cell-culture-based system that allows production of infectious HCV in physiologically relevant human hepatocytes. This provides a useful tool for the study of HCV interactions with its natural host cell and for the development of antiviral therapies., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To report three cases of herpetic infection in recipients of organ-cultured donor corneas among 586 consecutive corneal transplantation procedures., Methods: Three patients with no history of symptomatic herpes infection underwent corneal transplantation for keratoconus (2 patients) and Fuchs dystrophy (1 patient). Two patients developed keratouveitis and primary graft failure. The third patient developed dendritic keratitis in the graft. Culture of corneal scrapings and the patient's bandage contact lens were positive for herpes simplex virus type 1 (HSV-1). Donor and recipient sera were tested for HSV serology by EIA. Recipient corneal buttons were studied by means of transmission electron microscopy and immunohistochemistry. The three HSV-1 strains were genotyped by sequencing part of a variable antigenic domain of glycoprotein B (gB)., Results: None of the donor corneas showed endothelial cell necrosis after organ culture. All keratoplasties performed with the three mate donor corneas had an uncomplicated course. All three donor sera were positive for HSV. Preoperative recipient sera were positive for HSV. Analysis of the recipient corneal buttons showed no evidence of herpetic infection. Sequence analysis revealed three different gB genotypes., Conclusion: Ascertaining that a postoperative herpetic infection in a corneal transplant originates from the donor tissue is still difficult. Although some features of the reported cases suggest donor-to-host transmission of herpes simplex virus, the recipients could have been the source of the virus.

Objective: Varicella, resulting from primary infection by varicella zoster virus, carries a risk of severe congenital varicella. Prenatal diagnosis is rarely applied because methods remain to be validated., Study Design: From 1989 to 1994, 107 women contracted clinical varicella before 24 weeks of pregnancy. Amniocentesis was performed in all cases, with simultaneous fetal blood sampling in 82 cases. Virus was detected in amniotic fluid by cell culture inoculation and polymerase chain reaction. Fetal blood was tested for anti-varicella zoster virus immunoglobulin M., Results: Of the 107 amniotic fluid samples tested, nine of 107 (8.4%) were positive by polymerase chain reaction, but only two of these (1.8%) were positive in cell culture; none of the blood samples from infected fetuses were positive for specific anti-varicella zoster virus immunoglobulin M. The outcome of 99 pregnancies was fully documented., Conclusion: The risk of transplacental passage before 24 weeks of pregnancy was 8.4% in our series. The risk of congenital varicella is 3 in 107 (2.8%) and that of isolated postnatal varicella zoster infection is 3 in 78 (3.8%). Polymerase chain reaction is more sensitive than cell culture for the detection of varicella zoster virus in amniotic fluid.