scholarly journals Analytical and Diagnostic Characteristics of 11 2nd- and 3rd-Generation Immunoenzymatic Methods for the Detection of Antibodies to Citrullinated Proteins

2007 ◽  
Vol 53 (8) ◽  
pp. 1527-1533 ◽  
Author(s):  
Nicola Bizzaro ◽  
Elio Tonutti ◽  
Renato Tozzoli ◽  
Danilo Villalta
Keyword(s):  
Diagnostic Accuracy ◽  
Cyclic Peptides ◽  
Viral Infections ◽  
Roc Curves ◽  
Important Variable ◽  
Serum Samples ◽  
Barr Virus ◽  
Diagnostic Characteristics ◽  
Epstein Barr ◽  
High Concentrations

Abstract Background: Measurement of antibodies to citrullinated peptides or proteins (CP) is a new test for the diagnosis of rheumatoid arthritis (RA). We analyzed the analytical characteristics and diagnostic accuracy of commercially available methods. Methods: We studied 11 commercially available 2nd- and 3rd-generation methods that used various citrullinated antigen substrates: synthetic cyclic peptides, recombinant rat filaggrin, mutated human vimentin, and Epstein–Barr virus- or IgG-derived peptides. We assessed imprecision by measuring samples with low, intermediate, and high concentrations 5 times on each of 5 days. We measured CPs by each of the assays in 100 serum samples from patients with RA and in 202 samples from healthy persons or patients with other autoimmune, viral, or neoplastic diseases. Results: The between-run imprecision (CV) of the methods was between 0.4% and 22%, and the repeatability (within-run imprecision) was 0.5%–19%. The areas under the ROC curves varied between 0.79 (95% CI, 0.72–0.85) and 0.92 (0.88–0.95). At a fixed specificity of 98.5%, the sensitivities ranged from 41% (95% CI, 31%–51%) to 74% (64%–82%). Sensitivities and specificities varied markedly at the manufacturer’s suggested cutoffs. Most false-positive results were recorded in patients with viral infections. The methods that use the original synthetic cyclic CP gave the best and very similar performances, although these methods use different components in their reagent sets (conjugate, type of substrate, dilution, and washing buffers). This finding shows that the antigenic source is the most important variable in determining the diagnostic accuracy of the methods. Conclusions: The analytical imprecision and diagnostic accuracies of commercially available methods for the detection of anti-CP antibodies differ. Careful selection of methods is needed.

scholarly journals Characteristics of three different chemiluminescence assays for testing for SARS-CoV-2 antibodies

2020 ◽  
Author(s):  
Myriam C. Weber ◽  
Martin Risch ◽  
Sarah L. Thiel ◽  
Kirsten Grossmann ◽  
Susanne Nigg ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Roc Curves ◽  
Likelihood Ratios ◽  
Predictive Values ◽  
Barr Virus ◽  
Negative Results ◽  
Assay Performance ◽  
Epstein Barr ◽  
Low Prevalence ◽  
Roche Diagnostics

AbstractSeveral tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multi-group study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 (n=145), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e. healthy blood donors, n=191, and healthcare workers, n=1002). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of Epstein–Barr virus (EBV) (n=9), cytomegalovirus (CMV) (n=7) and endemic common cold coronavirus infections (n=12) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers’ cut-offs, the sensitivities were 90%, 95% confidence interval,[84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8](CMIA) 99.7% [99.3,99,9] (LIA) and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers’ cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers’ cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.

scholarly journals Characteristics of Three Different Chemiluminescence Assays for Testing for SARS-CoV-2 Antibodies

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Myriam C. Weber ◽  
Martin Risch ◽  
Sarah L. Thiel ◽  
Kirsten Grossmann ◽  
Susanne Nigg ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Roc Curves ◽  
Likelihood Ratios ◽  
Predictive Values ◽  
Barr Virus ◽  
Negative Results ◽  
Assay Performance ◽  
Epstein Barr ◽  
Low Prevalence ◽  
Roche Diagnostics

Several tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multigroup study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 ( n = 145 ), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e., healthy blood donors, n = 191 , and healthcare workers, n = 1002 ). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of the Epstein–Barr virus (EBV) ( n = 9 ), cytomegalovirus (CMV) ( n = 7 ), and endemic common-cold coronavirus infections ( n = 12 ) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers’ cut-offs, the sensitivities were 90%, 95% confidence interval [84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8] (CMIA), 99.7% [99.3,99.9] (LIA), and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers’ cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers’ cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.

Acute Pharyngitis: Etiology and Diagnosis

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 949-954
Author(s):  
Alan L. Bisno
Keyword(s):  
Herpes Simplex ◽  
Influenza A ◽  
Epstein Barr Virus ◽  
Viral Infections ◽  
Clinical Manifestations ◽  
Acute Pharyngitis ◽  
Herpesvirus Type ◽  
Barr Virus ◽  
Epstein Barr

Acute pharyngitis may be caused by a wide variety of microbial agents (Table 1). The relative importance of each of these agents varies greatly depending on a number of epidemiologic factors, including age of the patient, season of the year, and geographic locale. Viruses Most cases of acute pharyngitis are viral in etiology and involve the pharynx as well as other portions of the respiratory tract as manifestations of the common cold, influenza, or croup. Examples include the rhinoviruses, coronaviruses, influenza A and B, and the parainfluenza viruses. Certain viral infections causing sore throat may exhibit clinical manifestations that are rather distinctive. Examples include enteroviruses (herpangina due to Coxsackie A), Epstein-Barr virus (infectious mononucleosis), cytomegalovirus (cytomegalovirus mononucleosis), adenovirus (pharyngoconjunctival fever, acute respiratory disease of military recruits), and herpes simplex virus (pharyngitis, gingivitis, and stomatitis). In many instances, however, the illnesses caused by these agents may overlap so broadly with that of streptococcal pharyngitis as to be clinically indistinguishable. Thus, Epstein-Barr virus, adenovirus, and herpes virus may all cause fever, exudative pharyngitis, and cervical adenitis. Several studies have documented the role of primary herpesvirus type 1 infection as a cause of acute pharyngitis in college students.1-4 Herpesvirus type 2 can occasionally cause a similar illness as a consequence of oral-genital sexual contact.5 Although herpesvirus infections may involve the anterior oral cavity (vesicular or ulcerative gingivostomatitis) as well as the posterior pharynx, they do not routinely do so. Only about one-fourth of students with culturally and serologically proven primary herpes simplex type 1 pharyngitis studied by Glezen et al,2 for example, had gingivostomatitis.

scholarly journals Three Severe Cases of Viral Infections with Post-Kidney Transplantation Successfully Confirmed by Polymerase Chain Reaction and Flow Cytometry

2018 ◽  
Vol 8 (3) ◽  
pp. 198-206
Author(s):  
Keita Nakanishi ◽  
Hiroshi Kaito ◽  
Miki Ogi ◽  
Denshi Takai ◽  
Junya Fujimura ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Polymerase Chain Reaction ◽  
Kidney Transplantation ◽  
Viral Infections ◽  
Specific Treatment ◽  
Epstein Barr Virus Infection ◽  
Chain Reaction ◽  
Barr Virus ◽  
Polymerase Chain ◽  
Epstein Barr

Viral infections in patients with post-kidney transplantation are often difficult to diagnose as well as treat. We herein report three cases with severe viral infections after kidney transplantation. All their causative pathogens could be detected promptly by polymerase chain reaction and flow cytometry during the early stages of infection. These examinations would also be of great use to monitor therapeutic responses and disease activity. It is indeed true that no specific treatment is available for most of the viral infections, but we should be aware that some infections, such as Epstein-Barr virus infection, can be treatable with prompt and specific treatment, such as rituximab.

scholarly journals Pancytopenia Secondary to SARS-CoV 2 Infection-A Case Reprt

2021 ◽  
Author(s):  
Neeraj Sharma ◽  
Rajat Shukla ◽  
Rachna Warrier ◽  
Kunal Kumar ◽  
Nalin Singh ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Blood Cells ◽  
Epstein Barr Virus ◽  
Viral Infections ◽  
Parvovirus B19 ◽  
Rare Complication ◽  
Elderly Male ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr

Abstract Pancytopenia is a condition when person has low count of all three types of blood cells causing a triage of anemia, leukopenia and thrombocytopenia. It should not be considered as a disease in itself but rather the sign of a disease that needs to be further evaluated. Among the various causes, viral infections like Human Immunodeficiency Virus, Cytomegalovirus, Epstein-Barr virus and Parvovirus B19 have been implicated. Pancytopenia is a rare complication and not commonly seen in patients with COVID 19 disease. Here, we report a case of pancytopenia in previously immunocompetent elderly male patient with SARS-CoV2 infection.

scholarly journals Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment

2012 ◽  
pp. 305-311 ◽  
Author(s):  
María Lilia Diaz Betancourth ◽  
Julio Cesar Klinger ◽  
Victoria Eugenia Niño
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epstein Barr Virus ◽  
Herpes Virus ◽  
Viral Infections ◽  
Human Herpes ◽  
Barr Virus ◽  
Human Herpes Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr ◽  
Herpès Virus

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immu­nodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lym­phocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diag­nosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health.

scholarly journals The prevalence of the most important viral infections in renal transplant recipients in Serbia

2012 ◽  
Vol 64 (4) ◽  
pp. 1285-1296 ◽  
Author(s):  
Maja Cupic ◽  
Ivana Lazarevic ◽  
Vera Pravica ◽  
Ana Banko ◽  
Danijela Karalic ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Viral Infections ◽  
Opportunistic Infections ◽  
Uv Light ◽  
Molecular Testing ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Chi Square ◽  
Barr Virus ◽  
Epstein Barr

Viruses are the main cause of opportunistic infections after kidney transplantation. The aim of this study was to determine the prevalence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), B. K. virus (BKV) and John Cunningham virus (JCV) infections in renal transplant recipients (RTR). This retrospective study of 112 RTR investigated the presence of CMV, EBV and polyomaviruses DNA in plasma and/or urine by PCR. The visualization of PCR products was performed by electrophoresis on 2% agarose gel stained with ethidium bromide and photographed under a UV light. The chi-square test was used for statistical analysis. CMV DNA was detected in 14/112 (12.5%), EBV DNA in 4/49 (8.16%), BKV DNA in 10/31 (32.26%) and JCV DNA in 3/31 (9.68%) RTR. These results show that CMV infection is more often present in RTR compared to other investigated viral infections. In the light of these results, molecular testing could be useful in identifying recipients at high risk of symptomatic post-transplant viral infection.

scholarly journals Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAE

2021 ◽  
Author(s):  
Isobel C. Mouat ◽  
Jessica R. Allanach ◽  
Vina Fan ◽  
Anna M. Girard ◽  
Iryna Shanina ◽  
...  
Keyword(s):  
B Cells ◽  
Viral Infection ◽  
Viral Infections ◽  
Autoimmune Encephalomyelitis ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latent Viral Infection ◽  
Epstein Barr ◽  
Gammaherpesvirus 68 ◽  
Experimental Autoimmune

While age-associated B cells (ABCs) are known to expand and persist following viral infection and during autoimmunity, their interactions are yet to be studied together in these contexts. Epstein-Barr virus (EBV) infection has long been implicated in multiple sclerosis (MS), and it is not known whether ABCs could play a role in mediating viral contribution to autoimmunity. Here, we show that the circulating ABC population is expanded in people with MS and that EBV infection and MS status differentially impact the circulating ABC phenotype. We then directly compared ABCs during viral infection and autoimmunity using mouse models of EBV, gammaherpesvirus 68 (γHV68), and MS, experimental autoimmune encephalomyelitis (EAE). We observed that splenic ABCs are expanded in a sex-biased manner during both latent virus infection and EAE, and each event drives the ABC population to opposing phenotypes. We have previously shown that latent γHV68 infection exacerbates EAE and here we show that mice lacking ABCs fail to display γHV68-enhanced disease. Collectively, these findings indicate that latent viral infection and central nervous system autoimmunity differentially impact the ABC population and suggests that viral infections such as EBV prime ABCs to contribute pathogenically in MS.

Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1165-1171 ◽  
Author(s):  
Servi J. C. Stevens ◽  
Erik A. M. Verschuuren ◽  
Inge Pronk ◽  
Wim van der Bij ◽  
Martin C. Harmsen ◽  
...  
Keyword(s):  
Whole Blood ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Serum Samples ◽  
Barr Virus ◽  
Load Monitoring ◽  
Risk Patients ◽  
Posttransplant Lymphoproliferative Disease ◽  
Ebv Dna ◽  
Epstein Barr

Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)–associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cut-off value (P < .0001) despite heavy immune suppression and cytomegalovirus (CMV)-related disease. These findings illustrate the clinical importance of frequent EBV DNA load monitoring in LTx recipients. The increased EBV DNA loads in PTLD patients were restricted to the cellular blood compartment, as parallel serum samples were all below cut-off value, which indicates absence of lytic viral replication. EBV+ cells in PTLD patients have a very short doubling time, which can be as low as 56 hours, thereby creating the need for high screening frequency in high-risk patients. Furthermore, it is shown that EBV and CMV can reactivate independently in LTx recipients and that EBV DNA load monitoring may be useful in discriminating PTLD from rejection.

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