scholarly journals Serological signatures of SARS-CoV-2 infection: Implications for antibody-based diagnostics

2020 ◽  
Author(s):  
Jason Rosado ◽  
Stéphane Pelleau ◽  
Charlotte Cockram ◽  
Sarah Hélène Merkling ◽  
Narimane Nekkab ◽  
...  
Keyword(s):  
Population Level ◽  
Classification Performance ◽  
Negative Control ◽  
Antibody Responses ◽  
Serum Samples ◽  
Igg Antibody ◽  
Low Transmission ◽  
Control Serum ◽  
Challenges And Opportunities ◽  
Serological Diagnostics

AbstractBackgroundInfection with SARS-CoV-2 induces an antibody response targeting multiple antigens that changes over time. This complexity presents challenges and opportunities for serological diagnostics.MethodsA multiplex serological assay was developed to measure IgG and IgM antibody responses to seven SARS-CoV-2 spike or nucleoprotein antigens, two antigens for the nucleoproteins of the 229E and NL63 seasonal coronaviruses, and three non-coronavirus antigens. Antibodies were measured in serum samples from patients in French hospitals with RT-qPCR confirmed SARS-CoV-2 infection (n = 259), and negative control serum samples collected before the start of the SARS-CoV-2 epidemic (n = 335). A random forests algorithm was trained with the multiplex data to classify individuals with previous SARS-CoV-2 infection. A mathematical model of antibody kinetics informed by prior information from other coronaviruses was used to estimate time-varying antibody responses and assess the potential sensitivity and classification performance of serological diagnostics during the first year following symptom onset. A statistical estimator is presented that can provide estimates of seroprevalence in very low transmission settings.ResultsIgG antibody responses to trimeric Spike protein identified individuals with previous RT-qPCR confirmed SARS-CoV-2 infection with 91.6% sensitivity (95% confidence interval (CI); 87.5%, 94.5%) and 99.1% specificity (95% CI; 97.4%, 99.7%). Using a serological signature of IgG and IgM to multiple antigens, it was possible to identify infected individuals with 98.8% sensitivity (95% CI; 96.5%, 99.6%) and 99.3% specificity (95% CI; 97.6%, 99.8%). Informed by prior data from other coronaviruses, we estimate that one year following infection a monoplex assay with optimal anti-Stri IgG cutoff has 88.7% sensitivity (95% CI: 63.4%, 97.4%), and that a multiplex assay can increase sensitivity to 96.4% (95% CI: 80.9%, 100.0%). When applied to population-level serological surveys, statistical analysis of multiplex data allows estimation of seroprevalence levels less than 1%, below the false positivity rate of many other assays.ConclusionSerological signatures based on antibody responses to multiple antigens can provide accurate and robust serological classification of individuals with previous SARS-CoV-2 infection. This provides potential solutions to two pressing challenges for SARS-CoV-2 serological surveillance: classifying individuals who were infected greater than six months ago, and measuring seroprevalence in serological surveys in very low transmission settings.

scholarly journals Longitudinal Analysis of Cryptosporidium Species-Specific Immunoglobulin G Antibody Responses in Peruvian Children

2006 ◽  
Vol 13 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Jeffrey W. Priest ◽  
Caryn Bern ◽  
Lihua Xiao ◽  
Jacquelin M. Roberts ◽  
James P. Kwon ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Antibody Responses ◽  
Health Interventions ◽  
Older Children ◽  
Serum Samples ◽  
Igg Antibody ◽  
Specific Immunoglobulin ◽  
Antibody Assays ◽  
Species Specific ◽  
Antibody Levels

ABSTRACT Cryptosporidium species are ubiquitous in the environment and are frequently detected in the stools of children who live where sanitation conditions are poor. To better characterize the immune response to these parasites, we monitored immunoglobulin G (IgG) antibody levels in a cohort of children from Lima, Peru. Two new enzyme-linked immunosorbent assays based on the C. parvum (bovine, subtype IIa) Iowa strain 17-kDa and 27-kDa antigens were used to measure IgG antibody levels in longitudinal serum samples. Antibody responses were detected during infections with C. parvum, C. felis, and C. meleagridis and with four different subtypes of C. hominis. We also noted that the magnitude of the antibody response was related to the number of previous infections and that older children generally had higher levels of antibodies to the two C. parvum antigens. Antibody responses were not associated with infections with either Cyclospora sp. or Giardia sp. We believe the antibody assays will be important tools for monitoring the success of future public health interventions.

scholarly journals Dark Immunofluorescence: Correlation with Serum Immunoglobulin Abnormalities

2006 ◽  
Vol 13 (11) ◽  
pp. 1294-1295
Author(s):  
J. List ◽  
M. S. Buckland ◽  
B. Thobhani ◽  
C. J. Sheed ◽  
J. C. Mann ◽  
...  
Keyword(s):  
Indirect Immunofluorescence ◽  
Retrospective Review ◽  
Negative Control ◽  
Serum Immunoglobulin ◽  
Serum Samples ◽  
Serum Immunoglobulins ◽  
Control Serum ◽  
Negative Control Serum

ABSTRACT Occasional serum samples (<0.5%) tested by indirect immunofluorescence showed less fluorescence than did negative-control serum. A retrospective review of these patients' serum immunoglobulins revealed a high percentage of abnormalities (71%, versus 22% of controls). We suggest that this observation should be reported when seen and that the clinician should be alerted to an association with immunoglobulin abnormalities.

scholarly journals Serological Diagnosis of Brucella Infections in Odontocetes

2009 ◽  
Vol 16 (6) ◽  
pp. 906-915 ◽  
Author(s):  
Gabriela Hernández-Mora ◽  
Charles A. Manire ◽  
Rocío González-Barrientos ◽  
Elías Barquero-Calvo ◽  
Caterina Guzmán-Verri ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Brucella Melitensis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dot Blot ◽  
Serum Samples ◽  
Igg Antibody ◽  
Serological Tests ◽  
Diagnostic Potential ◽  
Control Serum ◽  
History Of

ABSTRACT Brucella ceti causes disease in Odontoceti. The absence of control serum collections and the diversity of cetaceans have hampered the standardization of serological tests for the diagnosis of cetacean brucellosis. Without a “gold” standard for sensitivity and specificity determination, an alternative approach was followed. We designed an indirect enzyme-linked immunosorbent assay (iELISA) that recognizes immunoglobulins G (IgGs) from 17 odontocete species as a single group. For the standardization, we used Brucella melitensis and Brucella abortus lipopolysaccharides, serum samples from seven resident odontocetes with no history of infectious disease displaying negative rose bengal test (RBT) reactions, and serum samples from seven dolphins infected with B. ceti. We compared the performance of the iELISA with those of the protein G ELISA (gELISA), the competitive ELISA (cELISA), and the immunofluorescence (IF) and dot blot (DB) tests, using 179 odontocete serum samples and RBT as the reference. The diagnostic potential based on sensitivity and specificity of the iELISA was superior to that of gELISA and cELISA. The correlation and agreement between the iELISA and the gELISA were relatively good (R i/g 2 = 0.65 and κi/g = 0.66, respectively), while the correlation and agreement of these two ELISAs with cELISA were low (R i/c 2 = 0.46, R g/c 2 = 0.37 and κi/c = 0.62, κg/c = 0.42). In spite of using the same anti-odontocete IgG antibody, the iELISA was more specific than were the IF and DB tests. An association between high antibody titers and the presence of neurological symptoms in dolphins was observed. The prediction is that iELISA based on broadly cross-reacting anti-dolphin IgG antibody would be a reliable test for the diagnosis of brucellosis in odontocetes, including families not covered in this study.

scholarly journals Natural Autoimmunity to the Thyroid Hormone Monocarboxylate Transporters MCT8 and MCT10

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 496
Author(s):  
Theresa Porst ◽  
Jörg Johannes ◽  
Hans Gluschke ◽  
Richard Köhler ◽  
Sebastian Mehl ◽  
...  
Keyword(s):  
Cell Culture ◽  
Thyroid Hormone ◽  
Thyroid Disease ◽  
Biological Effects ◽  
Negative Control ◽  
Monocarboxylate Transporters ◽  
Healthy Controls ◽  
Serum Samples ◽  
Control Serum ◽  
Overweight Adolescents

The monocarboxylate transporters 8 (MCT8) and 10 (MCT10) are important for thyroid hormone (TH) uptake and signaling. Reduced TH activity is associated with impaired development, weight gain and discomfort. We hypothesized that autoantibodies (aAb) to MCT8 or MCT10 are prevalent in thyroid disease and obesity. Analytical tests for MCT8-aAb and MCT10-aAb were developed and characterized with commercial antiserum. Serum samples from healthy controls, thyroid patients and young overweight subjects were analyzed, and prevalence of the aAb was compared. MCT8-aAb were additionally tested for biological effects on thyroid hormone uptake in cell culture. Positive MCT8-aAb and MCT10-aAb were detected in all three clinical cohorts analyzed. MCT8-aAb were most prevalent in thyroid patients (11.9%) as compared to healthy controls (3.8%) and overweight adolescents (4.2%). MCT8-aAb positive serum reduced T4 uptake in cell culture in comparison to MCT8-aAb negative control serum. Prevalence of MCT10-aAb was highest in the group of thyroid patients as compared to healthy subjects or overweight adolescents (9.0% versus 4.5% and 6.3%, respectively). We conclude that MCT8 and MCT10 represent autoantigens in humans, and that MCT8-aAb may interfere with regular TH uptake and signaling. The increased prevalence of MCT8-aAb and MCT10-aAb in thyroid disease suggests that their presence may be of pathophysiological relevance. This hypothesis deserves an analysis in large prospective studies.

scholarly journals SARS-CoV-2 IgG antibody responses in rt-PCR positive cases: first report from India

2020 ◽  
Author(s):  
Girish Chandra Dash ◽  
Debaprasad Parai ◽  
Hari Ram Choudhary ◽  
Annalisha Peter ◽  
Usha Kiran Rout ◽  
...  
Keyword(s):  
Antibody Response ◽  
Infected Individual ◽  
Antibody Responses ◽  
Rt Pcr ◽  
Serum Samples ◽  
Igg Antibody ◽  
Ct Value ◽  
Significant Difference ◽  
The Mean ◽  
The Relationship

AbstractThe SARS-CoV-2 antibody responses remain poorly understood and the clinical utility of serological testing is still unclear. As it is thought to confer some degree of immunity, this study is carried out to know the relationship between demographics and ct value of confirmed rt-PCR patients. A total of 384 serum samples were collected between 4-6 weeks after confirmed SARS-CoV-2 infection. IgG positivity was found to be 80.2% (95% CI, 76.2 – 84.2). The IgG positivity increased with the decrease in the ct value, with highest of 87.6% positivity in individuals with <20 ct value. The mean (± SD) ct value of IgG positives and og IgG negatives was 23.34 (± 6.09) and 26.72 (± 7.031) respectively. There was no significant difference found between the demographic characteristics such as age, sex, symptoms and antibody response. The current study is first of its kind wherein we have assessed the correlation of ct of RT-PCR with development of IgG against SARS-CoV-2. Our study showed that although Ct value might not have any relation with severity of the diseases but is associated with the antibody response among the SARS-CoV-2 infected individual.

scholarly journals Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Falconi-Agapito ◽  
Karen Kerkhof ◽  
Xiomara Merino ◽  
Johan Michiels ◽  
Marjan Van Esbroeck ◽  
...  
Keyword(s):  
Antibody Response ◽  
Acute Phase ◽  
Dengue Infection ◽  
Public Health Problem ◽  
Antibody Responses ◽  
Major Public Health Problem ◽  
Serum Samples ◽  
Igg Antibody ◽  
Time Points ◽  
Secondary Infections

Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longitudinally across four time points over the period of six months in Peru and over two time points in travelers. We show that epitopes eliciting the strongest flavivirus cross-reactive antibodies, in both primary and secondary infections were concentrated in the capsid, E, NS1, NS3 and NS5 proteins. The IgG antibody responses against NS1 and NS3 followed a rise-and-fall pattern, with peak titers between two to four weeks after onset of illness. The response to the E and NS5 proteins increased rapidly in the acute phase and was maintained at stable levels until at least 6 months after illness. A more scattered IgM antibody reactivity across the viral proteome was observed in the acute phase of the disease and that persisted through the 6-month window. The magnitude, breadth (i.e. number of unique epitopes targeted) and depth (i.e. number of epitope variants recognized) of the IgG response was higher in secondary infections compared to primary infections. For IgM antibodies, the magnitude of the response was higher in primary infected individuals whereas the breadth and depth of the response was lower in this group compared with the endemic subjects. Finally, through this arboviral proteome-wide epitope mapping, we were able to identify IgM and IgG dengue-specific epitopes which can be useful serological markers for dengue diagnosis and serostatus determination.

scholarly journals IgG antibody responses are preferential compared to IgM for use as serological markers for detecting recent exposure to Plasmodium vivax infection

2020 ◽  
Author(s):  
Rhea Longley ◽  
Michael White ◽  
Jessica Brewster ◽  
Zoe Liu ◽  
Caitlin Bourke ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Classification Performance ◽  
Antibody Responses ◽  
Plasma Samples ◽  
Serological Markers ◽  
Igg Antibody ◽  
Recent Exposure ◽  
Observational Cohort

To achieve malaria elimination, new tools are required to explicitly target Plasmodium vivax. Recently, a novel panel of P. vivax proteins were identified and validated as serological markers for detecting recent exposure to P. vivax within the last 9 months. In order to improve the sensitivity and specificity of these markers, IgM in addition to IgG antibody responses were assessed to a down-selected panel of 20 P. vivax proteins. IgM was tested using archival plasma samples from observational cohort studies conducted in malaria-endemic regions of Thailand and Brazil. IgM responses to these proteins generally had poorer classification performance than IgG.

scholarly journals Use of Antibody Avidity Assays for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus Infection

2007 ◽  
Vol 14 (11) ◽  
pp. 1433-1436 ◽  
Author(s):  
K. H. Chan ◽  
K. Sonnenberg ◽  
M. Niedrig ◽  
S. Y. Lam ◽  
C. M. Pang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Responses ◽  
High Avidity ◽  
Serum Samples ◽  
Igg Antibody ◽  
Antibody Avidity ◽  
Indirect Immunofluorescent Assay ◽  
Serial Serum ◽  
Coronavirus Infection ◽  
Indirect Immunofluorescent

ABSTRACT An indirect immunofluorescent assay (Euroimmun AG, Luebeck, Germany) was used to investigate the avidity of immunoglobulin G (IgG), IgM, IgA, and total Ig (IgGAM) antibody responses to severe acute respiratory syndrome coronavirus (SARS CoV) infections. Serial serum samples from eight patients collected during the first, third, and ninth months after the onset of infection were evaluated. It was found that low-avidity IgG antibodies were detected in 15/15 (100%), 1/5 (20%), and 0/8 (0%) serum samples collected during the first, third, and ninth months after the onset of symptoms, respectively. Low-avidity antibodies of IgA and IgM subclasses were detected in 14/14 (100%) and 3/14 (21%) serum samples, respectively, collected in the first month after the onset of infection. However, IgA antibodies remained low in avidity in a proportion of patients even during late convalescence. As a consequence, IgG antibody avidity assays gave better discrimination between acute-phase and late-convalescent-phase serum samples than IgM, IgA, or IgGAM assays. In two of these patients, sequential serum samples were also tested for IgG avidity against human CoV strains OC43 and 229E in parallel. While SARS CoV infections induced an anamnestic IgG antibody response to the 229E and OC43 viruses, these cross-reactive antibodies remained of high avidity from early (the first month) postinfection. The results showed that assays to detect low-avidity antibody may be useful for discriminating early from late antibody responses and also for distinguishing anamnestic cross-reactive antibody responses from primary specific responses. This may be useful in some clinical situations.

scholarly journals IgG antibody responses are preferential compared to IgM for use as serological markers for detecting recent exposure to Plasmodium vivax infection

2021 ◽  
Author(s):  
Rhea J Longley ◽  
Michael T White ◽  
Jessica Brewster ◽  
Zoe S J Liu ◽  
Caitlin Bourke ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Classification Performance ◽  
Antibody Responses ◽  
Plasma Samples ◽  
Serological Markers ◽  
Igg Antibody ◽  
Recent Exposure ◽  
Observational Cohort

Abstract To achieve malaria elimination, new tools are required to explicitly target Plasmodium vivax. Recently, a novel panel of P. vivax proteins were identified and validated as serological markers for detecting recent exposure to P. vivax within the last 9 months. In order to improve the sensitivity and specificity of these markers, IgM in addition to IgG antibody responses were assessed to a down-selected panel of 20 P. vivax proteins. IgM was tested using archival plasma samples from observational cohort studies conducted in malaria-endemic regions of Thailand and Brazil. IgM responses to these proteins generally had poorer classification performance than IgG.

scholarly journals Evaluation of a Western Blot Test in an Outbreak of Acute Pulmonary Histoplasmosis

1999 ◽  
Vol 6 (1) ◽  
pp. 20-23 ◽  
Author(s):  
Claudia V. Pizzini ◽  
Rosely M. Zancopé-Oliveira ◽  
Errol Reiss ◽  
Rana Hajjeh ◽  
Leo Kaufman ◽  
...  
Keyword(s):  
Western Blot ◽  
Acute Phase ◽  
Periodate Oxidation ◽  
Negative Control ◽  
Acute Stage ◽  
Serum Samples ◽  
Specific Test ◽  
Carbohydrate Epitopes ◽  
Pulmonary Histoplasmosis ◽  
Control Serum

ABSTRACT A western blot (WB) test was evaluated for detection of antibodies against native glycosylated and chemically deglycosylated M and H antigens of Histoplasma capsulatum in serum obtained from patients during the acute phase of pulmonary histoplasmosis that occurred during an outbreak. Of 275 serum samples tested by immunodiffusion and complement fixation (CF) samples from 40 patients affected during this outbreak and from 37 negative controls were tested by WB test. A group of patients whose sera were negative for CF antibodies and precipitins early in the acute stage of histoplasmosis but who all seroconverted during convalescence 6 weeks later were tested with the WB test. Antibodies against untreated H and M antigens were detected at a 1:100 dilution by WB test in 45% of the 20 acute-phase serum samples and in all 20 of the convalescent-phase specimens. The WB test’s sensitivity for acute-phase specimens increased to 90% (18 of 20 specimens) when H and M antigens were treated by periodate oxidation to inactivate susceptible carbohydrate epitopes. When native glycosylated antigens were used in the WB test, positive reactions were observed in negative control serum specimens (3 of 37 specimens; 8%) and in serum specimens obtained from asymptomatic persons screened as part of the outbreak investigation (13 of 20 specimens; 65%). These positive reactions were also attributed to glycosidic epitopes since the specificity of the WB test increased from 78 to 100% when periodate-treated H and M antigens were used. WB test with deglycosylated H and M antigens of histoplasmin provides a rapid, sensitive, and specific test to diagnose acute pulmonary histoplasmosis before precipitins can be detected.

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