Clinical Significance of Molds Newly Available for Radioallergosorbent Testing

1989 ◽  
Vol 101 (1) ◽  
pp. 1-4 ◽  
Author(s):  
William P. King
Keyword(s):  
Clinical Significance ◽  
False Positive ◽  
Cross Reactivity ◽  
Significant Variance ◽  
Corpus Christi ◽  
Airborne Allergen

Three years of weekly Rotorod airborne allergen reports from Corpus Christi, Texas, were reviewed. Five of 10 newly available airborne molds for radioallergosorbent testing (RAST) were present in significant numbers. Three hundred seventy-five mold RAST evaluations were expanded to include the five old and these five new molds. Except for Alternaria, the frequency of and allegenic response to the new molds were generally greater than those for the five old molds. The usual Alternaria-Cladosporium mold screen proved less satisfactory when these five new molds were added to the mold battery; however, the addition of Helminthosporium to the screen corrected this deficiency. Cross-reactivity production of false-positive responses seems unlikely because of frequent significant variance in RAST scores from mold to mold in the same patient.

scholarly journals Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

2016 ◽  
Vol 54 (6) ◽  
pp. 1566-1572 ◽  
Author(s):  
Alba Abras ◽  
Montserrat Gállego ◽  
Teresa Llovet ◽  
Silvia Tebar ◽  
Mercedes Herrero ◽  
...  
Keyword(s):  
Chagas Disease ◽  
False Positive ◽  
Disease Diagnosis ◽  
Cross Reactivity ◽  
Human Migration ◽  
Serological Diagnosis ◽  
Content Type ◽  
New Generation ◽  
Single Technique ◽  
Chronic Chagas Disease

Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity withLeishmaniaspp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity withLeishmaniaspecies. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.

scholarly journals Do intestinal parasites interfere with the seroepidemiologic surveillance of Schistosoma mansoni infection?

1996 ◽  
Vol 116 (3) ◽  
pp. 323-329 ◽  
Author(s):  
B. Alarcón De Noya ◽  
C. Colmenares ◽  
S. Losada ◽  
Z. Fermin ◽  
G. Masroua ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
False Positive ◽  
Total Population ◽  
Intestinal Parasites ◽  
Field Work ◽  
Cross Reactivity ◽  
Cross Reaction ◽  
Protein Fractions ◽  
Egg Antigen ◽  
Immunoenzymatic Assay

SUMMARYIn view of the known cross-reactivity of sera from patients with intestinal parasites to some Schistosoma mansoni antigens, field work was conducted in an area of Venezuela non-endemic for schistosomiasis using the routine immunoenzymatic assay (ELISA) with soluble egg antigen (SEA). False positive reactions represented 15·3% of the total population as determined by SEA–ELISA. SEA-immunoblotting of the false positive sera indicated that protein fractions of 91 and 80 kDa appear to be responsible for cross-reactivity. Sera from hookworm infected individuals produced a higher frequency and intensity of cross-reaction than other sera. SEA-fractions of 105, 54, 46, 42, 32, 25 and 15 kDa were the most specific.

scholarly journals Potential Antigenic Cross-reactivity Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Dengue Viruses

2020 ◽  
Author(s):  
Yaniv Lustig ◽  
Shlomit Keler ◽  
Rachel Kolodny ◽  
Nir Ben-Tal ◽  
Danit Atias-Varon ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Envelope Protein ◽  
False Positive ◽  
In Silico ◽  
Rapid Test ◽  
Cross Reactivity ◽  
Lateral Flow ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Elisa Testing

Abstract Background Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity. Methods We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities. Results Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID-19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E−5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E−4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein. Conclusions Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health.

scholarly journals Wisconsin’s Screening Algorithm for the Identification of Newborns with Congenital Adrenal Hyperplasia

2019 ◽  
Vol 5 (3) ◽  
pp. 33 ◽  
Author(s):  
Eric R. Bialk ◽  
Michael R. Lasarev ◽  
Patrice K. Held
Keyword(s):  
Birth Weight ◽  
Congenital Adrenal Hyperplasia ◽  
False Positive ◽  
False Positive Rate ◽  
Cross Reactivity ◽  
Adrenal Hyperplasia ◽  
Screening Assay ◽  
Study Results ◽  
Second Tier ◽  
17 Hydroxyprogesterone

Newborn screening for congenital adrenal hyperplasia (CAH) has one of the highest false positive rates of any of the diseases on the Wisconsin panel. This is largely due to the first-tier immune assay cross-reactivity and physiological changes in the concentration of 17-hydroxyprogesterone during the first few days of life. To improve screening for CAH, Wisconsin developed a second-tier assay to quantify four different steroids (17-hydroxyprogesterone, 21-deoxycortisol, androstenedione, and cortisol) by liquid chromatography–tandem mass spectrometry (LC–MSMS) in dried blood spots. From validation studies which included the testing of confirmed CAH patients, Wisconsin established its own reporting algorithm that incorporates steroid concentrations as well as two different ratios—the birth weight and the collection time—to identify babies at risk for CAH. Using the newly developed method and algorithm, the false positive rate for the CAH screening was reduced by 95%. Patients with both classical forms of CAH, salt-wasting and simple virilizing, were identified. This study replicates and expands upon previous work to develop a second-tier LC–MSMS steroid profiling screening assay for CAH. The validation and prospective study results provide evidence for an extensive reporting algorithm that incorporates multiple steroids, birth weight, and collection times.

Cross-reactivities of cyclosporin G (NVa2 cyclosporin) and metabolites in cyclosporin A immunoassays

1993 ◽  
Vol 39 (6) ◽  
pp. 1089-1092 ◽  
Author(s):  
R W Yatscoff ◽  
L J Langman ◽  
D F LeGatt
Keyword(s):  
Cyclosporin A ◽  
Enzyme Immunoassay ◽  
Fluorescence Polarization ◽  
Cross Reactivity ◽  
Fluorescence Polarization Immunoassay ◽  
Total Drug ◽  
Significant Variance ◽  
Routine Monitoring ◽  
The Cross

Abstract Immunoassays of cyclosporin A (CsA) have been routinely used to measure CsG. We investigated the cross-reactivities of CsG and its metabolites, as well as the proportion CsG constitutes in relation to total drug measured, for six CsG metabolites (GM1, GM9, GM4N, GM1c, GM1c9, GM19) in the following CsA assays: Sandimmune selective RIA (SS), Sandimmune nonselective RIA (NS), Cyclotrac SP-RIA (CT), fluorescence polarization immunoassay (FPIA), and enzyme immunoassay (EMIT). The cross-reactivity of CsG in these assays was as follows: SS, FPIA, CT, approximately 100%; NS, approximately 40%; EMIT, &lt; 2%. The cross-reactivities of CsG metabolites were investigated in all assays except EMIT and varied among metabolites and assays. The most significant variance was found with the NS assay, where most of the metabolites exhibited cross-reactivities of &gt; 40%. In contrast, in the SS, FPIA, and CT assays, cross-reactivities of &lt; 5% were observed for most of the metabolites. The ranking of cross-reactivities of CsG metabolites in the assays is SS = CT &lt; FPIA &lt; NS. The degree of cross-reactivity did not change significantly when the SS, CT, and FPIA assays were calibrated with CsG instead of CsA--whether parent CsG was present or not. The data suggest that the SS, CT, and FPIA methods would be suitable for the routine monitoring of CsG.

Kavain Interference with Amphetamine Immunoassay

2020 ◽  
Author(s):  
H Madhavaram ◽  
T Patel ◽  
C Kyle
Keyword(s):  
False Positive ◽  
Cross Reactivity ◽  
Drug Prevention ◽  
Urine Samples ◽  
Gas Chromatography Mass Spectrometry ◽  
Piper Methysticum ◽  
Fragmentation Pattern ◽  
Aboriginal Communities ◽  
Australian Aboriginal ◽  
Positive Urine

Abstract We encountered unexpected false-positive urine results in three patients for amphetamine-type substances by immunoassay (IA), measured as part of community drug prevention programs. Kavain was identified in all three urine samples by gas chromatography-mass spectrometry (GC-MS). No other potential cross-reactants were found. Kavain is a kava-lactone present in kava, a ceremonial and recreational drink derived from the roots and stems of the plant Piper methysticum. It is consumed regularly by many indigenous Pacific and Australian Aboriginal communities. Urine IA was performed on a Beckman Coulter AU480 Analyzer using cloned enzyme donor immunoassay (CEDIA) amphetamine-type substance reagent and DRI ethanol reagent. We purchased three different kava powders from local kava clubs and dissolved in ethanol, then evaporated and reconstituted in blank urine and analyzed by IA, GC-MS for amphetamine-type substances. Additionally, authentic kavain standard was also tested for cross-reactivity by IA and analyzed by GC-MS to compare the mass fragmentation pattern and retention time with the kava powder and patient specimens. The patient urine samples tested positive by CEDIA IA for amphetamines. However, when analyzed by GC-MS, they were negative for amphetamine-type but contained kavain. The kava powders and kavain standard all cross-reacted with the amphetamine IA to give falsely detected results. GC-MS did not identify any amphetamine-type compounds in any of the kava powders nor in the kavain standard. To our knowledge, this is the first report of false-positive amphetamine measurements due to kavain, a component of the kava drink, widely consumed in Oceania and Australasia.

Outbreak or illusion: consequences of ‘improved’ diagnostics for gonorrhoea

2016 ◽  
Vol 28 (7) ◽  
pp. 667-671 ◽  
Author(s):  
Amy Bennett ◽  
Katie Jeffery ◽  
Eunan O’Neill ◽  
Jackie Sherrard
Keyword(s):  
False Positive ◽  
Cross Reactivity ◽  
Practical Reasons ◽  
Predictive Values ◽  
Confirmatory Testing ◽  
Neisseria Species ◽  
Sexual Health Service ◽  
Sex With Men ◽  
A Prospective Study ◽  
Low Prevalence

The sexual health service in Oxford introduced gonorrhoea nucleic amplification acid testing using the BD Viper XTR™ System. For practical reasons, a confirmatory nucleic amplification acid testing using a different platform was not used initially. Following the introduction of nucleic amplification acid testing, the rates of gonorrhoea increased threefold. Concerns were raised that this increase represented an outbreak. A retrospective review of cases over six months suggested that there may have been a number of false-positive results. A prospective study was then undertaken over six months, where all gonorrhoea positive samples were sent for confirmatory testing. This evaluation of all gonorrhoea cases in an English county found that the overall presumptive false-positive rates for gonorrhoea nucleic amplification acid testing using BD Viper XTR™ in our population are significant at 27% of female samples, 13.2% of heterosexual male samples, 3.5% of anogenital multiple site men who have sex with men samples and 62.8% of pharyngeal only men who have sex with men samples. The data demonstrate the need for confirmatory testing using a second nucleic acid target, as per BASHH/Public Health England guidelines, especially in low-prevalence settings and extragenital sites, due to cross-reactivity with commensal Neisseria species and low positive predictive values.

scholarly journals Characterization of Human and Murine Anti-Protamine/Heparin Antibodies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3461-3461 ◽  
Author(s):  
Grace M. Lee ◽  
Manali Joglekar ◽  
Sanjay Khandelwal ◽  
Rui Qi ◽  
Lubica Rauova ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Cross Reactivity ◽  
Neutrophil Activation ◽  
Nuclear Proteins ◽  
Platelet Factor ◽  
Isotype Control ◽  
Nuclear Antigens ◽  
Control Plasma

Abstract Protamine/heparin (PRT/H) antibodies (Abs) are a newly described class of heparin-dependent antibodies found in ~25% of patients exposed to protamine and heparin during cardiopulmonary bypass surgery (CPB). Although recent studies show that PRT/H Abs have several serologic properties similar to platelet factor 4 (PF4)/heparin Abs, the clinical significance of PRT/H Abs is unknown. To understand their clinical significance, we undertook studies to characterize the biologic effects of PRT/H Abs in vitro. Using a previously described murine monoclonal antibody to PRT/H complexes (IgG3 isotype, ADA) and patient-derived PRT/H Abs, we examined antibody cross-reactivity with histones and nuclear proteins as well as functional effects of PRT/H Abs on neutrophil activation. Using a commercial ANA immunofluorescence assay (ImmuGlow Hep-2 Cells Anti-nuclear Antibody IFA kit), we first examined cross-reactivity of anti-PRT/H on nuclear proteins. As seen in Figure 1, both ADA and patient-derived PRT/H Abs (depicted as α-PRT/H (+) in Figure 1D) showed significant binding to Hep-2 cells. In contrast, no reactivity was seen when Hep-2 cells were incubated with plasma from CPB patients who were seronegative for PRT/H antibodies (depicted as α-PRT/H (-) in Figure 1D) or with IgG3 isotype (data not shown). To confirm that PRT/H Abs were binding to nuclear antigens, we examined the cross-reactivity of monoclonal and polyclonal anti-PRT/H on individual nuclear binding proteins, including Single Stranded Binding Protein, RO-52, JO-1, (Sigma; St. Louis, MO, USA) and nucleosomes (New England Biolabs; UK) by ELISA. As shown in Table 1, ADA showed significantly higher binding to all nuclear antigens as compared to isotype control. Polyclonal PRT/H Abs from CPB patients also showed increased binding to nuclear antigens relative to control plasma, but did not achieve statistical significance. To determine if PRT/H Abs activate neutrophils, we isolated neutrophils by gradient centrifugation and incubated cells with 100 ug/mL of ADA or isotype in the presence or absence of antigen (PRT 31 ug/mL + H4 U/mL) and measured release of myeloperoxidase (MPO). As shown in Figure 2, ADA alone or isotype control showed minimal MPO release. In the presence of PRT or PRT/H, ADA, but not isotype control, showed significant MPO release. Taken together, these studies demonstrate that PRT/H Abs cross-react with nuclear antigens and can trigger neutrophil activation. These findings suggest that PRT/H Abs cross-react with a closely related class of antigens (histones) and enhance inflammation through cross-reactivity with nuclear antigens and/or through functional effects on neutrophil activation. Table 1. Antibody SSBP RO52 JO-1 nucleosomes ADA v. Isotype 1.36 ± 0.06 v. 0.13 ± 0.01 1.76 ± 0.06 v. 0.08 ± 0.01 1.64 ± 0.03 v. 0.09 ± 0.01 0.73 ± 0.03 v. 0.07 ± 0.01 Polyclonal PRT/H Abs v. control plasma 1.01 ± 0.23 v. 0.54 ± 0.05 1.15 ± 0.21 v. 0.72 ± 0.02 0.92 ± 0.16 v. 0.49 ± 0.04 0.81 ± 0.14 v. 0.75 ± 0.3 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Robustness of Serologic Investigations for Chikungunya and Mayaro Viruses following Coemergence

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Carlo Fischer ◽  
Fernando Bozza ◽  
Xiomara Jeanleny Merino Merino ◽  
Celia Pedroso ◽  
Edmilson F. de Oliveira Filho ◽  
...  
Keyword(s):  
Latin America ◽  
False Positive ◽  
Chikungunya Virus ◽  
Cross Reactivity ◽  
Positive Test ◽  
Antibody Detection ◽  
Test Results ◽  
Specific Patient ◽  
False Positive Test ◽  
Mayaro Virus

ABSTRACT Since 2013, the arthropod-borne Chikungunya virus (CHIKV) has cocirculated with the autochthonous Mayaro virus (MAYV) in Latin America. Both belong to the same alphavirus serocomplex, termed the Semliki Forest serocomplex. The extent of antibody cross-reactivity due to the antigenic relatedness of CHIKV and MAYV in commonly used serologic tests remains unclear. By testing 64 CHIKV- and 37 MAYV-specific sera from cohort studies conducted in Peru and Brazil, we demonstrate about 50% false-positive test results using commercially available enzyme-linked immunosorbent assays (ELISAs) based on structural antigens. In contrast, combining ELISAs for CHIKV and MAYV significantly increased positive predictive values (PPV) among all cohorts from 35.3% to 88.2% for IgM and from 61.3% to 96.8% for IgG (P < 0.0001). Testing of longitudinally collected CHIKV-specific patient sera indicated that ELISA specificity is highest for IgM testing at 5 to 9 days post-onset of symptoms (dpo) and for IgG testing at 10 to 14 dpo. IgG cross-reactivity in ELISA was asymmetric, occurring in 57.9% of MAYV-specific sera compared to 29.5% of CHIKV-specific sera. Parallel plaque reduction neutralization testing (PRNT) for CHIKV and MAYV increased the PPV from 80.0% to 100% (P = 0.0053). However, labor-intense procedures and delayed seroconversion limit PRNT for patient diagnostics. In sum, individual testing for CHIKV or MAYV only is prone to misclassifications that dramatically impact patient diagnostics and sero-epidemiologic investigation. Parallel ELISAs for both CHIKV and MAYV provide an easy and efficient solution to differentiate CHIKV from MAYV infections. This approach may provide a template globally for settings in which alphavirus coemergence imposes similar problems. IMPORTANCE Geographically overlapping transmission of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in Latin America challenges serologic diagnostics and epidemiologic surveillance, as antibodies against the antigenically related viruses can be cross-reactive, potentially causing false-positive test results. We examined whether widely used ELISAs and plaque reduction neutralization testing allow specific antibody detection in the scenario of CHIKV and MAYV coemergence. For this purpose, we used 37 patient-derived MAYV-specific sera from Peru and 64 patient-derived CHIKV-specific sera from Brazil, including longitudinally collected samples. Extensive testing of those samples revealed strong antibody cross-reactivity in ELISAs, particularly for IgM, which is commonly used for patient diagnostics. Cross-neutralization was also observed, albeit at lower frequencies. Parallel testing for both viruses and comparison of ELISA reactivities and neutralizing antibody titers significantly increased diagnostic specificity. Our data provide a convenient and practicable solution to ensure robust differentiation of CHIKV- and MAYV-specific antibodies.

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