Serological Number for Characterization of Circulating Antibodies.
Ontology highlight
ABSTRACT:
SUBMITTER: Palermo A
PROVIDER: S-EPMC6387039 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
Serological Number for Characterization of Circulating Antibodies.
Palermo Andrea A Nesterov-Mueller Alexander A
International journal of molecular sciences 20190130 3
The dissociation constant of the circulating IgG antibodies is suggested to be proportional to the partial concentrations of these antibodies in blood serum in equilibrium. This coefficient, called serological number, is a dimensionless parameter and may be equal for all antibodies in a serum. Based on the serological number, we derived the equilibrium equation of the humoral immune system which allows estimating the number of different binding motifs in a serum. This equation also allows estima ...[more]
Similar Datasets
Project description:The serological lateral flow immunoassay (LFIA) was used to detect circulating antibodies to skin bacteria. Next-generation sequencing analysis of the skin microbiome revealed a high relative abundance of Cutibacterium acnes but low abundance of Staphylococcus aureus and Corynebacterium aurimucosum on human facial samples. Yet, results from both LFIA and antibody titer quantification in 96-well microplates illustrated antibody titers that were not correspondent, and instead negatively correlated, to their respective abundance with human blood containing higher concentrations of antibodies to both S. aureus and C. aurimucosum than C. acnes. Acne vulgaris develops several unique microbial and cellular features, but its correlation with circulating antibodies to bacteria in the pilosebaceous unit remains unknown. Results here revealed that antibodies to C. acnes and S. aureus were approximately 3-fold higher and 1.5-fold lower, respectively, in acne patients than in healthy subjects. Although the results can be further validated by larger sample sizes, the proof-of-concept study demonstrates a newfound discrepancy between the abundance of skin bacteria and amounts of their corresponding antibodies. And in light of acne-correlated amplified titers of specific anticommensal antibodies, we highlight that profiling these antibodies in the pilosebaceous unit by LFIAs may provide a unique signature for monitoring acne vulgaris.
| S-EPMC8635989 | biostudies-literature
Project description:BackgroundIncreasing evidence indicates that periodontitis contributes to systemic low-grade inflammation. Porphyromonas gingivalis is strongly associated with periodontitis, and antibodies against the bacterium may be used as a serological proxy to account for periodontal status, when studying diseases associated with periodontitis. The aim of the present study is to identify an easily accessible and reliable serological biomarker for determination of periodontal status and oral carriage of the bacterium.MethodsSaliva and serum samples were collected from periodontally healthy controls (n = 27), and patients with periodontitis stage II (n = 12) or stages III or IV (n = 44). Serum levels of immunoglobulin G (IgG) antibodies against intact and fragmented P. gingivalis, recombinant gingipains (RgpA and RgpB), and the bacteria Escherichia coli and Capnocytophaga ochracea as controls were quantified with a multiplex bead-based assay. P. gingivalis was identified in saliva using quantitative polymerase chain reaction (qPCR).ResultsSerum IgG antibodies against P. gingivalis whole bacteria were good indicators of periodontitis (area under the curve [AUC]: 0.75, 95% confidence interval [CI]: 0.64-0.85). The same was observed for levels of antibodies against P. gingivalis fragments (AUC: 0.78, 95% CI: 0.68-0.88). Likewise, levels of antibodies against P. gingivalis whole bacteria or P. gingivalis fragments were good indicators of oral carriage of P. gingivalis (AUC: 0.92, 95% CI: 0.86-0.98 and AUC: 0.96, 95% CI: 0.92-1, respectively). Conversely, antibodies against recombinant RgpA and RgpB were not good indicators of periodontitis or oral carriage of the bacterium. None of the antibody levels differed significantly between stage II and stage III or IV periodontitis.ConclusionSerum IgG antibody levels against heat-inactivated whole P. gingivalis proved to be the preferable biomarker for periodontitis and oral carriage of the bacterium.
| S-EPMC11866731 | biostudies-literature
Project description:Cache Valley virus (CVV) is a mosquito-borne virus in the genus Orthobunyavirus, family Peribunyaviridae. It was first isolated from a Culiseta inorata mosquito in Cache Valley, Utah in 1956 and is known to circulate widely in the Americas. While only a handful of human cases have been reported since its discovery, it is the causative agent of fetal death and severe malformations in livestock. CVV has recently emerged as a potential viral pathogen causing severe disease in humans. Currently, the only serological assay available for diagnostic testing is plaque reduction neutralization test which takes several days to perform and requires biocontainment. To expand diagnostic capacity to detect CVV infections by immunoassays, 12 hybridoma clones secreting anti-CVV murine monoclonal antibodies (MAbs) were developed. All MAbs developed were found to be non-neutralizing and specific to the nucleoprotein of CVV. Cross-reactivity experiments with related orthobunyaviruses revealed several of the MAbs reacted with Tensaw, Fort Sherman, Tlacotalpan, Maguari, Playas, and Potosi viruses. Our data shows that MAbs CVV14, CVV15, CVV17, and CVV18 have high specific reactivity as a detector in an IgM antibody capture test with human sera.
| S-EPMC8812937 | biostudies-literature
Project description:BackgroundHuman cytomegalovirus infection is associated with a variety of pathological conditions including retinitis, pneumonia, hepatitis and encephalitis that may be transmitted congenitally, horizontally and parenterally and occurs both as a primary infection and as reactivation in immunocompromised individuals. Currently, there is a need for improved quantitative serological tests to document seropositivity with high sensitivity and specificity.MethodsHere we investigated whether luciferase immunoprecipitation systems (LIPS) would provide a more quantitative and sensitive method for detecting anti-CMV antibodies. Four protein fragments of immunodominant regions of CMV antigens pp150 and pp65 were generated as Renilla luciferase (Ruc) fusion proteins and used in LIPS with two cohorts of CMV positive and negative sera samples previously tested by ELISA.ResultsAnalysis of the antibody responses to two of these antigen fragments, pp150-d1 and pp150-d2, revealed geometric mean antibody titers in the first cohort that were 100-1000 fold higher in the CMV positive sera compared to the CMV negative samples (p < 0.0001) and infection status exactly matched the ELISA results for the 46 samples of the first cohort (100% sensitivity and 100% specificity). Two additional antigen fragments, pp65-d1 and pp65-d2 also showed robust antibody titers in some CMV-infected sera and yielded 50% and 96% sensitivity, respectively. Analysis of a second cohort of 70 samples using a mixture of the 4 antigens, which simplifies data collection and analysis, yielded values which correlated well with the sum of the values from the 4 separate tests (rs = 0.93, p < 0.00001). While comparison of the LIPS results from this second cohort with ELISA showed 100% sensitivity, LIPS detected six additional CMV positive samples that were not detected by ELISA. Heat map analysis revealed that several of the LIPS positive/ELISA negative samples had positive LIPS immunoreactivity with 3-4 of the CMV antigens.ConclusionThese results suggest that LIPS provides a highly robust and quantitative method for studying anti-CMV antibodies and has the potential to more accurately document CMV infection than standard ELISA.
| S-EPMC2683803 | biostudies-literature
Project description:The aim of this study was to detect antibodies against Paracoccidioides brasiliensis in dogs seropositive and seronegative for leishmaniasis. Sera from 836 dogs (449 positive and 387 negative to leishmaniasis) were analysed by ELISA and the immunodiffusion test using gp43 and exoantigen, respectively. The analysis of the 836 serum samples by ELISA and the immunodiffusion test showed a positivity of 67.8 % and 7.3%, respectively, for P. brasiliensis infection. The dogs positive to leishmaniasis showed a higher reactivity to gp43 (79.9%) and exoantigen (12.7%) than the negative ones (54.0% and 1.0%, respectively). The higher reactivity to P. brasiliensis antigens may be due to cross-reactivity or a co-infection of dogs by Leishmania and P. brasiliensis. The lower correlation (0.187) observed between reactivity to gp43 and Leishmania antigen reinforces the latter hypothesis.
| S-EPMC2780595 | biostudies-other
Project description:BackgroundSerological tests for gambiense human African trypanosomiasis (gHAT) detect antibodies to antigens on the cell surface of bloodstream trypanosomes. As trypanosomes that cause animal African trypanosomiasis (AAT) also express related antigens, we have evaluated two rapid diagnostic tests (RDTs) on cattle in trypanosomiasis endemic and non-endemic regions, to determine whether gHAT serological tests could also be used to screen for AAT.MethodsTwo RDTs, 1G RDT, made with native antigens, and p2G RDT, made with recombinant antigens, were tested on 121 cattle in a trypanosomiasis-free region, and on 312 cattle from a rhodesiense HAT and AAT endemic region. A subset of samples from the endemic region were also tested with two immune trypanolysis (TL) tests. The sensitivity of the tests was estimated by evaluating the result of the RDT on samples that were positive by both microscopy and internal transcribed spacer (ITS) PCR, whilst specificity was the result of the RDT on samples that were negative by ITS PCR and microscopy, and others from the non-endemic region.ResultsThe specificity of the p2G RDT on cattle from the non-endemic region was 97.5% (95% CI: 93.0-99.2%), compared to only 57.9% (95% CI: 48.9-66.3%) for 1G RDT. The specificities of 1G RDT, p2G RDT and TL on endemic control cattle were 14.6% (95% CI: 9.7-21.5%), 22.6% (95% CI: 16.4-30.3%) and 68.3% (95% CI: 59.6-75.9%), respectively. The sensitivities of the tests on trypanosome positive samples were 85.1% (95% CI: 79.1-89.7%), 89.1% (95% CI: 83.7-93.0%) and 59.3% (95% CI: 51.8-66.4%), respectively. Among the same samples, 51.7% were positive by both TL and the 1G RDT.ConclusionsThese serological tests detect cross-reacting antibodies in cattle. The p2G RDT based on recombinant antigens had a high specificity in a non-endemic region, while the 1G RDT had a lower specificity, suggesting cross-reactivity with other pathogens.
| S-EPMC5670715 | biostudies-literature
Project description:Early detection of leprosy is key to reduce the ongoing transmission. Antibodies directed against M. leprae PGL-I represent a useful biomarker for detecting multibacillary (MB) patients. Since efficient leprosy diagnosis requires field-friendly test conditions, we evaluated two rapid lateral flow assays (LFA) for detection of Mycobacterium leprae-specific antibodies: the visual immunogold OnSite Leprosy Ab Rapid test [Gold-LFA] and the quantitative, luminescent up-converting phosphor anti-PGL-I test [UCP-LFA]. Test performance was assessed in independent cohorts originating from three endemic areas. In the Philippine cohort comprising patients with high bacillary indices (BI; average:4,9), 94%(n = 161) of MB patients were identified by UCP-LFA and 78%(n = 133) by Gold-LFA. In the Bangladeshi cohort, including mainly MB patients with low BI (average:1), 41%(n = 14) and 44%(n = 15) were detected by UCP-LFA and Gold-LFA, respectively. In the third cohort of schoolchildren from a leprosy hyperendemic region in Brazil, both tests detected 28%(n = 17) seropositivity. Both rapid tests corresponded well with BI(p < 0.0001), with a fairly higher sensitivity obtained with the UCP-LFA assay. However, due to the spectral character of leprosy, additional, cellular biomarkers are required to detect patients with low BIs. Therefore, the UCP-LFA platform, which allows multiplexing with differential biomarkers, offers more cutting-edge potential for diagnosis across the whole leprosy spectrum.
| S-EPMC5566372 | biostudies-literature
Project description:The impact of COVID-19 is still felt around the world, and more information is needed regarding infection risk, vaccination responses, and the timing of booster vaccinations. We aimed to evaluate the association of vaccination with closely followed, longitudinal antibody titers and COVID-19 infection events. We conducted a natural history study in a convenience cohort in an ambulatory research unit. We measured anti-nucleocapsid and anti-spike antibody levels every 3 months for 1 year and captured weekly reports of medically confirmed COVID-19 infections. We analyzed the association of antibody titers with infection events as well as the association of the decision to receive vaccination with social, medical, and behavioral characteristics. 629 subjects were followed for 1 year, and 82.8% of them were vaccinated. 90 cases of medically confirmed COVID-19 infection were reported. Notable findings from our study include: an association of vaccination choice with social distancing, a qualitatively different anti-spike response in participants receiving the Ad26.COV2.S vaccine compared to those receiving mRNA vaccines, a muted anti-nucleocapsid response in breakthrough infections compared to unvaccinated infections, and the identification of a low antibody titer threshold associated with the risk of breakthrough infections. We conclude that, in a real-life setting, vaccination and social distancing behavior are positively correlated. The observed effect of vaccination in preventing COVID-19 may include both vaccine-mediated protection and the associated more cautious behavior exhibited by vaccinated individuals. In addition, we identified an antibody threshold associated with breakthrough infections in mRNA vaccinees, and this threshold may be used in medical decision-making regarding the timing of booster vaccinations. Therefore, our data may aid in the refinement of vaccination strategies during the COVID-19 pandemic. IMPORTANCE The COVID-19 pandemic continues to impact societies and health care systems worldwide and is continuously evolving. Immunity via vaccination or prior infection is the first and most important line of defense against COVID-19. We still do not have complete information on how vaccination-induced or infection-induced antibody titers change with time or on how this information can be used to guide decisions regarding booster vaccination. In a longitudinal observational study of a cohort of 629 subjects, 82% of breakthrough infections in vaccinees occurred when their anti-spike antibody titers were below 3,000 AU/mL. Our findings suggest that there may be an antibody threshold associated with breakthrough infections and that this threshold could possibly be used to aid decision-making regarding booster vaccinations. In addition, the use of anti-nucleocapsid antibody tiers may significantly underestimate the prevalence of breakthrough infections in vaccinated individuals.
| S-EPMC9603261 | biostudies-literature
Project description:Current serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA-ELISA and dIgA-multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID-19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID-19; (iii) a cross-sectional panel with PCR-confirmed SARS-CoV-2 infection with mild COVID-19 (n = 199) and (iv) pre-COVID-19 samples (n = 200). The dIgA-ELISA and dIgA-MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS-CoV-2 infection. Individuals with mild COVID-19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID-19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID-19 infections are associated with sustained levels of plasma dIgA compared with mild cases.
| S-EPMC10952984 | biostudies-literature
Project description:SARS-CoV-2 virus was first detected in late 2019 and circulated globally, causing COVID-19, which is characterised by sub-clinical to severe disease in humans. Here, we investigate the serological antibody responses to SARS-CoV-2 infection during acute and convalescent infection using a cohort of (i) COVID-19 patients admitted to hospital, (ii) healthy individuals who had experienced 'COVID-19 like-illness', and (iii) a cohort of healthy individuals prior to the emergence of SARS-CoV-2. We compare SARS-CoV-2 specific antibody detection rates from four different serological methods, virus neutralisation test (VNT), ID Screen® SARS-CoV-2-N IgG ELISA, Whole Antigen ELISA, and lentivirus-based SARS-CoV-2 pseudotype virus neutralisation tests (pVNT). All methods were able to detect prior infection with COVID-19, albeit with different relative sensitivities. The VNT and SARS-CoV-2-N ELISA methods showed a strong correlation yet provided increased detection rates when used in combination. A pVNT correlated strongly with SARS-CoV-2 VNT and was able to effectively discriminate SARS-CoV-2 antibody positive and negative serum with the same efficiency as the VNT. Moreover, the pVNT was performed with the same level of discrimination across multiple separate institutions. Therefore, the pVNT is a sensitive, specific, and reproducible lower biosafety level alternative to VNT for detecting SARS-CoV-2 antibodies for diagnostic and research applications. Our data illustrate the potential utility of applying VNT or pVNT and ELISA antibody tests in parallel to enhance the sensitivity of exposure to infection.
| S-EPMC8074400 | biostudies-literature