SARS-CoV-2 SEROLOGICAL CROSS-REACTIVITY TESTING IN BRAZILIAN BLOOD DONORS, OCTOBER-DECEMBER, 2019

AbstractTrefoil peptides (TFF1, TFF2 and TFF3) are 7–12 kDa molecules, secreted by mucin-producing epithelial cells. Increased serum concentrations have been reported in a number of pathological conditions, which warrants the need for validated commercially available assays.We validated commercial assays for TFF1-3 and compared results obtained with our in-house assays, using serum from blood donors.Level of detection was: ≤0.008 nmol/L. Measuring ranges were: 0.032–0.51 (TFF1), 0.038–0.76 (TFF2) and 0.019–0.15 (TFF3) nmol/L. Imprecision (CV), judged from the measurement of serum pools in two levels, was below 9% (TFF2 and TFF3) but up to 18% (mean 0.41 nmol/L) for TFF1. No cross reactivity between the TFFs (concentrations >100 nmol/L) was observed. The 95% non-parametric reference intervals were: <0.0032–0.53 (TFF1), 0.099–1.4 (TFF2) and 0.086–0.87 (TFF3) nmol/L. Comparing commercial to in-house assays (n=132), showed biases explained by differences in the calibrators (TFF1 and TFF2). A number of samples showed markedly different results.The commercial assays for TFF2 and TFF3 are acceptable for use on serum samples, while the TFF1 assay revealed a poor imprecision and a too narrow measuring range. Results obtained with the commercial and the in-house assays differed, partly because of differences in the calibrators employed.

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Immune Responses to Bile-Tolerant Helicobacter Species in Patients with Chronic Liver Diseases, a Randomized Population Group, and Healthy Blood Donors

Clinical and Vaccine Immunology ◽

10.1128/cdli.9.6.1160-1164.2002 ◽

2002 ◽

Vol 9 (6) ◽

pp. 1160-1164 ◽

Cited By ~ 11

Author(s):

Olga Ananieva ◽

Ingrid Nilsson ◽

Tamara Vorobjova ◽

Raivo Uibo ◽

Torkel Wadström

Keyword(s):

Cell Surface ◽

Liver Diseases ◽

Blood Donors ◽

Population Group ◽

Cross Reactivity ◽

Chronic Liver ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Chronic Liver Diseases ◽

H Pylori

ABSTRACT Bile-tolerant Helicobacter species such as Helicobacter pullorum, Helicobacter bilis, and Helicobacter hepaticus are associated with hepatic disorders in animals and may be involved in the pathogenesis of chronic liver diseases (CLD) in humans. Antibody responses to cell surface proteins of H. pullorum, H. bilis, and H. hepaticus in serum samples from patients with CLD, a randomized population group, and healthy blood donors were evaluated by using enzyme linked immunosorbent assay (ELISA). The results were compared with the antibody responses to Helicobacter pylori. For analysis of a possible cross-reactivity between bile-tolerant Helicobacter species and H. pylori, sera from a subpopulation of each group were absorbed with a whole-cell extract of H. pylori and retested by ELISA. Results before absorption showed that the mean value of the ELISA units for H. pullorum was significantly higher in patients with CLD than in healthy blood donors (P = 0.01). Antibody reactivity to cell surface protein of H. hepaticus was also significantly higher in the CLD patients than in the healthy blood donors and the population group (P = 0.005 and P = 0.002, respectively). Following the absorption, antibody responses to H. pullorum decreased significantly in all three groups (P = 0.0001 for CLD patients, P = 0.0005 for the population group, and P < 0.0001 for the blood donors), indicating that cross-reactivity between H. pylori and other Helicobacter spp. occurs. The antibody responses to H. hepaticus and H. bilis in CLD patients remained high following absorption experiments compared to ELISA results before absorption. The significance of this finding requires further investigations.

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Evaluation of eight commercial Zika virus IgM and IgG serology assays for diagnostics and research

PLoS ONE ◽

10.1371/journal.pone.0244601 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244601

Author(s):

Swee Ling Low ◽

Yee Sin Leo ◽

Yee Ling Lai ◽

Sally Lam ◽

Hwee Huang Tan ◽

...

Keyword(s):

Zika Virus ◽

Blood Donors ◽

Cross Reactivity ◽

Public Health Emergency ◽

Test Interpretation ◽

Test Sensitivity ◽

Endemic Setting ◽

Igm Elisa ◽

Test Specificity ◽

High Test

Several commercial Zika virus (ZIKV) serology assays have been developed since the recognition of ZIKV outbreaks as a Public Health Emergency of International Concern in 2016. However, test interpretation for ZIKV serology can be challenging due to antibody cross-reactivity with other flaviviruses like dengue virus (DENV). Therefore, we sought to evaluate the performance of eight commercially available ZIKV IgM and IgG assays across three testing platforms, namely, immunochromatographic tests (ICT), ELISAs and immunofluorescence tests (IIFT). The test panel comprised of 278 samples, including acute and convalescent sera or plasma from ZIKV-confirmed, DENV-confirmed, non-ZIKV and non-DENV patients, and residual sera from healthy blood donors. The ZIKV IgM and IgG serology assays yielded higher test sensitivities of 23.5% - 97.1% among ZIKV convalescent samples as compared to 5.6% - 27.8% among ZIKV acute samples; the test specificities were 63.3% - 100% among acute and convalescent DENV, non-DENV samples. Among the ELISAs and IIFTs, the Diapro ZIKV IgM ELISA demonstrated high test sensitivity (96%) and specificity (80%) when tested on early convalescent samples, while the Euroimmun ZIKV IgG ELISA yielded the highest test specificity of 97% - 100% on samples from non-ZIKV patients and healthy blood donors. For rapid ICTs, the LumiQuick IgM rapid ICT yielded low test sensitivity, suggesting its limited utility. We showed that commercial ZIKV IgM and IgG serology assays have differing test performances, with some having moderate to high test sensitivities and specificities when used in a dengue endemic setting, although there were limitations in IgG serology.

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Antiidiotypic IgG crossreactive with Rh alloantibodies in red cell autoimmunity

Blood ◽

10.1182/blood.v70.3.710.710 ◽

1987 ◽

Vol 70 (3) ◽

pp. 710-715 ◽

Cited By ~ 8

Author(s):

SP Masouredis ◽

MJ Branks ◽

EJ Victoria

Keyword(s):

Hemolytic Anemia ◽

Immune Regulation ◽

Autoimmune Hemolytic Anemia ◽

Blood Donors ◽

Cross Reactivity ◽

Normal Blood ◽

Red Cell

Abstract IgG autoantibodies eluted from RBCs of antiglobulin positive normal blood donors contained at least two antibody populations, an IgG autoantibody (Ab 1), and an IgG population (Ab 2) that agglutinated RBCs coated with some Rh(D) alloantibodies. Eight of 24 autoantibody eluates tested agglutinated 3 of 10 anti-Rh(D) sensitized RBCs. The agglutinating activity was inhibited specifically by preincubation of the autoantibody eluate with the reactive anti-D. The reaction did not require the Fc domain of the anti-Rh(D), since autoantibody eluates agglutinated RBCs coated with F(ab')2 prepared from the reactive anti-D sera. These findings indicate that the RBCs of some antiglobulin- positive blood donors contain an immunoglobulin auto-antiidiotype (Ab 2) against the RBC autoantibody (Ab 1) which is demonstrable through its cross-reactivity with selected Rh(D) alloantibodies. Identification of auto-antiidiotypes in RBC autoimmunity lends support to the idiotype- antiidiotype network hypothesis of immune regulation and is consistent with the bizarre and complex serology of autoimmune hemolytic anemia. The absence of clinical hemolysis in antiglobulin-positive normal blood donors suggests that immunoglobulin idiotype-antiidiotype interactions may play a role in modulating the effects of RBC autoimmunity.

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Development and validation of the Elecsys Anti-SARS-CoV-2 immunoassay as a highly specific tool for determining past exposure to SARS-CoV-2

10.1101/2020.06.16.20132803 ◽

2020 ◽

Cited By ~ 1

Author(s):

Peter Muench ◽

Simon Jochum ◽

Verena Wenderoth ◽

Beatus Ofenloch-Haehnle ◽

Michael Hombach ◽

...

Keyword(s):

Clinical Study ◽

Blood Donors ◽

Diagnostic Testing ◽

Ethics Committee ◽

Cross Reactivity ◽

Data Availability ◽

Ethical Guidelines ◽

Link Type ◽

Wide Range ◽

Roche Diagnostics

AbstractBackgroundThe Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide an accurate and reliable method for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the sensitivity, specificity, and cross-reactivity of the Elecsys Anti-SARS-CoV-2 immunoassay.MethodsThe performance of the Elecsys Anti-SARS-CoV-2 immunoassay was assessed at Roche Diagnostics (Penzberg, Germany). Sensitivity was evaluated using anonymised residual frozen samples from patients who had previously tested positive for SARS-CoV-2 infection by polymerase chain reaction (PCR); one or more consecutive samples were collected from patients at various timepoints after PCR confirmation. Specificity was evaluated using anonymised unselected residual frozen samples from routine diagnostic testing or from blood donors; all samples were collected before December 2019 and thus deemed negative for SARS-CoV-2-specific antibodies. Cross-reactivity was evaluated using anonymised frozen samples containing a wide range of potentially cross-reacting analytes, which were purchased from commercial vendors. For sensitivity and specificity, point estimates and 95% confidence intervals (CIs) were calculated.ResultsSensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in 496 samples from 102 patients with prior PCR-confirmed SARS-CoV-2 infection was 99.5% (95% CI 97.0–100.0) at ≥14 days after PCR confirmation. Overall specificity in 10,453 samples from routine diagnostic testing (n = 6305) and blood donors (n = 4148) was 99.80% (95% CI 99.69–99.88). Only 4/752 samples containing potential cross-reacting analytes were reactive with the Elecsys Anti-SARS-CoV-2 immunoassay, resulting in an overall specificity in this cohort of 99.5% (95% CI 98.6–99.9).ConclusionThe Elecsys Anti-SARS-CoV-2 immunoassay demonstrated a sensitivity of 99.5% at ≥14 days after PCR confirmation and a very high specificity of 99.80%. Our findings support the use of the Elecsys Anti-SARS-CoV-2 immunoassay as a tool for the identification of past SARS-CoV-2 infection, including in populations with a low disease prevalence.Required information for submission systemEthical guidelinesThe study was conducted in accordance with applicable regulations, including relevant European Union directives and regulations, and the principles of the Declaration of Helsinki. All samples, excluding the specimens that were provided by commercial sample vendors, were transferred to Roche following anonymisation. For studies with anonymised leftover specimens, no ethics committee vote is required. A statement was obtained from the Ethics Committee of the Landesä rztekammer Bayern confirming that there are no objections against the transfer and the coherent use of the anonymised leftover samples.Research reporting guidelinesPlease see separate STARD checklistData availability statementQualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roche’s criteria for eligible studies are available here: https://vivli.org/members/ourmembers/. For further details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm.

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EVALUATION OF CROSS REACTIVITY BETWEEN Trypanosoma cruzi AND Leishmania infantum IN SEROLOGICALLY INELIGIBLE BLOOD DONORS DUE TO CHAGAS DISEASE

Revista de Patologia Tropical / Journal of Tropical Pathology ◽

10.5216/rpt.v46i1.46298 ◽

2017 ◽

Vol 46 (1) ◽

pp. 113 ◽

Cited By ~ 1

Author(s):

Márcia Maria Ferreira-Silva ◽

Silvio Fernando Guimarães Carvalho ◽

Jamille Fernandes Lula ◽

Leandro De Freitas Teles ◽

Fernando Valadares Basques ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Leishmania Infantum ◽

Blood Donors ◽

Cross Reactivity

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Establishment of an Alphavirus-Specific Neutralization Assay to Distinguish Infections with Different Members of the Semliki Forest complex

Viruses ◽

10.3390/v11010082 ◽

2019 ◽

Vol 11 (1) ◽

pp. 82 ◽

Cited By ~ 7

Author(s):

Lisa Henss ◽

Constanze Yue ◽

Joshua Kandler ◽

Helen M. Faddy ◽

Graham Simmons ◽

...

Keyword(s):

Blood Donors ◽

Febrile Illness ◽

Neutralization Assay ◽

Cross Reactivity ◽

Epidemiological Surveillance ◽

Ross River Virus ◽

Mosquito Vectors ◽

The Indian Ocean ◽

Specific Reactivity ◽

Mayaro Virus

Background: Alphaviruses are transmitted by arthropod vectors and can be found worldwide. Alphaviruses of the Semliki Forest complex such as chikungunya virus (CHIKV), Mayaro virus (MAYV) or Ross River virus (RRV) cause acute febrile illness and long-lasting arthralgia in humans, which cannot be clinically discriminated from a dengue virus or Zika virus infection. Alphaviruses utilize a diverse array of mosquito vectors for transmission and spread. For instance, adaptation of CHIKV to transmission by Aedes albopictus has increased its spread and resulted in large outbreaks in the Indian Ocean islands. For many alphaviruses commercial diagnostic tests are not available or show cross-reactivity among alphaviruses. Climate change and globalization will increase the spread of alphaviruses and monitoring of infections is necessary and requires virus-specific methods. Method: We established an alphavirus neutralization assay in a 384-well format by using pseudotyped lentiviral vectors. Results: MAYV-specific reactivity could be discriminated from CHIKV reactivity. Human plasma from blood donors infected with RRV could be clearly identified and did not cross-react with other alphaviruses. Conclusion: This safe and easy to use multiplex assay allows the discrimination of alphavirus-specific reactivity within a single assay and has potential for epidemiological surveillance. It might also be useful for the development of a pan-alphavirus vaccine.

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West Nile or Usutu Virus? A Three-Year Follow-Up of Humoral and Cellular Response in a Group of Asymptomatic Blood Donors

Viruses ◽

10.3390/v12020157 ◽

2020 ◽

Vol 12 (2) ◽

pp. 157 ◽

Cited By ~ 7

Author(s):

Percivalle ◽

Cassaniti ◽

Sarasini ◽

Rovida ◽

Adzasehoun ◽

...

Keyword(s):

Differential Diagnosis ◽

Blood Transfusion ◽

Neutralizing Antibodies ◽

Cellular Response ◽

Blood Donors ◽

Cross Reactivity ◽

True Positive ◽

West Nile ◽

Usutu Virus

West Nile virus (WNV) and Usutu virus (USUV) are two related arboviruses (genus Flavivirus, family Flaviviridae), with birds as a reservoir and mosquitoes as transmitting vectors. In recent years, WNV epidemiology changed in many European countries with increased frequency of outbreaks posing the issue of virus transmission risks by blood transfusion. USUV emerged for the first time in birds of the Tuscany region (Italy) in 1996 and in 2001 in Austria. While WNV is responsible for both mild and neuroinvasive diseases, USUV infection is usually asymptomatic and neuroinvasive symptoms are rare. Since WNV and USUV co-circulate, the surveillance of WNV allows also the detection of USUV. Due to the great similarity in amino-acid sequence of major surface proteins of the two viruses, a high cross-reactivity can lead to misinterpretation of serological results. Here, we report the results obtained from 54 asymptomatic blood donors during a three-year follow-up showing an unexpected high positivity (46.3%) for USUV. The major obstacle encountered in the differential diagnosis between these two viruses was the high cross-reactivity found in neutralizing antibodies (NT Abs) and, in some cases, a long follow-up was mandatory for a correct diagnosis. Moreover, two new ELISpot assays were developed for a more rapid and specific differential diagnosis, especially in those cases in which NT Abs were not determinant. Using a combination of Enzyme-linked immunospot (ELISpot), molecular, and serological tests, we could identify 25 true positive WNV and 25 true positive USUV blood donors. Our data highlight the importance of raising awareness for increasing USUV infections in endemic countries involved in blood transfusion and organ donation.

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Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories

10.1101/2020.07.30.20165373 ◽

2020 ◽

Cited By ~ 2

Author(s):

Lene Holm Harritshoej ◽

Mikkel Gybel-Brask ◽

Shoaib Afzal ◽

Pia R. Kamstrup ◽

Charlotte Svaerke Joergensen ◽

...

Keyword(s):

Symptom Onset ◽

Blood Donors ◽

High Sensitivity ◽

Cross Reactivity ◽

Nucleic Acid Amplification ◽

Limited Data ◽

Serum Samples ◽

Diagnostic Use ◽

Ig G ◽

Abbott Architect

Serological SARS-CoV-2 assays are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for the large-volume detection of total antibodies (Ab) and immunoglobulin (Ig) G and M against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was organized as a Danish national collaboration and included fifteen commercial and one in-house anti-SARS-CoV-2 assays in sixteen laboratories. Sensitivity was evaluated using 150 serum samples from individuals diagnosed with asymptomatic, mild or moderate nonhospitalized (n=129) or hospitalized (n=31) COVID-19, confirmed by nucleic acid amplification tests, collected 13-73 days from symptom onset. Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from > 586 blood donors and patients with autoimmune diseases or CMV or EBV infections. Predefined specificity criteria of ≥99% were met by all total-Ab and IgG assays except one (Diasorin/LiaisonXL-IgG 97.2%). The sensitivities in descending order were: Wantai/ELISA total-Ab (96.7%), CUH/NOVO in-house ELISA total-Ab (96.0%), Ortho/Vitros total-Ab (95.3%), YHLO/iFlash-IgG (94.0%), Ortho/Vitros-IgG (93.3%), Siemens/Atellica total-Ab (93.2%), Roche-Elecsys total-Ab (92.7%), Abbott-Architect-IgG (90.0%), Abbott/Alinity-IgG (median 88.0%), Diasorin/LiaisonXL-IgG (84.6%), Siemens/Vista total-Ab (81.0%), Euroimmun/ELISA-IgG (78.0%), and Snibe/Maglumi-IgG (median 78.0%). The IgM results were variable, but one assay (Wantai/ELISA-IgM) had both high sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity. In conclusion, predefined sensitivity and specificity acceptance criteria of 90%/99%, respectively, for diagnostic use were met in five of six total-Ab and three of seven IgG assays.

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Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2

Journal of Clinical Microbiology ◽

10.1128/jcm.01694-20 ◽

2020 ◽

Vol 58 (10) ◽

Cited By ~ 7

Author(s):

Peter Muench ◽

Simon Jochum ◽

Verena Wenderoth ◽

Beatus Ofenloch-Haehnle ◽

Michael Hombach ◽

...

Keyword(s):

Blood Donors ◽

Diagnostic Testing ◽

High Sensitivity ◽

Cross Reactivity ◽

Point Estimates ◽

Wide Range ◽

Vesicular Stomatitis ◽

Sensitivity Specificity ◽

Development And Validation ◽

Roche Diagnostics

ABSTRACT The Elecsys Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide accurate, reliable detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, cross-reactivity, and agreement with a vesicular stomatitis virus-based pseudoneutralization assay for the Elecsys Anti-SARS-CoV-2 immunoassay. Sensitivity and agreement between Elecsys Anti-SARS-CoV-2 immunoassay and pseudoneutralization assay measurements were evaluated using samples from patients with PCR-confirmed SARS-CoV-2 infection, a majority of whom were hospitalized. Specificity was evaluated using samples from routine diagnostic testing/blood donors collected before December 2019 and thus deemed negative for SARS-CoV-2-specific antibodies. Cross-reactivity was evaluated using samples containing a wide range of potentially cross-reacting analytes, purchased from commercial vendors. For sensitivity and specificity, point estimates and 95% confidence intervals (CIs) were calculated. Agreement between the Elecsys Anti-SARS-CoV-2 immunoassay and the pseudoneutralization assay was calculated. The sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in patients with prior PCR-confirmed SARS-CoV-2 infection was 99.5% (95% CI, 97.0 to 100.0%) at ≥14 days post-PCR confirmation. Overall specificity (n = 10,453) was 99.80% (95% CI, 99.69 to 99.88%). Only 4/792 samples containing potential cross-reacting analytes were reactive with the Elecsys Anti-SARS-CoV-2 immunoassay, resulting in an overall specificity in this cohort of 99.5% (95% CI, 98.6 to 99.9%). Positive, negative, and overall agreement (n = 46) between the Elecsys Anti-SARS-CoV-2 immunoassay and the pseudoneutralization assay were 86.4% (95% CI, 73.3 to 93.6%), 100% (95% CI, 34.2 to 100%), and 87.0% (95% CI, 74.3 to 93.9%), respectively. The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated high sensitivity (99.5% at ≥14 days post-PCR confirmation) and specificity (99.80%), supporting its use as a tool for identification of past SARS-CoV-2 infection, including use in populations with low disease prevalence.

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